506U78 in Treating Patients With Refractory Hematologic Cancer

Recurrent Childhood Acute Lymphoblastic Leukemia Clinical Trial

Official title:

A Phase II Study of Compound 506U78 in Patients With Refractory T-Cell Malignancies-POG/CCG Intergroup Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002970
• Other study ID #: NCI-2012-01836
• Secondary ID: P9673CCG-P9673PO
• Status: Completed
• Phase: Phase 2
• First received: November 1, 1999
• Last updated: July 1, 2013
• Start date: June 1997

Study information

• Verified date: July 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 148
• Est. primary completion date: January 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 21 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Recurrent Childhood Acute Lymphoblastic Leukemia
• Recurrent Childhood Lymphoblastic Lymphoma
• T-cell Childhood Acute Lymphoblastic Leukemia

Intervention

Drug:
• nelarabine
Given IV
• methotrexate
Given IT
• cytarabine
Given IT
• therapeutic hydrocortisone
Given IT

Locations

Country	Name	City	State
United States	Children's Oncology Group	Arcadia	California

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	Children's Cancer Group

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Early marrow CR plus PR rate at 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%.	Day 21	No
Secondary	Remission duration		Up to 2 years	No
Secondary	6 month cumulative event-free survival		6 months	No