Leukemia Committee Agenda - SWOG 2002/Leukemia.pdfDr. Schiffer Proposed Studies S0106 TMA Phase III...

APRIL 19 - 21, 2002 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 1

LEUKEMIA COMMITTEE

Chair: Frederick R. Appelbaum, M.D. Vice Chair: David R. Head, M.D.

Statisticians: Kenneth J. Kopecky, Ph.D.

Holly Gundacker, M.S.

Data Coordinator: Laura Kingsbury, M.R.T. Protocol Coordinator: Larissa Rios, B.A.

Pathology: David R. Head, M.D.

Cytogenetics Liaison: Marilyn L. Slovak, Ph.D.

Nurse: Rose B. Ermete, R.N. O.C.N.

Clinical Research Associate:

Emilia G. Cantu, B.A.

2 LEUKEMIA SOUTHWEST ONCOLOGY GROUP APRIL 19 - 21, 2002

CONTENTS Leukemia Committee Agenda . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

Initial Registrations to Therapeutic Studies . . . . . . . . . . . . . . . . . . . . . 5

Patient Registration by Study and Arm . . . . . . . . . . . . . . . . . . . . . . . 6

C19801 Phase II Intergroup. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

C9710 Phase III Intergroup . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

E2998 Phase III Intergroup . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

S9007 Biologic Intergroup . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

S9910 Biologic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

S0010 Phase II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

S0020 Phase II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

S0106 Phase III . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

S0112 Phase II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

S0117 Phase II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24

S0125 Phase II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25


Leukemia Committee Agenda

Introductory Remarks

Current Status of the Leukemia Committee Dr. Appelbaum

Status of AML/MDS Studies

Active and Closed Studies

C9710 Phase III Randomized Study of Concurrent Tretinoin and Chemotherapy with or without Arsenic Trioxide (As2O3) (NSC #706363) as Initial Consolidation Therapy Followed by Maintenance Therapy with Intermittent Tretinoin Versus Intermittent Tretinoin Plus Mercaptopurine and Methotrexate for Patients with Untreated Acute Promyelocytic Leukemia.

Dr. Coutre

E2998 A Phase III Study of Flt3 Ligand (Flt3L) Therapy in Acute Myeloid Leukemia (AML) Patients in Remission.

Dr. Godwin

S0112 A Phase II Study of Daunomycin and Ara-C, Both Given by Continuous IV Infusion for Previously Untreated Non-M3 Acute Myeloid Leukemia (AML) in Patients of Age 56 or Older.

Dr. Chauncey

S0020 A Phase II Study of Anti-Thymocyte Globulin and Cyclosporine for Patients with Myelodysplastic Syndrome (MDS). Dr. Schiffer

Proposed Studies

S0106 A Phase III Study of Gemtuzumab Ozogamicin (MylotargTM) as Post-Consolidation Therapy for Patients Under Age 56 with Previously Untreated Acute Myeloid Leukemia (AML).

Dr. Petersdorf

S0117 A Phase II Study of Gemtuzumab Ozogamicin (MylotargTM) and Standard Dose Ara-C for Patients with Relapsed Acute Myeloid Leukemia (AML).

Dr. Godwin

S0125 A Phase II Study of Chimerism-Mediated Immunotherapy (CMI) Using Nonmyeloablative Allogeneic Transplantation in Older Patients with Acute Myeloid Leukemia (AML) in First Complete Remission.

Dr. McSweeney

Status of CML Studies

Proposed Studies

SWOG Coordinated Intergroup Gleevec Trial. Drs. Drucker and Appelbaum

Miscellaneous Studies

Novartis 106: Gleevec Versus Interferon + Ara-C. Dr. Appelbaum


Status of ALL Studies


C19801 A Phase II Study of 506U78 in Patients with Refractory or Relapsed T-Lineage Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma (LBL).

Dr. Coutre

S0010 A Phase II Trial of 506U78 (IND 52611) in Patients with Relapsed or Refractory Non T-Cell Acute Lymphoblastic Leukemia (ALL).

Dr. Coutre

Proposed Studies

S0100 Frontline ALL Study. Dr. Forman

C10001 A Phase II Trial of Sequential Chemotherapy, Imatinib Mesylate (Gleevec, STI571) (NSC #716051, IND #61135), and Transplantation for Adults with Newly Diagnosed Ph+ Acute Lymphoblastic Leukemia by the CALGB and SWOG.

Drs. Appelbaum and Radich

Status of CLL Studies

Proposed Studies

E2997 Phase III Randomized Trial of Fludarabine and Cyclophosphamide versus Fludarabine for Previously Untreated Chronic Lymphocytic Leukemia

Dr. Hussein

Status of Other Studies


S9007 Cytogenetic Studies in Leukemia Patients. Dr. Slovak

S9910 Leukemia Centralized Reference Laboratories and Tissue Repositories, Ancillary.

Dr. Willman


Initial Registrations to Therapeutic Studies

by 12 month Intervals LEUKEMIA COMMITTEE

0

50

100

150

200

250

300

Time of registration

JAN 1997DEC 1997

145

41

87

4

JAN 1998DEC 1998

100

32

87

1

JAN 1999DEC 1999

32

11

27

JAN 2000DEC 2000

21

7

30

JAN 2001DEC 2001

188

34

MEMBER AFFILIATES CCOP NON-SWOG


Patient Registration by Study and Arm LEUKEMIA COMMITTEE

July-Dec

2001 Jan-June 2001 July-Dec

2000 All Patients

C19801 T-ALL/LBL, Rel/Refr., 506U78 * 506U78 4 6 1 11 C9710 APL, ATRA +/- Arsenic Trioxide * Induction

Induction/Consolidation 7 4 8 27 Induction/Consolidation w/Arsenic 6 5 2 21 13 9 10 48 E2998 AML, Remission, Flt3L vs Obs. * Randomization

Flt3L 1 0 1 2 Observation 0 1 0 1 1 1 1 3 S9007 Cytogenetic Studies in Leukemia Patients Cytogenetics Sample 35 17 17 2,046 S9910 Leukemia Central Lab/Tissue Repository Specimen Submission 32 19 17 103 S9918 AML, Ara-C/DNR/PSC833, Age 56+ Ara-C/DNR/PSC-833 0 0 5 18 S9920 MDS/MDS-AML BU-TBI vs CY-TBI BU-TBI 0 0 0 0 CY-TBI 0 1 0 1 0 1 0 1 S0010 Non-T-ALL, Rel/Refr., 506U78 506U78 4 6 0 10 S0020 MDS, ATG + Cyclosporine ATG + Cyclosporine 4 0 0 4 S0112 AML, DNR/Ara-C cont infusion Induction

DNR/Ara-C 11 0 0 11

* For non-SWOG coordinated studies only SWOG registrations are shown.


C19801/II

C19801 Phase II Intergroup Coordinating Group: CALGB

A Phase II Study of 506U78 in Patients with Refractory or Relapsed T-Lineage Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic

Lymphoma (LBL)

Intergroup Participants: CALGB, SWOG

Study Coordinators: D DeAngelo (CALGB), S Coutre, A Stopeck

Statisticians: H Gundacker, K Kopecky

Data Coordinator: L Kingsbury

Date Activated: 6/15/2000

Date Closed: 9/12/2001

Objectives To determine the complete and partial remission rates, as well as the remission duration, in patients with refractory or relapsed T-lineage acute lymphoblastic leukemia or lymphoblastic lymphoma receiving 506U78 (1.5 gram/m²/day) on an alternate day schedule (days 1,3,5).

To determine the safety and toxicity associated with 506U78 administered on this schedule to patients with refractory or relapsed T-lineage acute lymphoblastic leukemia or lymphoblastic lymphoma.

Patient Population Patients must have a histologic diagnosis of T-lineage acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL). Leukemia or lymphoma cells should express at least two of the following cell surface antigens: CD1a, CD2, CD3 (surface or cytoplasmic), CD4, CD5, CD7, and CD8. Leukemia cells should also be negative for myeloperoxidase or Sudan Black B. If the only T cell markers present are CD4 and CD7, the leukemic cells should be demonstrated to lack the myeloid markers, CD33 and/or CD13. Patients must not have CNS leukemia or lymphoma requiring intrathecal or craniospinal radiation therapy.

Patients must be refractory to at least one induction treatment regimen or in first or later relapse after achieving a complete remission.

Patients must not have a history of a seizure disorder, neurologic toxicity of ≥ Grade 3 during

prior treatment of ALL/LBL, or pre-existing neuropathy ≥ Grade 2 at the time of registration regardless of causality. Patients must have adequate hepatic and renal function, and must be ≥ age 16.

Accrual Goals Initially, 18 evaluable patients will be accrued. If fewer than three patients achieve CR then the study will be closed. Otherwise, 17 additional evaluable patients will be accrued for a total of 35 patients.

Summary Statement This study opened to accrual in CALGB on August 15, 1998 and in SWOG on June 15, 2000. The study closed to accrual on September 12, 2001 with a total of 40 patients registered, including 11 from SWOG institutions.

Toxicities of Grade 3 or higher were reported for 30 evaluable patients in the November 2001 CALGB report. No fatal toxicities or Grade 4 non-hematologic toxicities were reported. The reported Grade 3 non-hematologic toxicities are as follows: five patients with fatigue, two with febrile neutropenia, and one each with hypertension, infection, hallucinations, seizures, confusion, diarrhea, muscle weakness, myalgia, tumor lysis syndrome, and increased bilirubin.

The complete November, 2001 summary of this study from CALGB is available on the Southwest Oncology Group web site.


C19801/II

Registration by Institution

Institutions Total Reg Institutions

Total Reg

Stanford University/City of Hope Med Ctr 2 Oregon Hlth Sci Univ 1

Arizona, U of 1 Puget Sound 1 City of Hope Med Ctr 1 South Alabama CCOP 1 Columbus CCOP 1 Wichita CCOP 1 Loyola University 1 Total (10 Institutions) 11 New Mexico MBCCOP 1


C9710/III

C9710 Phase III Intergroup Coordinating Group: CALGB

Phase III Randomized Study of Concurrent Tretinoin and Chemotherapy with or without Arsenic Trioxide (As2O3) (NSC #706363) as Initial

Consolidation Therapy Followed by Maintenance Therapy with Intermittent Tretinoin Versus Intermittent Tretinoin Plus Mercaptopurine and

Methotrexate for Patients with Untreated Acute Promyelocytic Leukemia

Intergroup Participants: CALGB, SWOG, COG, ECOG, NCIC

Study Coordinators: B Powell (CALGB), S Coutre, M Tallman (ECOG), S Couban (NCIC), J Feusner (COG)




Schema

RANDOMIZE

CR or PR*ATRA + Ara-C+ DNR

As 2O3

ATRA + 6-MP/MTX for 1 Year

RANDOMIZE ATRA for 1 Year

ATRA + DNR

INDUCTION

ATRA + Ara-C+ DNR

CONSOLIDATIONTHERAPY

CR

MAINTENANCE THERAPY

*Patients who fail to achieve CR or PR after Induction Therapy are removed from protocol treatment.

Objectives To compare the efficacy (event-free survival) and toxicities of two induction/consolidation therapies for patients with untreated APL: ATRA/Ara-C/daunorubicin with or without arsenic trioxide (As2O3).

To evaluate the efficacy (disease-free survival) and toxicities of maintenance therapy with intermittent ATRA vs intermittent ATRA plus 6-

MP/MTX for patients with APL who achieve a complete response.

To explore the relationship between CD56 expression at diagnosis and clinical outcomes.

To evaluate the cardiac toxicity of intensive daunorubicin therapy, as given in this study, to pediatric patients.


C9710/III

Patient Population Patients must have a clinical diagnosis of acute promyelocytic leukemia (APL) with proof of APL morphology (FAB-M3) confirmed by RT-PCR assay. A patient may be entered prior to completion of RT-PCR studies, but a patient who is subsequently found to be PML-RARα negative and RARα-PML negative will be removed from protocol treatment.

Patients must not have received any systemic definitive treatment for APL, including cytotoxic chemotherapy or retinoids. Prior therapy with corticosteroids, hydroxyurea or leukapheresis is allowed.

Accrual Goals The accrual goal for this study is 420 patients.

Summary Statement This study opened to accrual in CALGB on June 15, 1999, and in SWOG on July 15, 1999. On May 1, 2001, the protocol was amended (Update #5) to change the randomization for the maintenance phase of therapy. There is no longer an "Observation" arm. The new randomization is between ATRA and ATRA + Chemotherapy.

Effective July 15, 2001, institutions without IRB approval of Update #5 are not able to register patients to the protocol.

As of December 31, 2001, a total of 172 patients have registered to this study, including 48 from SWOG institutions.

Based on the CALGB report of November 2001, a total of 76 patients have been evaluated for induction toxicity, including 64 registered from adult institutions (CALGB, ECOG, SWOG). There have been no fatal toxicities among these 76 patients. Toxicities of Grade 4 were reported for 17 of the 51 patients including 11 from adult institutions. The Grade 4 non-hematologic toxicities included two reports of hepatic toxicity, and one report each of stomatitis/pharyngitis, infection, dyspnea, and myositis for patients from adult institutions; and three reports of infection and one report of decreased fibrinogen for patients from pediatric institutions.

The complete November, 2001 summary of this study from CALGB is available on the Southwest Oncology Group web site.

Registration by Institution Registrations ending December 31, 2001


Total Reg

Columbus CCOP 8 Puget Sound 2 Atlanta Reg CCOP 4 Sutter Hlth Western/Davis, U of CA 2 Loyola University 3 Upstate Carolina 2 Stanford University/City of Hope Med Ctr 3 Columbia River CCOP 1 Wichita CCOP 3 Michigan, U of 1 Central IL CCOP 2 Providence Hosp 1 Cleveland Clinic OH 2 Scott & White CCOP 1 Davis, U of CA 2 Thompson Ca Surv Ctr/San Antonio, U of TX 1 Grand Rapids CCOP 2 Tulane University 1 Mississippi, U of 2 Wayne State Univ 1 Montana CCOP 2 Total (22 Institutions) 48 New Mexico MBCCOP 2


E2998/III

E2998 Phase III Intergroup Coordinating Group: ECOG

A Phase III Study of Flt3 Ligand (Flt3L) (NSC# 696599) Therapy in Acute Myeloid Leukemia (AML) Patients in Remission

Intergroup Participants: ECOG, SWOG, CALGB

Study Coordinators: J Rowe (ECOG), J Godwin, R Larson (CALGB)




Date Closed: 10/1/2001

Schema

RANDOMIZE

Flt3L(6 cycles)

Observation

Objectives To compare Flt3L maintenance therapy to observation only with respect to failure free survival.

To compare overall survival of patients in both arms.

To compare Flt3L administration to observation only with respect to the long-term immunologic effects on patients with AML in remission.

To evaluate the long-term safety and toxicity of extended administration of Flt3L in AML patients in remission.

Patient Population Patients must have morphologically proven diagnosis of AML or refractory anemia with excess blasts in transformation (RAEB-T), and must be in complete remission (CR).

Patients must not have received immunotherapy during their most recent treatment or allogeneic BMT.

Patients must be ≥ 18 years of age (≥60 years old if in first CR) and must have an ECOG performance status of 0-2. Patients must not have clinically significant cardiac or pulmonary disease and must have adequate hepatic and renal function. Patients must be registered to this study and start on treatment within four weeks of documentation of CR following induction therapy or within four weeks following post-remission therapy.

Stratification/Descriptive Factors Patients are stratified by (1) CR: first CR vs second CR vs third or subsequent CR; (2) any post-remission therapy: no vs yes.

Accrual Goals A total of 126 eligible patients will be accrued to this study.

Summary Statement This study opened to accrual in ECOG on July 19, 2000, and in SWOG on August 15, 2000. On May 1, 2001 the protocol was amended to include patients in first CR of age ≥60. The study closed


E2998/III

to accrual on October 1, 2001 as a result of Immunex's decision to end their financial support and discontinue additional drug supply of Flt3L. A total of 16 patients were registered, including three from SWOG institutions.

The complete November, 2001 summary of this study from ECOG is available on the Southwest Oncology Group web site.

Registration by Institution

Institutions Total Reg

Atlanta Reg CCOP 1Loyola University 1Sutter Hlth Western/Davis, U of CA 1Total (3 Institutions) 3


S9007/BIOLOGIC

S9007 Biologic Intergroup Coordinating Group: SWOG

Cytogenetic Studies in Leukemia Patients

Intergroup Participants: SWOG, ECOG

Study Coordinators: M Slovak, E Paietta (ECOG)




Objectives To estimate the frequencies and prognostic significance of cytogenetic abnormalities in marrow or blood cells of leukemia patients prior to treatment on Southwest Oncology Group protocols and at various times in the course of their treatment.

To estimate correlations between the presence of cytogenetic features and of clinical, pathophysiological, cellular, or molecular characteristics in these patients.

To provide quality control for all SWOG cytogenetic data.

Patient Population Patients must be registered to any SWOG leukemia protocol approved after January 1, 1990, including ECOG patients registered to S9300.

Summary Statement As of December 31, 2001, a total of 2046 patients was registered on this study. ECOG participated in this study from August 15, 1995 through April 8, 1998.


S9007/BIOLOGIC



Total Reg

Wichita CCOP 119 Cincinnati MC, U of 21 LSU-Shreveport 79 Columbia River CCOP 21 Loyola University 76 Breslin Cancer Ctr/Henry Ford Hosp 20 Ohio State U 76 St Francis/Stormont/Kansas, U of 20 Puget Sound 73 Kaiser Foundatn Hosp/Davis, U of CA 19 City of Hope Med Ctr 62 Montana CCOP 19 Columbus CCOP 61 Oklahoma, Univ of 18 Wayne State Univ 58 Riverside Methodist/Ohio State U 17 Cleveland Clinic OH 51 Michigan, U of 15 Davis, U of CA 48 BAMC/WHMC 14 Henry Ford Hosp 47 Kentucky, U of 14 St Louis University 46 Carilion Medical Ctr/Temple University 13 Kansas City CCOP 44 ECOG 13 St Louis CCOP 43 Oregon Hlth Sci Univ 13 San Antonio, U of TX 40 Temple University 13 Arkansas, U of 35 Allegheny CCOP 12 Atlanta Reg CCOP 32 Grand Rapids CCOP 12 Upstate Carolina 32 Michael Reese Hosp/Oklahoma, Univ of 12 Dayton CCOP 31 Northwest CCOP 12 Utah, U of 31 Providence Hosp 12 New Mexico, U of 30 Tulane Univ/San Antonio, U of TX 11 Arizona, U of 29 Akron Gen Med Ctr/Cleveland Clinic OH 10 Colorado, U of 29 Aultman Hospital/Ohio State U 10 Central IL CCOP 28 Sutter Hlth Western/Davis, U of CA 10 So Calif, U of 27 Hawaii CCOP, Univ of 9 South Alabama CCOP 25 Salem Hospital/Oregon Hlth Sci Univ 9 Scott & White/TX A&M 24 Texas Tech Univ/San Antonio, U of TX 9 Stanford University/City of Hope Med Ctr 24 Hawaii, U of 8 Mississippi, U of 23 Santa Rosa Mem Hosp/Davis, U of CA 8 Boston Univ Med Ctr 22 Thompson Ca Surv Ctr/San Antonio, U of TX 8 LSU-New Orleans CCOP 22 All Other Institutions 255 Virginia Mason CCOP 22 Total (167 Institutions) 2,046


S9910/BIOLOGIC

S9910 Biologic

Leukemia Centralized Reference Laboratories and Tissue Repositories, Ancillary

Study Coordinators: C Willman, D Boldt




Objectives To develop and apply laboratory assays for the rapid and precise diagnosis of leukemia patients and identify biologic, genetic, and molecular parameters that distinguish different subtypes of human leukemia with differing responses to therapy.

To develop "risk-adapted" therapeutic approaches in which biologic, genetic, and molecular parameters are used to target individual patients to tailored therapeutic regimens, or, to randomize and stratify patients to different treatment arms of a therapeutic trial.

To develop new automated and standardized laboratory methods for the detection and monitoring of therapeutic responsiveness and minimal residual disease in leukemia patients and develop new clinical approaches to employ such data in therapeutic decision making and clinical trial design.

To maintain and expand tissue repositories of highly characterized leukemia samples from uniformly treated Southwest Oncology Group patients to promote Intergroup and external fundamental scientific collaborations and to perform continued critical prospective and retrospective correlative biologic studies.

To utilize scientific information generated from Intergroup and collaborative studies to assist the Leukemia Committee in the development of new and more effective treatment regimens.

Patient Population Patients must be registered on a SWOG treatment study for lymphoid leukemia (ALL or CLL), myeloid leukemia (AML or CML) or myelodysplasia on or after the date of activation of this study.

Summary Statement As of December 31, 2001, 103 patients have been registered to this study.


S9910/BIOLOGIC



Total Reg

Wichita CCOP 17 LSU-Shreveport 2 Columbus CCOP 12 Ozarks Reg CCOP 2 Stanford University/City of Hope Med Ctr 9 St Louis CCOP 2 Loyola University 7 Upstate Carolina 2 New Mexico MBCCOP 5 Akron Gen Med Ctr/Cleveland Clinic OH 1 Arizona, U of 4 Columbia River CCOP 1 Atlanta Reg CCOP 4 Henry Ford Hosp 1 Puget Sound 4 Michigan, U of 1 San Antonio, U of TX 4 Oregon Hlth Sci Univ 1 Davis, U of CA 3 Providence Hosp 1 Mississippi, U of 3 Scott & White CCOP 1 Montana CCOP 3 South Texas Onc/Hem/San Antonio, U of TX 1 Sutter Hlth Western/Davis, U of CA 3 Thompson Ca Surv Ctr/San Antonio, U of TX 1 Central IL CCOP 2 Tulane University 1 Cleveland Clinic OH 2 Wayne State Univ 1 Grand Rapids CCOP 2 Total (31 Institutions) 103


S0010/II

S0010 Phase II

A Phase II Trial of 506U78 (IND 52611) in Patients with Relapsed or Refractory Non T-Cell Acute Lymphoblastic Leukemia (ALL)

Study Coordinators: S Coutre, D Boldt, M Slovak, D Head




Objectives To test whether the complete remission rate in adult patients with relapsed or refractory non T-cell acute lymphoblastic leukemia (ALL) is sufficiently high following treatment with 506U78 to warrant further investigation.

To estimate the frequency and severity of toxicities associated with the dosing schedule of 506U78 outlined by this protocol.

To investigate in a preliminary manner the frequency and prognostic significance of multidrug resistance gene expression and function (measured prior to treatment), and of cell cycle regulatory gene abnormalities and minimal residual disease detected by RT-PCR or multiparameter flow cytometry (measured during clinical remission), in patients with relapsed or refractory adult non T-cell ALL.

Patient Population Patients must have a prior morphologic diagnosis of acute lymphoblastic leukemia (ALL) with FAB class L1-L2 and be either refractory to a standard induction regimen or have relapsed following successful prior induction therapy. Patients must have evidence of non T-cell ALL in

their blood or marrow, or in at least one extramedullary disease site.

Patients must have passed their 16th birthday and have a Zubrod performance status of 0-3. Patients must have adequate renal and hepatic function, must be negative for CNS involvement of ALL, and must not have neuropathy ≥ Grade 2.

Accrual Goals Initially, 20 eligible patients will be accrued. If fewer than two of these patients achieve CR then the study will be closed. Otherwise, 15 additional eligible patients will be accrued for a total of 35 patients.

Summary Statement As of December 31, 2001, 10 patients have been accrued to this study. Nine of the 10 patients are off treatment: two patients refused further treatment, one died while on treatment of causes not related to protocol treatment, one came off treatment due to neurotoxicity, one was not offered cycle two treatment in error, and the reasons off treatment are pending for the other four patients.

Nine patients have been evaluated for toxicities. One patient died due to infection and no Grade 4 non-hematologic toxicities have been reported.


S0010/II



Arizona, U of 3Stanford University/City of Hope Med Ctr 3New Mexico MBCCOP 2South Texas Onc/Hem/San Antonio, U of TX 1Wichita CCOP 1Total (5 Institutions) 10

Registration, Eligibility, and Evaluability Registrations ending December 31, 2001; Data as of February 7, 2002

506U78 506U78 NUMBER REGISTERED 10 TOXICITY ASSESSMENT 10

ELIG./ PEND. ELIG. 10 Evaluable 9 Analyzable, Pend. Elig. 4 Not Evaluable 1

Patient Characteristics All eligible and selected ineligible patients included

Registrations ending December 31, 2001; Data as of February 7, 2002

506U78 (n=10)

506U78 (n=10)

AGE RACE Median 27 .5 White (Non-Hispanic) 3 30% Minimum 20 Hispanic 4 40% Maximum 70 Asian or Pacific Islander 1 10% American Indian 2 20% SEX Males 6 60% Females 4 40%

Treatment Summary All eligible and selected ineligible patients included

Registrations ending December 31, 2001; Data as of February 7, 2002

506U78 NUMBER ON PROTOCOL TREATMENT 1 NUMBER OFF PROTOCOL TREATMENT 9 REASON OFF TREATMENT Treatment completed as planned 0 Toxicity or side effects 1 Refusal unrelated to toxicity 2 Progression/relapse 0 Death 1 Other - not protocol specified 1 Reason under review 4MAJOR PROTOCOL DEVIATIONS 0


S0020/II

S0020 Phase II

A Phase II Study of Anti-Thymocyte Globulin and Cyclosporine for Patients with Myelodysplastic Syndrome (MDS)

Study Coordinators: C Schiffer, J Anderson, C Willman, M Slovak, D Head

Statisticians: K Kopecky, H Gundacker



Objectives To test whether immunosuppressive therapy with anti-thymocyte globulin (ATG) and cyclosporine is sufficiently effective with respect to response in myelodysplastic syndrome (MDS) to warrant further investigation in Phase III trials.

To estimate the frequency and severity of toxicities associated with this regimen.

To investigate in a preliminary manner the correlation of response to treatment with in vitro assessment of T-lymphocyte subsets.

Patient Population Patients must have a morphologically confirmed diagnosis of MDS in one of the following subclassifications, refractory anemia (RA), refractory anemia with ring sideroblasts (RARS), refractory anemia with excess blasts (RAEB), and must be in the low, intermediate-1, or intermediate-2 IPSS risk category.

Patients must not have undergone bone marrow or stem cell transplant or received prior chemotherapy as treatment for MDS. Prior treatment with cytokines, colony stimulating

factors, erythropoietin, amifostine, or hydroxyurea is permitted. Patients who have received prior chemotherapy and/or radiation therapy for other malignant disorders and in whom the MDS is felt to be secondary to the prior therapy are eligible for this study. Patients must have received transfusions of at least four units of red blood cells as supportive care for anemia during the 60 days before registration.

Patients must have a Zubrod performance status of 0,1 or 2 and must be HIV negative.

Stratification/Descriptive Factors Patients will be stratified by FAB classification: RA vs RARS vs RAEB.

Accrual Goals The accrual goals for this study are 53 eligible patients with RA, 33 eligible patients with RARS, and 44 eligible patients with RAEB for a total of 130 eligible patients.

Summary Statement As of December 31, 2001, four patients have been accrued to this study, two with RARS and two with RAEB.



Ozarks Reg CCOP 2Grand Rapids CCOP 1Wichita CCOP 1Total (3 Institutions) 4


S0106/III

S0106 Phase III

A Phase III Study of Gemtuzumab Ozogamicin (MylotargTM) as Post-Consolidation Therapy for Patients Under Age 56 with Previously Untreated

Acute Myeloid Leukemia (AML)

Study Coordinators: S Petersdorf, D Head, M Slovak, C Willman



Schema

REGISTRATI

ON

Idarubicin+ Ara-C

High DoseAra-C

Observation

GemtuzumabOzogamicin

Induction

RANDOMIZATI

ON

REGISTRATI

ON

CR*MaintainCR

ConsolidationPost-Consolidation

* Patients who do not achieve CR after initial induction may be eligible for asecond induction treatment (see protocol Section 7.2e, f and g). Patients notattaining CR after the second induction, or those not eligible for the secondinduction are removed from protocol treatment.

Objectives To compare disease-free survival (DFS) of patients under age 56 with previously untreated, non-M3, CD33+ AML who receive gemtuzumab ozogamicin or no further treatment after consolidation therapy.

To estimate the frequency and severity of toxicities of the gemtuzumab ozogamicin regimen.

To evaluate the prognostic significance of FLT3 mutations prior to therapy, and of minimal residual disease in remission specimens collected before and after consolidation therapy and after

post-consolidation therapy with gemtuzumab ozogamicin.

Patient Population Patients must have a morphologically confirmed diagnosis of acute myeloid leukemia (AML) with FAB classification other than M3, based on bone marrow aspiration and biopsy performed within 14 days prior to registration. Patients with M3 AML or blastic transformation of chronic myelogenous leukemia are not eligible.

Patients must not have received systemic chemotherapy or more than one dose of intrathecal chemotherapy for acute leukemia.


S0106/III

Administration of hydroxyurea to control high cell counts prior to registration is permitted.

Patients must have reached their 18th birthday but not reached their 56th birthday and must have a Zubrod performance status of 0, 1, 2, or 3. Patients must have normal hepatic and left ventricular function. Patients with unstable cardiac arrhythmias or unstable angina are not eligible.

A pretreatment specimen of marrow and/or blood must be submitted to the Southwest Oncology Group Myeloid Repository because the patients' CD33 status as determined by the Repository must be known in order to determine eligibility for the post-consolidation randomization.

Stratification/Descriptive Factors Patients randomized to the post-consolidation registration are stratified by preinduction cytogenetic risk status: favorable vs intermediate vs unfavorable vs indeterminate.

Accrual Goals The accrual goal for this study is to register 256 eligible CD33+ patients for the post-consol-idation randomization. This is expected to require approximately 568 eligible patients registered for induction therapy. Three interim analyses will be conducted during the course of this study; they are expected to occur at about 36, 56, and 72 months after study activation, depending on the accrual rate.


S0112/II

S0112 Phase II

A Phase II Study of Daunomycin and Ara-C, Both Given by Continuous IV Infusion For Previously Untreated Non-M3 Acute Myeloid Leukemia (AML)

in Patients of Age 56 or Older

Study Coordinators: T Chauncey, A List, D Head, M Slovak, C Willman




Objectives To test whether an induction regimen of daunomycin and Ara-C, both given by continuous intravenous infusion, is sufficiently effective for previously untreated non-M3 AML in patients age 56 or older to warrant investigation in Phase III trials.

To estimate the frequency and severity of toxicities of this regimen in this group of patients.

To assess in a preliminary manner the frequency and prognosis of functional and phenotypic P-glycoprotein (Pgp) expression, cytogenetics, and pharmacokinetic characteristics in this population.

Patient Population Patients must have a morphologically confirmed diagnosis of acute myeloid leukemia (AML) with FAB classification other than M3, based on bone marrow aspiration and biopsy performed within 14 days prior to registration. Patients with M3 AML or blastic transformation of chronic myelogenous leukemia are not eligible.

Patients must not have received prior systemic chemotherapy for acute leukemia. Administration of hydroxyurea to control high cell counts prior to

registration is permitted. A history of prior treatment of MDS with low dose cytosine arabinoside is permitted; however, 30 days must have elapsed from prior treatment and all toxicities resolved. If indicated, a single dose of intrathecal chemotherapy may also be given before or concurrent with induction chemotherapy.

Patients must have reached their 56th birthday. Patients must have a Zubrod performance status of 0-3 and must have adequate hepatic, renal, and cardiac function. Patients with unstable cardiac arrhythmias or unstable angina are not eligible.

Accrual Goals Initially, 30 eligible patients will be accrued. If fewer than nine of these patients achieve CR the study will be closed. Otherwise, 25 additional eligible patients will be accrued for a total of 55 eligible patients.

Summary Statement As of December 31, 2001, eleven patients have been accrued to this study. Four patients have been evaluated for toxicities and no non-hematologic toxicities of Grade 4 or higher have been reported.


S0112/II



Wichita CCOP 3

Puget Sound 2 St Louis CCOP 2 Akron Gen Med Ctr/Cleveland Clinic OH 1 Columbus CCOP 1 Grand Rapids CCOP 1 Upstate Carolina 1 Total (7 Institutions) 11


S0117/II

S0117 Phase II

A Phase II Study of Gemtuzumab Ozogamicin (MylotargTM) and Standard Dose Ara-C for Patients with Relapsed Acute Myeloid Leukemia (AML).

Study Coordinators: J Godwin, M O'Donnell, D Head, M Slovak, C Willman



Objectives To test whether an induction regimen of standard dose Ara-C combined with gemtuzumab ozogamicin (MylotargTM) is sufficiently safe and effective therapy for patients with relapsed acute myeloid leukemia (AML) to warrant further investigation in Phase III trials.


To assess in a preliminary manner the prognostic significance of drug resistance phenotype, cytogenetics, and molecular genetic characteristics in this group of patients.

Patient Population Patients must have a morphologically confirmed diagnosis of acute myeloid leukemia (AML) with FAB classification other than M3, based on bone marrow aspiration and biopsy performed within 14 days prior to registration. Patients with M3 AML or blastic transformation of chronic myelogenous leukemia are not eligible. Patients with prior MDS or secondary AML are eligible. Patients must be in relapse from documented CR.

Patients must not have received prior MylotargTM for acute leukemia. Patients relapsing following autologous or allogeneic hematopoietic stem-cell transplant are not eligible for this trial. Administration of hydroxyurea to control high cell counts prior to registration is permitted. Prior treatment with other investigational agents is permitted; however, four weeks must have elapsed from prior treatment and all toxicities resolved.

Patients must be CD33 positive, be at least 18 years of age, and have a Zubrod performance status of 0, 1, or 2. Patients must have adequate hepatic function, must not have clinical or documented CNS involvement with AML, and must have a WBC ≤ 30,000. Patients with unstable cardiac arrhythmias or unstable angina are not eligible.

Accrual Goals Initally, 30 eligible patients will be accrued. If fewer than nine of these patients acheive CR, the study will be closed. Otherwise, 25 additional eligible patients will be accrued for a total of 55 eligible patients.


S0125/II

S0125 Phase II

A Phase II Study of Chimerism-Mediated Immunotherapy (CMI) Using Nonmyeloablative Allogeneic Transplantation in Older Patients with Acute

Myeloid Leukemia (AML) in First Complete Remission

Study Coordinators: P McSweeney, D Head, M Slovak, C Willman



Objectives To test whether nonmyeloablative allografting using conditioning with pretransplant fludarabine and total body irradiation and post-transplant cyclosporine/mycophenolate mofetil in older patients with AML in first complete remission is sufficiently effective to warrant Phase III investigation.


To perform chimerism studies on blood and marrow cell populations after transplant in order to investigate whether chimerism patterns in bone marrow and blood are associated with relapse and/or GVHD.

To evaluate AML cells at diagnosis for leukemia characteristics that may predict response or relapse with nonmyeloablative allografting.

Patient Population Patients must have a morphologically confirmed diagnosis of AML or secondary AML with FAB classification other than M3, within six months of diagnosis. Patients with M3 AML or blastic transformation of chronic myelogenous leukemia are not eligible. Patients must be in a chemotherapy induced first CR. Patients must have a genotypically HLA-identical sibling who is medically fit and has signed an informed consent to be a donor.

Patients who have received a transplant prior to registration are not eligible.

Patients must be at least 55 but not more than 70 years of age. Patients must have a Zubrod performance status of 0, 1, or 2, must not have active CNS involvement with AML, and must be known to be HIV negative.

Accrual Goals The accrual goal for this study is 51 eligible patients.

Leukemia Committee Agenda - SWOG 2002/Leukemia.pdfDr. Schiffer Proposed Studies S0106 TMA Phase III...

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Transcript of Leukemia Committee Agenda - SWOG 2002/Leukemia.pdfDr. Schiffer Proposed Studies S0106 TMA Phase III...