506U78 in Treating Patients With Refractory Hematologic Cancer

Study Description

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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
Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Lymphoblastic Lymphoma; T-cell Childhood Acute Lymphoblastic Leukemia	Drug: nelarabine; Drug: methotrexate; Drug: cytarabine; Drug: therapeutic hydrocortisone	Phase 2

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	148 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase II Study of Compound 506U78 in Patients With Refractory T-Cell Malignancies-POG/CCG Intergroup Study
Study Start Date :	June 1997
Actual Primary Completion Date :	January 2005

Arms and Interventions

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

Outcome Measures

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Primary Outcome Measures :

1. Early marrow CR plus PR rate at day 21 [ Time Frame: 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 :

1. Remission duration [ Time Frame: Up to 2 years ]
2. 6 month cumulative event-free survival [ Time Frame: 6 months ]

Eligibility Criteria

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Ages Eligible for Study:	up to 21 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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Locations

United States, California
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

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00002970 History of Changes
Other Study ID Numbers:	NCI-2012-01836; P9673; CCG-P9673; POG-9673; CDR0000065478; U10CA098543 ( U.S. NIH Grant/Contract )
First Posted:	August 11, 2003
Last Update Posted:	July 2, 2013
Last Verified:	July 2013

Additional relevant MeSH terms:

Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Methotrexate; Cytarabine; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Cortisol succinate; Hydrocortisone

Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Reproductive Control Agents; Physiological Effects of Drugs; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Dermatologic Agents; Enzyme Inhibitors; Folic Acid Antagonists; Immunosuppressive Agents; Immunologic Factors; Antirheumatic Agents; Nucleic Acid Synthesis Inhibitors