506U78 in Treating Patients With Refractory Hematologic Cancer

This study has been completed.
Sponsor:
Collaborator:
Children's Cancer Group
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00002970
First received: November 1, 1999
Last updated: July 1, 2013
Last verified: July 2013

November 1, 1999
July 1, 2013
June 1997
January 2005   (final data collection date for primary outcome measure)
Early marrow CR plus PR rate at day 21 [ Time Frame: Day 21 ] [ Designated as safety issue: No ]
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%.
Not Provided
Complete list of historical versions of study NCT00002970 on ClinicalTrials.gov Archive Site
  • Remission duration [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • 6 month cumulative event-free survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
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.

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.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Recurrent Childhood Acute Lymphoblastic Leukemia
  • Recurrent Childhood Lymphoblastic Lymphoma
  • T-cell Childhood Acute Lymphoblastic Leukemia
  • 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
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.

Interventions:
  • Drug: nelarabine
  • Drug: methotrexate
  • Drug: cytarabine
  • Drug: therapeutic hydrocortisone
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
148
Not Provided
January 2005   (final data collection date for primary outcome measure)

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
Both
up to 21 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00002970
NCI-2012-01836, P9673, CCG-P9673, POG-9673, CDR0000065478, U10CA098543
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Children's Cancer Group
Principal Investigator: Stacey Berg Children's Oncology Group
National Cancer Institute (NCI)
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP