506U78 in Treating Patients With Refractory Hematologic Cancer - Full Text View

Purpose

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	Intervention	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


Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: 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

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Hydrocortisone acetate Hydrocortisone Methotrexate Hydrocortisone sodium succinate Cytarabine Hydrocortisone cypionate Methotrexate sodium Hydrocortisone valerate Hydrocortisone probutate Proctofoam-HC Nelarabine

Genetic and Rare Diseases Information Center resources: Acute Lymphoblastic Leukemia Lymphosarcoma Childhood Acute Lymphoblastic Leukemia Lymphoblastic Lymphoma

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

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%.

Secondary Outcome Measures:

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 ]


Enrollment:	148
Study Start Date:	June 1997
Primary Completion Date:	January 2005 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Arms

Assigned Interventions

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

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


Ages Eligible for Study:	up to 21 Years (Child, Adult)
Genders Eligible for Study:	Both
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002970

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


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
Study First Received:	November 1, 1999
Last Updated:	July 1, 2013
Health Authority:	United States: Food and Drug Administration

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 Cortisol succinate Hydrocortisone acetate 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

ClinicalTrials.gov processed this record on September 26, 2016