Combination Chemotherapy in Treating Children With Stage III or Stage IV Non-Hodgkin's Lymphoma or Acute Lymphoblastic Leukemia

Sponsor

Children's Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT00003217

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

102

Duration (Months)

1.4

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.

PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy consisting of methotrexate and cyclophosphamide in treating children who have stage III or stage IV non-Hodgkin's lymphoma or acute lymphoblastic leukemia.

Condition or Disease	Intervention/Treatment	Phase
Leukemia Lymphoma	Biological: filgrastim Drug: cyclophosphamide Drug: cytarabine Drug: dexamethasone Drug: doxorubicin hydrochloride Drug: methotrexate Drug: vincristine sulfate	Phase 1

Detailed Description

OBJECTIVES: I. Evaluate the feasibility and toxicity of dose intensification of methotrexate and cyclophosphamide in patients with stage III or IV small, noncleaved cell non-Hodgkin's lymphoma or B cell acute lymphoblastic leukemia. II. Estimate the response rate and survival of these patients after this therapy.

OUTLINE: This is a two-stage study. Patients will receive cytarabine either by continuous infusion (first stage) or bolus injection (second stage). Patients are stratified by disease (stage III non-Hodgkin's lymphoma (NHL) vs stage IV NHL vs stage B acute lymphoblastic leukemia). Therapy for all patients consists of alternating courses of "A" and "B". Patients with stage III disease receive 4 courses of chemotherapy (ABAB) while those with stage IV disease and B cell acute lymphoblastic leukemia receive 6 chemotherapy courses (ABABAB). Course A - Induction: Patients receive intrathecal methotrexate (IT MTX) and intrathecal cytarabine (IT Ara-C) on days 1, 4, and 11. Dexamethasone is administered by IV or orally twice a day on days 1-5. Cyclophosphamide IV is administered every 12 hours on days 1-3. Doxorubicin IV is administered over 15 minutes beginning 12 hours after the beginning of the 6th dose of cyclophosphamide (day 4). At the same time, vincristine IV is administered, then repeated on day 11. Patients begin filgrastim (granulocyte colony-stimulating factor; G-CSF) subcutaneously or IV over 30 minutes on day 5. Course B - Induction: The first 10 patients enrolled receive cytarabine by continuous infusion while the second 10 patients enrolled receive cytarabine by bolus IV. Patients begin treatment on day 18 and receive methotrexate IV over 24 hours plus IT MTX during hour 1. Dexamethasone is administered by IV or orally twice a day on days 1-5. After completing the 24 hour IV MTX infusion, patients begin cytarabine by continuous infusion over 48 hours or bolus IV every 12 hours for 4 doses. Patients receive G-CSF subcutaneously or IV over 30 minutes beginning on day 22. Patients are assessed for remission status before day 36. Course A - Consolidation: Patients receive dexamethasone IV or orally twice a day on days 1-5. IT MTX and IT Ara-C are administered on days 1 and 4. Cyclophosphamide is administered as during Induction, with vincristine IV and doxorubicin IV over 15 minutes 12 hours later. Vincristine repeats 1 week later. G-CSF administration begins on day 5. Course B - Consolidation: Therapy begins on day 22 with dexamethasone administered as previously. Methotrexate infusion and IT MTX are administered as in Course B - Induction, as is cytarabine (either as a continuous infusion or bolus IV). G-CSF is also administered as previously. Patients are followed monthly for the first 6 months, every 2 months for the next 6 months, then every 6 months for 3 years, then annually thereafter.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study within 16 months.

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Pilot Study of Dose Intensification of Methotrexate and Cyclophosphamide in Patients With Advanced-Stage (III/IV) Small Non-Cleaved Non-Hodgkins Lymphoma and B-Cell All- A Limited Institution Phase III Pilot Study

Study Start Date :

Mar 1, 1998

Actual Primary Completion Date :

Oct 1, 2004

Actual Study Completion Date :

Sep 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment See detailed description.	Biological: filgrastim Other Names: Granulocyte Colony-Stimulating Factor r-metHuG-CSF G-CSF Neupogen NSC #614629 Drug: cyclophosphamide Other Names: CTX Cytoxan NSC #26271 IND #7089 Drug: cytarabine Other Names: cytosine arabinoside Ara-C Cytosar NSC #63878 Drug: dexamethasone Other Names: Decadron NSC #034521 Drug: doxorubicin hydrochloride Other Names: Adriamycin NSC #123127 IND #7038 Drug: methotrexate Other Names: MTX amethopterin NSC #740 IND #4291 Drug: vincristine sulfate Other Names: VCR Oncovin NSC #67574 IND #7161

Arm

Intervention/Treatment

Experimental: Treatment

See detailed description.

Biological: filgrastim

Other Names:

Granulocyte Colony-Stimulating Factor

r-metHuG-CSF

G-CSF

Neupogen

NSC #614629

Drug: cyclophosphamide

Other Names:

CTX

Cytoxan

NSC #26271

IND #7089

Drug: cytarabine

Other Names:

cytosine arabinoside

Ara-C

Cytosar

NSC #63878

Drug: dexamethasone

Other Names:

Decadron

NSC #034521

Drug: doxorubicin hydrochloride

Other Names:

Adriamycin

NSC #123127

IND #7038

Drug: methotrexate

Other Names:

MTX

amethopterin

NSC #740

IND #4291

Drug: vincristine sulfate

Other Names:

VCR

Oncovin

NSC #67574

IND #7161

Outcome Measures

Primary Outcome Measures

Event Free Survival []

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS: Cytologically proven small, noncleaved cell non-Hodgkin's lymphoma, Burkitt's lymphoma, non-Burkitt's lymphoma, or B cell acute lymphoblastic leukemia (B-ALL) Stage III or IV B-ALL - must have FAB L3 morphology and have been registered on POG-9400

PATIENT CHARACTERISTICS: Age: 21 and under Performance status: Not specified Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: Not specified Other: HIV antibody positive allowed Not pregnant or lactating

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior biologic therapy Chemotherapy: No prior chemotherapy Endocrine therapy: Prior emergency steroid therapy may be allowed Radiotherapy: Prior emergency radiotherapy may be allowed Surgery: Prior surgery allowed Other: No concurrent dexamethasone as an anti-emetic

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
2	Lucile Packard Children's Hospital at Stanford	Palo Alto	California	United States	94304
3	Children's Memorial Hospital, Chicago	Chicago	Illinois	United States	60614
4	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
5	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
6	University of Rochester Cancer Center	Rochester	New York	United States	14642
7	State University of New York - Upstate Medical University	Syracuse	New York	United States	13210
8	Oklahoma Memorial Hospital	Oklahoma City	Oklahoma	United States	73126-0307
9	Medical University of South Carolina	Charleston	South Carolina	United States	29425-0721
10	Simmons Cancer Center - Dallas	Dallas	Texas	United States	75235-9154
11	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas	United States	76104
12	Midwest Children's Cancer Center	Milwaukee	Wisconsin	United States	53226
13	Alberta Children's Hospital	Calgary	Alberta	Canada	T2T 5C7
14	Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8