506U78 in Treating Patients With Refractory Hematologic Cancer
Study Details
Study Description
Brief Summary
Phase II trial to study the effectiveness of 506U78 in treating patients with recurrent or refractory hematologic cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
OBJECTIVES:
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Determine the response rate to compound 506U78 (2-amino-9-b-D-arabinofuranosyl-6-methoxy-9H-purine) administered as a 1 hour infusion daily for 5 days in patients with recurrent T-cell malignancies.
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Determine the toxicities of compound 506U78 in this group of patients. III. Correlate the biochemical pharmacology of compound 506U78 (e.g., ara-G nucleotides in leukemic blasts and CSF concentrations) with clinical response.
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Determine the impact of compound 506U78 therapy on survival and duration of response of patients with recurrent T-cell malignancies.
OUTLINE: Patients are stratified according to disease characteristics: Group 1: T-cell ALL or NHL in first relapse (greater than 25% bone marrow blasts, with or without concomitant extramedullary relapse other than CNS); Group 2: T-cell ALL or NHL in second or later relapse (greater than 25% bone marrow blasts, with or without concomitant extramedullary relapse other than CNS); Group 3: T-cell ALL or NHL with positive bone marrow and CSF (greater than 5% bone marrow blasts and CNS 2 or 3 involvement); Group 4: Extramedullary relapse and less than 25% blasts in the bone marrow (excluding isolated CNS relapse)
GROUP 1: Patients receive a 1 hour infusion of compound 506U78 daily for 5 days in the absence of neurologic toxicity. The course repeats every 21 days. If a first relapse T-cell ALL study of higher priority is not open, then the patient may continue to receive the drug every 21 days for a maximum of 2 years provided that the patient has achieved a second complete response.
GROUPS 2 and 4: Patients receive compound 506U78 every 21 days for a maximum of 2 years, in the absence of disease progression. After 3 courses a patient may be given CNS prophylaxis with triple intrathecal therapy (TIT), consisting of methotrexate, cytarabine and hydrocortisone after consultation with study coordinator. TIT should be given every 12 weeks.
GROUP 3: Patients receive compound 506U78 every 21 days for a maximum of 2 years, in the absence of disease progression. TIT will be given on day 1 of weeks 1-4, 6, 9 and every 6 weeks for 12 weeks, and then every 9 weeks thereafter. This stratum is open.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm I GROUP 1: Patients receive a 1 hour infusion of compound 506U78 daily for 5 days in the absence of neurologic toxicity. The course repeats every 21 days. If a first relapse T-cell ALL study of higher priority is not open, then the patient may continue to receive the drug every 21 days for a maximum of 2 years provided that the patient has achieved a second complete response. GROUPS 2 and 4: Patients receive compound 506U78 every 21 days for a maximum of 2 years, in the absence of disease progression. After 3 courses a patient may be given CNS prophylaxis with triple intrathecal therapy (TIT), consisting of methotrexate, cytarabine and hydrocortisone after consultation with study coordinator. TIT should be given every 12 weeks. GROUP 3: Patients receive compound 506U78 every 21 days for a maximum of 2 years, in the absence of disease progression. TIT will be given on day 1 of weeks 1-4, 6, 9 and every 6 weeks for 12 weeks, and then every 9 weeks thereafter. This stratum is open. |
Drug: nelarabine
Given IV
Other Names:
Drug: methotrexate
Given IT
Other Names:
Drug: cytarabine
Given IT
Other Names:
Drug: therapeutic hydrocortisone
Given IT
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Early marrow CR plus PR rate at day 21 [Day 21]
CR is defined by an M1 marrow which requires blast counts below 5%. PR is defined by an M2 marrow which requires blast counts below 25%.
Secondary Outcome Measures
- Remission duration [Up to 2 years]
- 6 month cumulative event-free survival [6 months]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Refractory or recurrent acute lymphocytic leukemia (ALL) or non-Hodgkin's lymphoma (NHL) with bone marrow involvement (T-cell disease only)
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Isolated CNS relapse not eligible
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Performance status - Karnofsky 50-100%
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At least 8 weeks
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Bilirubin no greater than 1.5 mg/dL
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SGPT less than 5 times normal
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Creatinine normal for age
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Creatinine clearance or GFR at least 60 mL/min/1.73m2
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No severe uncontrolled infection
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No concurrent biologic therapy
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Recovered from toxic effects
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At least 6 weeks from administration of nitrosoureas
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No concurrent endocrine therapy
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At least 6 weeks from administration of craniospinal or hemi pelvic radiotherapy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Children's Oncology Group | Arcadia | California | United States | 91006-3776 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
- Children's Cancer Group
Investigators
- Principal Investigator: Stacey Berg, Children's Oncology Group
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NCI-2012-01836
- P9673
- CCG-P9673
- POG-9673
- CDR0000065478
- U10CA098543