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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00005977
First received: July 5, 2000
Last updated: August 19, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Leukemia
Lymphoma
Biological: filgrastim
Drug: cyclophosphamide
Drug: cytarabine
Drug: dexamethasone
Drug: doxorubicin hydrochloride
Drug: etoposide
Drug: ifosfamide
Drug: leucovorin calcium
Drug: methotrexate
Drug: vincristine sulfate
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Event-free survival [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 83
Study Start Date: September 2000
Study Completion Date: September 2006
Primary Completion Date: March 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: STAGE III NHL (Trt 1)

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
Given IV
Other Names:
  • GRANULOCYTE COLONY-STIMULATING FACTOR
  • r-metHuG-CSF
  • G-CSF
  • Neupogen
  • NSC #614629
Drug: cyclophosphamide
Given IV
Other Names:
  • CTX
  • Cytoxan
  • NSC #26271
  • IND #7089
Drug: cytarabine
Given IV
Other Names:
  • cytosine arabinoside
  • Ara-C
  • Cytosar
  • NSC #638
Drug: dexamethasone
Given IV
Other Names:
  • DECADRON
  • NSC #034521
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • Adriamycin
  • NSC #123127
  • IND #7038
Drug: leucovorin calcium
Given IV
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC #3590
Drug: methotrexate
Given IV
Other Names:
  • MTX
  • amethopterin
  • NSC #740
  • IND #4291
Drug: vincristine sulfate
Given IV
Other Names:
  • VCR
  • Oncovin
  • NSC #67574
  • IND #7161
Experimental: STAGE IV NHL, -CNS (Trt 2)

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
Given IV
Other Names:
  • GRANULOCYTE COLONY-STIMULATING FACTOR
  • r-metHuG-CSF
  • G-CSF
  • Neupogen
  • NSC #614629
Drug: cyclophosphamide
Given IV
Other Names:
  • CTX
  • Cytoxan
  • NSC #26271
  • IND #7089
Drug: cytarabine
Given IV
Other Names:
  • cytosine arabinoside
  • Ara-C
  • Cytosar
  • NSC #638
Drug: dexamethasone
Given IV
Other Names:
  • DECADRON
  • NSC #034521
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • Adriamycin
  • NSC #123127
  • IND #7038
Drug: leucovorin calcium
Given IV
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC #3590
Drug: methotrexate
Given IV
Other Names:
  • MTX
  • amethopterin
  • NSC #740
  • IND #4291
Drug: vincristine sulfate
Given IV
Other Names:
  • VCR
  • Oncovin
  • NSC #67574
  • IND #7161
Experimental: STAGE IV, +CNS (Trt 3)

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
Given IV
Other Names:
  • GRANULOCYTE COLONY-STIMULATING FACTOR
  • r-metHuG-CSF
  • G-CSF
  • Neupogen
  • NSC #614629
Drug: cyclophosphamide
Given IV
Other Names:
  • CTX
  • Cytoxan
  • NSC #26271
  • IND #7089
Drug: cytarabine
Given IV
Other Names:
  • cytosine arabinoside
  • Ara-C
  • Cytosar
  • NSC #638
Drug: dexamethasone
Given IV
Other Names:
  • DECADRON
  • NSC #034521
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • Adriamycin
  • NSC #123127
  • IND #7038
Drug: etoposide
Given IV
Other Names:
  • VP-16
  • VePesid
  • NSC #141540
  • IND #9197
Drug: ifosfamide
Given IV
Other Names:
  • IFX
  • IFOS
  • NSC #109724
  • IND #7887
Drug: leucovorin calcium
Given IV
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC #3590
Drug: methotrexate
Given IV
Other Names:
  • MTX
  • amethopterin
  • NSC #740
  • IND #4291
Drug: vincristine sulfate
Given IV
Other Names:
  • VCR
  • Oncovin
  • NSC #67574
  • IND #7161
Experimental: B-ALL, -CNS (Trt 2)

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
Given IV
Other Names:
  • GRANULOCYTE COLONY-STIMULATING FACTOR
  • r-metHuG-CSF
  • G-CSF
  • Neupogen
  • NSC #614629
Drug: cyclophosphamide
Given IV
Other Names:
  • CTX
  • Cytoxan
  • NSC #26271
  • IND #7089
Drug: cytarabine
Given IV
Other Names:
  • cytosine arabinoside
  • Ara-C
  • Cytosar
  • NSC #638
Drug: dexamethasone
Given IV
Other Names:
  • DECADRON
  • NSC #034521
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • Adriamycin
  • NSC #123127
  • IND #7038
Drug: leucovorin calcium
Given IV
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC #3590
Drug: methotrexate
Given IV
Other Names:
  • MTX
  • amethopterin
  • NSC #740
  • IND #4291
Drug: vincristine sulfate
Given IV
Other Names:
  • VCR
  • Oncovin
  • NSC #67574
  • IND #7161
Experimental: B-ALL, +CNS (Trt 3)

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
Given IV
Other Names:
  • GRANULOCYTE COLONY-STIMULATING FACTOR
  • r-metHuG-CSF
  • G-CSF
  • Neupogen
  • NSC #614629
Drug: cyclophosphamide
Given IV
Other Names:
  • CTX
  • Cytoxan
  • NSC #26271
  • IND #7089
Drug: cytarabine
Given IV
Other Names:
  • cytosine arabinoside
  • Ara-C
  • Cytosar
  • NSC #638
Drug: dexamethasone
Given IV
Other Names:
  • DECADRON
  • NSC #034521
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • Adriamycin
  • NSC #123127
  • IND #7038
Drug: etoposide
Given IV
Other Names:
  • VP-16
  • VePesid
  • NSC #141540
  • IND #9197
Drug: ifosfamide
Given IV
Other Names:
  • IFX
  • IFOS
  • NSC #109724
  • IND #7887
Drug: leucovorin calcium
Given IV
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC #3590
Drug: methotrexate
Given IV
Other Names:
  • MTX
  • amethopterin
  • NSC #740
  • IND #4291
Drug: vincristine sulfate
Given IV
Other Names:
  • VCR
  • Oncovin
  • NSC #67574
  • IND #7161

Detailed 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.

  Eligibility

Ages Eligible for Study:   up to 22 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00005977

  Show 119 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Hazem H. Mahmoud, MD Carol G. Simon Cancer Center at Morristown Memorial Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00005977     History of Changes
Other Study ID Numbers: 9917, COG-9917, CDR0000067965
Study First Received: July 5, 2000
Last Updated: August 19, 2013
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
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

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Cytarabine
Methotrexate
Ifosfamide
Isophosphamide mustard
Etoposide phosphate
Dexamethasone
Doxorubicin
Etoposide
Vincristine
Lenograstim
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Leucovorin
Levoleucovorin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 17, 2014