506U78 in Treating Patients With Refractory Hematologic Cancer

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

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.

Study Overview

• Status: Completed
• Conditions: Recurrent Childhood Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Lymphoblastic Lymphoma
• Intervention / Treatment: Drug: cytarabine; Drug: methotrexate; Drug: therapeutic hydrocortisone; Drug: nelarabine

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.

• Study Type: Interventional
• Enrollment (Actual): 148
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Arcadia, California, United States, 91006-3776
      • Children's Oncology Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: cytarabine; Given IT; Other Names: Cytosar-U; cytosine arabinoside; ARA-C; arabinofuranosylcytosine; arabinosylcytosine; Drug: methotrexate; Given IT; Other Names: amethopterin; Folex; methylaminopterin; Mexate; MTX; Drug: therapeutic hydrocortisone; Given IT; Other Names: Aeroseb-HC; Barseb HC; Cetacort; Cort-Dome; Cortef; Drug: nelarabine; Given IV; Other Names: Arranon; 506U78; GW506U78

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Time Frame
Remission duration	Up to 2 years
6 month cumulative event-free survival	6 months

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Collaborators: Children's Cancer Group
• Investigators: Principal Investigator: Stacey Berg, Children's Oncology Group

Study record dates

Study Major Dates

• Study Start: June 1, 1997
• Primary Completion (Actual): January 1, 2005

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: August 8, 2003
• First Posted (Estimate): August 11, 2003

Study Record Updates

• Last Update Posted (Estimate): July 2, 2013
• Last Update Submitted That Met QC Criteria: July 1, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; Leukemia; Recurrence; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Cytarabine; Methotrexate; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate
• Other Study ID Numbers: NCI-2012-01836; U10CA098543 (U.S. NIH Grant/Contract); P9673; CCG-P9673; POG-9673; CDR0000065478