Clinical trial NCT00002970: 506U78 in Treating Patients With Refractory Hematologic Cancer
Official title: A Phase II Study of Compound 506U78 in Patients With Refractory T-Cell Malignancies-POG/CCG Intergroup Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Childhood Acute Lymphoblastic Leukemia
Recurrent Childhood Lymphoblastic Lymphoma
T-cell Childhood Acute Lymphoblastic Leukemia
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: Children's Cancer Group
First posted: 2003-08-11
Enrollment: 148
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Early marrow CR plus PR rate at day 21
timeFrame: Day 21
Secondary outcomes:
measure: Remission duration
timeFrame: Up to 2 years
measure: 6 month cumulative event-free survival
timeFrame: 6 months
Other outcomes:
Locations:
city: Arcadia
country: United States
facility: Children's Oncology Group
state: California
Study officials:
affiliation: Children's Oncology Group
name: Stacey Berg
role: PRINCIPAL_INVESTIGATOR
References: