506U78 in Treating Patients With Refractory Hematologic Cancer

Condition(s) targeted: Leukemia; Lymphoma

Intervention: cytarabine (Drug); methotrexate (Drug); nelarabine (Drug); therapeutic hydrocortisone (Drug); chemotherapy (Procedure)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: Pediatric Oncology Group

Official(s) and/or principal investigator(s):
Stacey L. Berg, MD, Study Chair, Affiliation: Texas Children's Cancer Center
Gregory H. Reaman, MD, Study Chair, Affiliation: Children's National Medical Center

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of 506U78 in treating patients with recurrent or refractory hematologic cancer.

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

Study design: Interventional, Treatment

Detailed description: OBJECTIVES:

* 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.

* Determine the toxicities of compound 506U78 in this group of patients.

* Correlate the biochemical pharmacology of compound 506U78 (e. g., ara-G nucleotides in leukemic blasts and CSF concentrations) with clinical response.

* 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.

PROJECTED ACCRUAL: A maximum of 148 patients (37 patients per stratum) will be accrued for this study.

Maximum age: 21 Years. Gender(s): Both.

Criteria:

DISEASE CHARACTERISTICS:

* 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

PATIENT CHARACTERISTICS:

Age:

* 21 and under

Performance status:

* Karnofsky 50-100%

Life expectancy:

* At least 8 weeks

Hematopoietic:

* Not specified

Hepatic:

* Bilirubin no greater than 1. 5 mg/dL

* SGPT less than 5 times normal

Renal:

* Creatinine normal for age

* Creatinine clearance or GFR at least 60 mL/min/1. 73m2

Other:

* No severe uncontrolled infection

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* No concurrent biologic therapy

Chemotherapy:

* Recovered from toxic effects

* At least 6 weeks from administration of nitrosoureas

Endocrine therapy:

* No concurrent endocrine therapy

Radiotherapy:

* At least 6 weeks from administration of craniospinal or hemipelvic radiotherapy

Surgery:

* Not specified

MBCCOP - Gulf Coast, Mobile, Alabama 36688, United States

University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, Alabama 35294-3300, United States

Cross Cancer Institute, Edmonton, Alberta T6G 1Z2, Canada

University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, United States

Lucile Packard Children's Hospital at Stanford, Palo Alto, California 94304, United States

University of California Davis Medical Center, Sacramento, California 95817, United States

University of California San Diego Cancer Center, La Jolla, California 92093-0658, United States

Yale Comprehensive Cancer Center, New Haven, Connecticut 06520-8028, United States

Walter Reed Army Medical Center, Washington, District of Columbia 20307-5000, United States

CCOP - Florida Pediatric, Tampa, Florida 33682-7757, United States

Miami Children's Hospital, Miami, Florida 33155, United States

Shands Hospital and Clinics, University of Florida, Gainesville, Florida 32610-100277, United States

Sylvester Cancer Center, University of Miami, Miami, Florida 33136, United States

Emory University Hospital - Atlanta, Atlanta, Georgia 30322, United States

Swiss Pediatric Oncology Group Bern, Bern CH 3010, Switzerland

Cancer Research Center of Hawaii, Honolulu, Hawaii 96813, United States

Children's Memorial Hospital, Chicago, Chicago, Illinois 60614, United States

CCOP - Wichita, Wichita, Kansas 67214-3882, United States

University of Kansas Medical Center, Kansas City, Kansas 66160-7357, United States

CCOP - Ochsner, New Orleans, Louisiana 70121, United States

MBCCOP - LSU Health Sciences Center, New Orleans, Louisiana 70112, United States

Ochsner Clinic, New Orleans, Louisiana 70121, United States

Marlene & Stewart Greenebaum Cancer Center, University of Maryland, Baltimore, Maryland 21201, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231-2410, United States

Boston Floating Hospital Infants and Children, Boston, Massachusetts 02111, United States

Dana-Farber Cancer Institute, Boston, Massachusetts 02115, United States

University of Massachusetts Memorial Medical Center, Worcester, Massachusetts 01655, United States

Children's Hospital of Michigan, Detroit, Michigan 48201, United States

University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, United States

Cardinal Glennon Children's Hospital, Saint Louis, Missouri 63104, United States

Washington University School of Medicine, Saint Louis, Missouri 63110, United States

CCOP - Northern New Jersey, Hackensack, New Jersey 07601, United States

Hackensack University Medical Center, Hackensack, New Jersey 07601, United States

Saint Peter's University Hospital, New Brunswick, New Jersey 08901-1780, United States

Tomorrows Children's Institute, Hackensack, New Jersey 07601, United States

Mount Sinai School of Medicine, New York, New York 10029, United States

Roswell Park Cancer Institute, Buffalo, New York 14263-0001, United States

Schneider Children's Hospital, New Hyde Park, New York 11042, United States

State University of New York - Upstate Medical University, Syracuse, New York 13210, United States

University of Rochester Cancer Center, Rochester, New York 14642, United States

Carolinas Medical Center, Charlotte, North Carolina 28232-2861, United States

Comprehensive Cancer Center at Wake Forest University, Winston-Salem, North Carolina 27157-1082, United States

Duke Comprehensive Cancer Center, Durham, North Carolina 27710, United States

East Carolina University School of Medicine, Greenville, North Carolina 27858-4354, United States

Mission Saint Joseph's Health System, Asheville, North Carolina 28801, United States

Presbyterian Healthcare, Charlotte, North Carolina 28233-3549, United States

Oklahoma Memorial Hospital, Oklahoma City, Oklahoma 73126-0307, United States

Children's Hospital, Hamilton, Ontario L8N 3Z5, Canada

Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada

CCOP - Columbia River Program, Portland, Oregon 97213, United States

St. Christopher's Hospital for Children, Philadelphia, Pennsylvania 19134-1095, United States

Hopital Sainte Justine, Montreal, Quebec H3T 1C5, Canada

McGill University Health Center - Montreal Children's Hospital, Montreal, Quebec H3H 1P3, Canada

Children's Hospital of Greenville Hospital System, Greenville, South Carolina 29605, United States

Medical University of South Carolina, Charleston, South Carolina 29425-0721, United States

Saint Jude Children's Research Hospital, Memphis, Tennessee 38105-2794, United States

Baylor College of Medicine, Houston, Texas 77030, United States

MBCCOP - South Texas Pediatric, San Antonio, Texas 78229-3900, United States

Simmons Cancer Center - Dallas, Dallas, Texas 75235-9154, United States

Texas Children's Cancer Center, Houston, Texas 77030-2399, United States

University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284-7811, United States

Cancer Center at the University of Virginia, Charlottesville, Virginia 22908, United States

Massey Cancer Center, Richmond, Virginia 23298-0037, United States

Naval Medical Center, Portsmouth, Portsmouth, Virginia 23708-2197, United States

Midwest Children's Cancer Center, Milwaukee, Wisconsin 53226, United States

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: August 1998
Last updated: March 5, 2007