Combination Chemotherapy in Treating Patients With Non-Hodgkin's Lymphoma or Acute Lymphocytic Leukemia

Children's Oncology Group

Status and phase: Completed; Phase 3

Conditions: Lymphoma; Leukemia

Treatments: Drug: cyclophosphamide; Drug: methotrexate; Drug: leucovorin calcium; Drug: etoposide; Drug: doxorubicin hydrochloride; Biological: filgrastim; Drug: vincristine sulfate; Drug: cytarabine; Drug: ifosfamide; Drug: dexamethasone

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00005977

CDR0000067965 (Other Identifier)

9917

COG-9917 (Other Identifier)

Details and patient eligibility

About

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 II trial to study the effectiveness of combination chemotherapy in treating patients who have non-Hodgkin's lymphoma or acute lymphocytic leukemia.

Full description

OBJECTIVES:

• Determine if increasing the methotrexate dose in combination with standard treatment is feasible in patients with advanced small noncleaved cell non-Hodgkin's lymphoma or B-cell acute lymphocytic leukemia.
• Assess the toxicity of this intensified therapy in these patients.
• Assess the feasibility of treating these patients that have CNS disease at diagnosis with this intensified therapy plus etoposide and ifosfamide.
• Assess toxicities and late effects of this intensive therapy on the central nervous system, cardiac function, and fertility in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to stage and disease (stage III non-Hodgkin's lymphoma (NHL) vs stage IV NHL with no CNS involvement vs stage IV NHL with CNS involvement vs B-cell acute lymphocytic leukemia (B-ALL) with no CNS involvement vs B-ALL with CNS involvement).

Patients receive methotrexate and cytarabine intrathecally on days 1, 4, 11, and 36 (on day 40 for patients with stage IV NHL or B-ALL only) in combination with alternating courses of: A) cyclophosphamide IV every 12 hours for a total of six doses on days 1-3, doxorubicin IV over 30 minutes on day 4, vincristine IV on days 4 and 11, dexamethasone IV or orally twice daily on days 1-5, and filgrastim (G-CSF) subcutaneously (SQ) or IV over 30 minutes beginning on day 5 and continuing until blood counts recover and B) methotrexate IV over 24 hours on day 18, methotrexate intrathecally on day 18, dexamethasone IV or orally twice daily on days 18-22, leucovorin calcium IV or orally every 6 hours for a total of 6 doses on days 20-21, cytarabine IV over 48 hours on days 20-21, and G-CSF SQ or IV over 30 minutes beginning on day 22 and continuing until blood counts recover. Patients with stage III NHL receive at total of 5 courses of treatment (A-B-A-B-A) and patients with stage IV NHL or B-ALL with no CNS involvement receive a total of 6 courses of treatment (A-B-A-B-A-B).

Patients with CNS involvement receive a third course of treatment: C) etoposide IV over 1 hour on days 36-40, ifosfamide IV over 1 hour on days 36-40, oral dexamethasone twice daily on days 36-40, and G-CSF SQ or IV over 30 minutes beginning on day 41 and continuing until blood counts recover. Patients with CNS involvement receive a total of 7 courses of treatment (A-B-C-A-B-A-B).

Patients are followed every 6 months for 4 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 27-80 patients will be accrued for this study over 24 months.

Enrollment: 83 patients

Sex: All

Ages: Under 22 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• One of the following diagnoses:

  • Histologically confirmed small noncleaved cell non-Hodgkin's lymphoma

    • Stage III or IV
    • Burkitt's or non-Burkitt's by the Working Formulation OR
    • Burkitt's or Burkitt's-like by the REAL classification

  • Histologically confirmed B-cell acute lymphocytic leukemia

    • At least 25% blasts in bone marrow
    • FAB L3 morphology
    • FAB L1 morphology allowed if blasts show B-cell markers (CD19, 20, 22) and surface immunoglobulin positivity
    • Must be registered on POG-9900 in past 8 days

PATIENT CHARACTERISTICS:

Age:

• Under 22 at time of diagnosis

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Other:

• Not pregnant or nursing
• Negative pregnancy test
• HIV positive allowed

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• Not specified

Endocrine therapy:

• No concurrent use of dexamethasone as antiemetic

Radiotherapy:

• Not specified

Surgery:

• Prior surgery allowed

Other:

• No prior therapy except surgery

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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83 participants in 5 patient groups

STAGE III NHL (Trt 1)

Experimental group

Description:

A: Cyclophosphamide (CTX), Doxorubicin hydrochloride, Vincristine sulfate (VCR), Dexamethasone IT Therapy. B: HD-Methotrexate(MTX), Cytarabine(Ara-C), Dexamethasone IT Therapy. Treatment ABABA

Treatment:

Drug: dexamethasone

Drug: vincristine sulfate

Drug: cytarabine

Biological: filgrastim

Drug: doxorubicin hydrochloride

Drug: leucovorin calcium

Drug: methotrexate

Drug: cyclophosphamide

STAGE IV NHL, -CNS (Trt 2)

Experimental group

Description:

A: Cyclophosphamide (CTX), Doxorubicin hydrochloride, Vincristine sulfate (VCR), Dexamethasone IT Therapy. B: HD-Methotrexate(MTX), Cytarabine(Ara-C), Dexamethasone IT Therapy. Treatment ABABAB

Treatment:

Drug: dexamethasone

Drug: vincristine sulfate

Drug: cytarabine

Biological: filgrastim

Drug: doxorubicin hydrochloride

Drug: leucovorin calcium

Drug: methotrexate

Drug: cyclophosphamide

STAGE IV, +CNS (Trt 3)

Experimental group

Description:

A: Cyclophosphamide (CTX), Doxorubicin hydrochloride, Vincristine sulfate (VCR), Dexamethasone IT Therapy. B: HD-Methotrexate(MTX), Cytarabine(Ara-C), Dexamethasone IT Therapy. C: Etoposide, Ifosfamide, Dexamethasone IT Therapy. Treatment ABCABAB

Treatment:

Drug: ifosfamide

Drug: dexamethasone

Drug: vincristine sulfate

Drug: cytarabine

Biological: filgrastim

Drug: doxorubicin hydrochloride

Drug: leucovorin calcium

Drug: etoposide

Drug: methotrexate

Drug: cyclophosphamide

B-ALL, -CNS (Trt 2)

Experimental group

Description:

A: Cyclophosphamide (CTX), Doxorubicin hydrochloride, Vincristine sulfate (VCR), Dexamethasone IT Therapy. B: HD-Methotrexate(MTX), Cytarabine(Ara-C), Dexamethasone IT Therapy. Treatment ABABAB

Treatment:

Drug: dexamethasone

Drug: vincristine sulfate

Drug: cytarabine

Biological: filgrastim

Drug: doxorubicin hydrochloride

Drug: leucovorin calcium

Drug: methotrexate

Drug: cyclophosphamide

B-ALL, +CNS (Trt 3)

Experimental group

Description:

A: Cyclophosphamide (CTX), Doxorubicin hydrochloride, Vincristine sulfate (VCR), Dexamethasone IT Therapy. B: HD-Methotrexate(MTX), Cytarabine(Ara-C), Dexamethasone IT Therapy. C: Etoposide, Ifosfamide, Dexamethasone IT Therapy. Treatment ABCABAB

Treatment:

Drug: ifosfamide

Drug: dexamethasone

Drug: vincristine sulfate

Drug: cytarabine

Biological: filgrastim

Drug: doxorubicin hydrochloride

Drug: leucovorin calcium

Drug: etoposide

Drug: methotrexate

Drug: cyclophosphamide