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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Leukemia, Lymphoma

Intervention / Treatment
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* Biological: filgrastim
* Drug: cyclophosphamide
* Drug: cytarabine
* Drug: dexamethasone
* Drug: doxorubicin hydrochloride
* Drug: etoposide
* Drug: ifosfamide
* Drug: leucovorin calcium
* Drug: methotrexate
* Drug: vincristine sulfate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 22 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: STAGE III NHL (Trt 1)<br>A: Cyclophosphamide (CTX), Doxorubicin hydrochloride, Vincristine sulfate (VCR), Dexamethasone IT Therapy. B: HD-Methotrexate(MTX), Cytarabine(Ara-C), Dexamethasone IT Therapy. Treatment ABABA | Biological: filgrastim<br>* Given IV<br>* Other names: NSC #614629;Drug: cyclophosphamide<br>* Given IV<br>* Other names: IND #7089;Drug: cytarabine<br>* Given IV<br>* Other names: NSC #638;Drug: dexamethasone<br>* Given IV<br>* Other names: NSC #034521;Drug: doxorubicin hydrochloride<br>* Given IV<br>* Other names: IND #7038;Drug: leucovorin calcium<br>* Given IV<br>* Other names: NSC #3590;Drug: methotrexate<br>* Given IV<br>* Other names: IND #4291;Drug: vincristine sulfate<br>* Given IV<br>* Other names: IND #7161;|
| Experimental: STAGE IV NHL, -CNS (Trt 2)<br>A: Cyclophosphamide (CTX), Doxorubicin hydrochloride, Vincristine sulfate (VCR), Dexamethasone IT Therapy. B: HD-Methotrexate(MTX), Cytarabine(Ara-C), Dexamethasone IT Therapy. Treatment ABABAB | Biological: filgrastim<br>* Given IV<br>* Other names: NSC #614629;Drug: cyclophosphamide<br>* Given IV<br>* Other names: IND #7089;Drug: cytarabine<br>* Given IV<br>* Other names: NSC #638;Drug: dexamethasone<br>* Given IV<br>* Other names: NSC #034521;Drug: doxorubicin hydrochloride<br>* Given IV<br>* Other names: IND #7038;Drug: leucovorin calcium<br>* Given IV<br>* Other names: NSC #3590;Drug: methotrexate<br>* Given IV<br>* Other names: IND #4291;Drug: vincristine sulfate<br>* Given IV<br>* Other names: IND #7161;|
| Experimental: STAGE IV, +CNS (Trt 3)<br>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 | Biological: filgrastim<br>* Given IV<br>* Other names: NSC #614629;Drug: cyclophosphamide<br>* Given IV<br>* Other names: IND #7089;Drug: cytarabine<br>* Given IV<br>* Other names: NSC #638;Drug: dexamethasone<br>* Given IV<br>* Other names: NSC #034521;Drug: doxorubicin hydrochloride<br>* Given IV<br>* Other names: IND #7038;Drug: etoposide<br>* Given IV<br>* Other names: IND #9197;Drug: ifosfamide<br>* Given IV<br>* Other names: IND #7887;Drug: leucovorin calcium<br>* Given IV<br>* Other names: NSC #3590;Drug: methotrexate<br>* Given IV<br>* Other names: IND #4291;Drug: vincristine sulfate<br>* Given IV<br>* Other names: IND #7161;|
| Experimental: B-ALL, -CNS (Trt 2)<br>A: Cyclophosphamide (CTX), Doxorubicin hydrochloride, Vincristine sulfate (VCR), Dexamethasone IT Therapy. B: HD-Methotrexate(MTX), Cytarabine(Ara-C), Dexamethasone IT Therapy. Treatment ABABAB | Biological: filgrastim<br>* Given IV<br>* Other names: NSC #614629;Drug: cyclophosphamide<br>* Given IV<br>* Other names: IND #7089;Drug: cytarabine<br>* Given IV<br>* Other names: NSC #638;Drug: dexamethasone<br>* Given IV<br>* Other names: NSC #034521;Drug: doxorubicin hydrochloride<br>* Given IV<br>* Other names: IND #7038;Drug: leucovorin calcium<br>* Given IV<br>* Other names: NSC #3590;Drug: methotrexate<br>* Given IV<br>* Other names: IND #4291;Drug: vincristine sulfate<br>* Given IV<br>* Other names: IND #7161;|
| Experimental: B-ALL, +CNS (Trt 3)<br>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 | Biological: filgrastim<br>* Given IV<br>* Other names: NSC #614629;Drug: cyclophosphamide<br>* Given IV<br>* Other names: IND #7089;Drug: cytarabine<br>* Given IV<br>* Other names: NSC #638;Drug: dexamethasone<br>* Given IV<br>* Other names: NSC #034521;Drug: doxorubicin hydrochloride<br>* Given IV<br>* Other names: IND #7038;Drug: etoposide<br>* Given IV<br>* Other names: IND #9197;Drug: ifosfamide<br>* Given IV<br>* Other names: IND #7887;Drug: leucovorin calcium<br>* Given IV<br>* Other names: NSC #3590;Drug: methotrexate<br>* Given IV<br>* Other names: IND #4291;Drug: vincristine sulfate<br>* Given IV<br>* Other names: IND #7161;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-free survival | Assess the effect of high dose methotrexate in combination with standard treatment per the POG 9317 protocol on 1-year event-free survival (EFS), monitor and assess toxicity, and estimate the hospitalization costs for the treatment of toxicity related side effects. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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childhood Burkitt lymphoma, L3 childhood acute lymphoblastic leukemia, B-cell childhood acute lymphoblastic leukemia, L3 adult acute lymphoblastic leukemia, B-cell adult acute lymphoblastic leukemia, stage III adult Burkitt lymphoma, stage IV adult Burkitt lymphoma, stage III childhood small noncleaved cell lymphoma, stage IV childhood small noncleaved cell lymphoma