506U78 in Treating Patients With Refractory Hematologic Cancer

NCT ID: NCT00002970

Last Updated: 2013-07-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 148 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1997-06-30

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.

Detailed Description

OBJECTIVES:

I. 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.

II. 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.

IV. 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.

Conditions

Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Lymphoblastic Lymphoma; T-cell Childhood Acute Lymphoblastic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

nelarabine

Intervention Type: DRUG

Given IV

methotrexate

Intervention Type: DRUG

Given IT

cytarabine

Intervention Type: DRUG

Given IT

therapeutic hydrocortisone

Intervention Type: DRUG

Given IT

Interventions

nelarabine

Given IV

Intervention Type: DRUG

methotrexate

Given IT

Intervention Type: DRUG

cytarabine

Given IT

Intervention Type: DRUG

therapeutic hydrocortisone

Given IT

Intervention Type: DRUG

Other Intervention Names

506U78; Arranon; GW506U78; amethopterin; Folex; methylaminopterin; Mexate; MTX; ARA-C; arabinofuranosylcytosine; arabinosylcytosine; Cytosar-U; cytosine arabinoside; Aeroseb-HC; Barseb HC; Cetacort; Cort-Dome; Cortef

Eligibility Criteria

Inclusion Criteria

• Refractory or recurrent acute lymphocytic leukemia (ALL) or non-Hodgkin's lymphoma (NHL) with bone marrow involvement (T-cell disease only)
• Isolated CNS relapse not eligible
• Performance status - Karnofsky 50-100%
• At least 8 weeks
• Bilirubin no greater than 1.5 mg/dL
• SGPT less than 5 times normal
• Creatinine normal for age
• Creatinine clearance or GFR at least 60 mL/min/1.73m2
• No severe uncontrolled infection
• No concurrent biologic therapy
• Recovered from toxic effects
• At least 6 weeks from administration of nitrosoureas
• No concurrent endocrine therapy
• At least 6 weeks from administration of craniospinal or hemi pelvic radiotherapy

• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Children's Cancer Group

OTHER

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stacey Berg

Role: PRINCIPAL_INVESTIGATOR

Children's Oncology Group

Locations

Children's Oncology Group

Arcadia, California, United States

Countries

United States

Other Identifiers

P9673

Identifier Type: -

Identifier Source: secondary_id

CCG-P9673

Identifier Type: -

Identifier Source: secondary_id

POG-9673

Identifier Type: -

Identifier Source: secondary_id

CDR0000065478

Identifier Type: -

Identifier Source: secondary_id

U10CA098543

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-01836

Identifier Type: -

Identifier Source: org_study_id