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| Sponsor: | Cancer and Leukemia Group B |
|---|---|
| Collaborator: |
National Cancer Institute (NCI) |
| Information provided by: | Cancer and Leukemia Group B |
| ClinicalTrials.gov Identifier: | NCT00003190 |
Purpose
RATIONALE: Some cancers become resistant to chemotherapy drugs. Combining PSC 833 with more than one chemotherapy drug may reduce resistance to the drugs and allow the cancer cells to be killed. Combining interleukin-2 with combination chemotherapy plus PSC 833 may kill more cancer cells.
PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without PSC 833 followed by interleukin-2 or no further therapy in treating older patients who have acute myeloid leukemia.
| Condition | Intervention | Phase |
|---|---|---|
|
Leukemia |
Biological: Interleukin 2 Drug: cytarabine Drug: daunorubicin hydrochloride Drug: etoposide Drug: PSC-833 |
Phase III |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Phase III Study of MDR Modulation With PSC-833 (NSC #648265) Followed by Immunotherapy With RIL-2 (NSC #373364) VS No Further Therapy In Previously Untreated Patients With AML Greater Than or Equal to 60 Years |
| Enrollment: | 669 |
| Study Start Date: | January 1998 |
| Study Completion Date: | April 2009 |
| Primary Completion Date: | October 2008 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
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Active Comparator: Std Therapy Induction
Patients receive ara-C (cytarabine), daunorubicin, and etoposide for remission induction, followed by a shorter course of the same drugs for consolidation therapy, and then are randomized to either receive immunotherapy with IL-2 or receive no further treatment
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Biological: Interleukin 2
900,000 IU/sq meter/day subQ injection on days 1-14, 19-28, 33-42, 47-56, 61-70, and 75-90 and 12 million IU/sq meter/day subQ injection on days 15-17, 29-31, 43-45, 57-59, and 71-73 to patients randomized to receive IL2.
Drug: cytarabine
100mg/sg meter/day continuous IV infusion on days 1-7 for induction and 100mg/sq meter/day continuous IV infusion on days 1-5 for consolidation
Other Name: Ara-C
Drug: daunorubicin hydrochloride
60mg/sq meter/day bolus injection on days 1, 2, and 3 for induction and 60mg/sq meter/day bolus injection at hrs 2 and 26 for consolidation for Arm 1 and 40mg/sq meter/day bolus injection on days 1,2, and 3 at hours 2, 26, and 50 for induction and 40mg/sq meter/day bolus injection at hrs 2 and 26 for consolidation for Arm 2.
Drug: etoposide
100mg/sq meter/day IV infusion on days 1, 2, and 3 for induction and days 1 and 2 for consolidation for Arm 1 and 60mg/sq meter/day at hrs 2,26,and 50 for induction and hrs 2 and 26 for consolidation for Arm 2
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Experimental: Experimental Induction (CLOSED 8/15/99)
Patients receive std therapy drugs as in Arm 1 with the addition of PSC 833, followed by remission consolidation with the same drugs, then are randomized to either receive IL-2 or no further therapy (CLOSED on 8/15/99)
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Biological: Interleukin 2
900,000 IU/sq meter/day subQ injection on days 1-14, 19-28, 33-42, 47-56, 61-70, and 75-90 and 12 million IU/sq meter/day subQ injection on days 15-17, 29-31, 43-45, 57-59, and 71-73 to patients randomized to receive IL2.
Drug: cytarabine
100mg/sg meter/day continuous IV infusion on days 1-7 for induction and 100mg/sq meter/day continuous IV infusion on days 1-5 for consolidation
Other Name: Ara-C
Drug: daunorubicin hydrochloride
60mg/sq meter/day bolus injection on days 1, 2, and 3 for induction and 60mg/sq meter/day bolus injection at hrs 2 and 26 for consolidation for Arm 1 and 40mg/sq meter/day bolus injection on days 1,2, and 3 at hours 2, 26, and 50 for induction and 40mg/sq meter/day bolus injection at hrs 2 and 26 for consolidation for Arm 2.
Drug: etoposide
100mg/sq meter/day IV infusion on days 1, 2, and 3 for induction and days 1 and 2 for consolidation for Arm 1 and 60mg/sq meter/day at hrs 2,26,and 50 for induction and hrs 2 and 26 for consolidation for Arm 2
Drug: PSC-833
2.8 mg/kg IV infusion over 2 hours at Hr 0 and 10 mg/kg/day by continuous IV infusion hrs 2-74 for induction and 2.8 mg/kg IV infusion over 2 hrs at Hr 0 and 10mg/kg/day continuous IV infusion hours 2-50 for consolidation
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OBJECTIVES: I. Determine whether the addition of PSC 833 to induction chemotherapy improves the complete response rate of patients with acute myeloid leukemia (PSC 833 treatment arm closed as of 8/15/99). II. Determine whether the addition of PSC 833 to induction and consolidation chemotherapy improves survival in this patient population (PSC 833 treatment arm closed as of 8/15/99). III. Determine whether the administration of low-dose and intermittent high- dose interleukin-2 after chemotherapy prolongs disease-free survival in this patient population.
OUTLINE: This is a partially randomized, multicenter study. Patients are stratified according to participating center and disease characteristics (de novo acute myeloid leukemia (AML) versus AML with antecedent myelodysplasia). Patients are randomized to one of two maintenance therapy arms. Arm I: Patients receive cytarabine IV continuously over 7 days and daunorubicin IV bolus followed by etoposide IV over 2 hours on days 1-3. Arm II: (Closed as of 8/15/99) Patients receive treatment as in arm I with the addition of PSC 833 induction. A loading dose of PSC 833 IV is given over 2 hours, followed by a 74-hour continuous infusion of PSC 833 beginning 2 hours before daunorubicin and etoposide. Patients may receive a second induction course if residual leukemia is present in the bone marrow. Patients who experience a complete remission (CR) and meet certain other criteria receive postremission chemotherapy consisting of cytarabine IV continuously over 5 days plus daunorubicin IV followed by etoposide IV over 2 hours on days 1 and 2. Patients who are randomized to receive PSC 833 during induction chemotherapy receive a loading dose of PSC 833 before beginning a 48-hour continuous infusion of PSC 833 concurrently with cytarabine/daunorubicin/etoposide postremission chemotherapy. After completing postremission chemotherapy, patients are randomized to a no further treatment group or interleukin-2 (IL-2) immunotherapy. Treatment begins within 5 months of postremission chemotherapy. IL-2 immunotherapy consists of low-dose subcutaneous (SC) IL-2 on days 1-14, 19-28, 33-42, 47-56, 61-70, and 75-90 and high-dose bolus SC IL-2 on days 15-17, 29-31, 43-45, 57-59, and 71-73. Patients are followed every 2 months for 2 years, every 6 months for 2 years, annually until the tenth year, and then at relapse.
PROJECTED ACCRUAL: Approximately 640 patients will be accrued for this study within 4 years.
Eligibility| Ages Eligible for Study: | 60 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS: Histologically confirmed acute myeloid leukemia (AML), all FAB except M3 (acute promyelocytic leukemia) History of antecedent myelodysplasia allowed No prior treatment for AML or myelodysplasia except: Emergency leukapheresis Emergency treatment for hyperleukocytosis with hydroxyurea Single-dose cranial radiotherapy for CNS leukostasis Growth factor/cytokine support
PATIENT CHARACTERISTICS: Age: 60 and over Performance status: Not specified Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: Not specified Other: Not pregnant or nursing Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics Chemotherapy: See Disease Characteristics No other concurrent chemotherapy Endocrine therapy: No concurrent hormonal therapy except for nondisease-related conditions (e.g., insulin for diabetes or estrogens or progestins for gynecologic conditions) No concurrent steroids (including as antiemetics) except for adrenal failure or septic shock Radiotherapy: See Disease Characteristics No concurrent palliative radiotherapy Surgery: Not specified Other: No concurrent medications that interact with cyclosporine
Contacts and Locations
Show 34 Study Locations| Study Chair: | Maria R. Baer, MD | Roswell Park Cancer Institute |
More Information
| Responsible Party: | Monica M Bertagnolli, MD, Cancer and Leukemia Group B |
| ClinicalTrials.gov Identifier: | NCT00003190 History of Changes |
| Other Study ID Numbers: | CDR0000066022, U10CA031946, CLB-9720 |
| Study First Received: | November 1, 1999 |
| Last Updated: | June 21, 2011 |
| Health Authority: | United States: Food and Drug Administration |
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untreated adult acute myeloid leukemia adult acute erythroid leukemia (M6) adult acute myeloblastic leukemia without maturation (M1) adult acute myeloblastic leukemia with maturation (M2) adult acute myelomonocytic leukemia (M4) |
adult acute monoblastic leukemia (M5a) adult acute megakaryoblastic leukemia (M7) adult acute monocytic leukemia (M5b) adult acute minimally differentiated myeloid leukemia (M0) |
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Leukemia Leukemia, Myeloid, Acute Leukemia, Myeloid Neoplasms by Histologic Type Neoplasms Cytarabine Etoposide phosphate Daunorubicin Etoposide Interleukin-2 Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions |
Antineoplastic Agents Therapeutic Uses Antiviral Agents Anti-Infective Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antibiotics, Antineoplastic Antineoplastic Agents, Phytogenic Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents Central Nervous System Agents |
