Combination Chemotherapy in Treating Patients With Acute Lymphoblastic Leukemia or Advanced Lymphoblastic Non-Hodgkin's Lymphoma (T-Cell #4)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT01230983
First received: October 28, 2010
Last updated: June 4, 2013
Last verified: June 2013
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Dexrazoxane may lessen the side effects of chemotherapy.

PURPOSE: Randomized phase III trial to compare combination chemotherapy with or without dexrazoxane and with or without high-dose methotrexate in patients with acute lymphoblastic leukemia or advanced lymphoblastic non-Hodgkin's lymphoma.


Condition Intervention Phase
Cardiac Toxicity
Leukemia
Lymphoma
Drug: asparaginase
Drug: cytarabine
Drug: dexrazoxane hydrochloride
Drug: doxorubicin hydrochloride
Drug: leucovorin calcium
Drug: mercaptopurine
Drug: methotrexate
Drug: prednisone
Drug: therapeutic hydrocortisone
Drug: vincristine sulfate
Radiation: radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Supportive Care
Official Title: Intensive Treatment For T-CELL Acute Lymphoblastic Leukemia and Advanced Stage Lymphoblastic Non-Hodgkin's Lymphoma: A Pediatric Oncology Group Phase III Study

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Complete Continuous Remission [ Time Frame: Time to failure for any cause among patients achieving a complete response ] [ Designated as safety issue: No ]
    Since all patients receive the same induction, the endpoint will be CCR , i.e. complete continuous remission (the time to failure for any cause among patients achieving a complete response)


Secondary Outcome Measures:
  • Abnormalities in the 31 week and the year 3 echocardiograms [ Time Frame: 1 year off therapy ] [ Designated as safety issue: No ]
    Endpoint will be abnormalities in the 31 week and the year 3 echocardiograms (i.e. year 1 off therapy). Secondarily, we shall compare the CCR rates for the two treatment regimens, in a two sided fashion.


Enrollment: 573
Study Start Date: June 1996
Study Completion Date: October 2004
Primary Completion Date: September 2001 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment 1: (No HD MTX / No Zinecard)
Closed 09/2000 Induction (Vincristine sulfate, Prednisone, doxorubicin hydrochloride, Methotrexate (MTX), mercaptopurine (6-MP), methotrexate/cytarabine), Consolidation (Vincristine sulfate), Prednisone, doxorubicin hydrochloride, mercaptopurine (6-MP), asparaginase, IT methotrexate /cytarabine radiation therapy (XRT)). Continuation (Vincristine sulfate, Prednisone, IT methotrexate/Ara-C,mercaptopurine (6-MP), IT methotrexate/cytarabine)
Drug: asparaginase
Given IV
Other Names:
  • E. coli
  • Elspar
  • NSC #10922
Drug: cytarabine
Given IV
Other Names:
  • Cytosine Arabinoside
  • AraC
  • Cytosar
  • NSC #06387
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • Doxorubicin
  • NSC #123127
Drug: mercaptopurine
Given orally
Other Names:
  • 6-MP
  • Purinethol
  • NSC #000755
Drug: methotrexate
Given IV
Other Names:
  • MTX
  • amethopterin
  • NSC #000740
Drug: prednisone
Given orally
Other Names:
  • Deltasone
  • Meticorten
  • Liquid Pred
  • NSC #010023
Drug: therapeutic hydrocortisone
Given IT
Other Names:
  • hydrocortisone sodium succinate
  • Solu-cortef
  • NSC #010483
Drug: vincristine sulfate
Given IV
Other Names:
  • VCR
  • Oncovin
  • NSC #067574
Radiation: radiation therapy
Radiation to cranium
Other Name: XRT
Active Comparator: Treatment 2: (No HD MTX / Zinecard)
Closed 09/2000 Induction (Vincristine sulfate, Prednisone, doxorubicin hydrochloride, Methotrexate (MTX), mercaptopurine (6-MP), methotrexate/cytarabine, dexrazoxane hydrochloride (Zinecard or DZR)), Consolidation (Vincristine sulfate), Prednisone, doxorubicin hydrochloride, mercaptopurine (6-MP), asparaginase, dexrazoxane hydrochloride (Zinecard or DZR), IT methotrexate /cytarabine, radiation therapy (XRT)). Continuation (Vincristine sulfate, Prednisone, IT methotrexate/Ara-C,mercaptopurine (6-MP), IT methotrexate/cytarabine)
Drug: asparaginase
Given IV
Other Names:
  • E. coli
  • Elspar
  • NSC #10922
Drug: cytarabine
Given IV
Other Names:
  • Cytosine Arabinoside
  • AraC
  • Cytosar
  • NSC #06387
Drug: dexrazoxane hydrochloride
Given IV
Other Names:
  • DZR
  • ADR-529
  • ZINECARD
  • ICRF-187
  • NSC #169780
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • Doxorubicin
  • NSC #123127
Drug: mercaptopurine
Given orally
Other Names:
  • 6-MP
  • Purinethol
  • NSC #000755
Drug: methotrexate
Given IV
Other Names:
  • MTX
  • amethopterin
  • NSC #000740
Drug: prednisone
Given orally
Other Names:
  • Deltasone
  • Meticorten
  • Liquid Pred
  • NSC #010023
Drug: therapeutic hydrocortisone
Given IT
Other Names:
  • hydrocortisone sodium succinate
  • Solu-cortef
  • NSC #010483
Drug: vincristine sulfate
Given IV
Other Names:
  • VCR
  • Oncovin
  • NSC #067574
Radiation: radiation therapy
Radiation to cranium
Other Name: XRT
Active Comparator: Treatment 3: (HD MTX / No Zinecard)
Closed 09/2001 Induction (Vincristine sulfate, Prednisone, doxorubicin hydrochloride, Methotrexate (MTX), mercaptopurine (6-MP), leucovorin calcium (LCV), HD methotrexate/cytarabine), Consolidation (Vincristine sulfate), Prednisone, doxorubicin hydrochloride, mercaptopurine (6-MP), asparaginase, leucovorin calcium (LCV), HD methotrexate /cytarabine radiation therapy (XRT)). Continuation (Vincristine sulfate, Prednisone, IT methotrexate/Ara-C,mercaptopurine (6-MP), HD methotrexate/cytarabine)
Drug: asparaginase
Given IV
Other Names:
  • E. coli
  • Elspar
  • NSC #10922
Drug: cytarabine
Given IV
Other Names:
  • Cytosine Arabinoside
  • AraC
  • Cytosar
  • NSC #06387
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • Doxorubicin
  • NSC #123127
Drug: leucovorin calcium
Given IV
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC #003590
Drug: mercaptopurine
Given orally
Other Names:
  • 6-MP
  • Purinethol
  • NSC #000755
Drug: methotrexate
Given IV
Other Names:
  • MTX
  • amethopterin
  • NSC #000740
Drug: prednisone
Given orally
Other Names:
  • Deltasone
  • Meticorten
  • Liquid Pred
  • NSC #010023
Drug: therapeutic hydrocortisone
Given IT
Other Names:
  • hydrocortisone sodium succinate
  • Solu-cortef
  • NSC #010483
Drug: vincristine sulfate
Given IV
Other Names:
  • VCR
  • Oncovin
  • NSC #067574
Radiation: radiation therapy
Radiation to cranium
Other Name: XRT
Active Comparator: Treatment 4: (HD MTX / Zinecard)
Closed 09/2001 Induction (Vincristine sulfate, Prednisone, doxorubicin hydrochloride, Methotrexate (MTX), mercaptopurine (6-MP), leucovorin calcium (LCV), HD methotrexate/cytarabine, dexrazoxane hydrochloride (Zinecard or DZR)), Consolidation (Vincristine sulfate), Prednisone, doxorubicin hydrochloride, mercaptopurine (6-MP), asparaginase, HD methotrexate /cytarabine, dexrazoxane hydrochloride (Zinecard or DZR), radiation therapy (XRT)). Continuation (Vincristine sulfate, Prednisone, IT methotrexate/Ara-C,mercaptopurine (6-MP), HD methotrexate/cytarabine)
Drug: asparaginase
Given IV
Other Names:
  • E. coli
  • Elspar
  • NSC #10922
Drug: cytarabine
Given IV
Other Names:
  • Cytosine Arabinoside
  • AraC
  • Cytosar
  • NSC #06387
Drug: dexrazoxane hydrochloride
Given IV
Other Names:
  • DZR
  • ADR-529
  • ZINECARD
  • ICRF-187
  • NSC #169780
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • Doxorubicin
  • NSC #123127
Drug: leucovorin calcium
Given IV
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC #003590
Drug: mercaptopurine
Given orally
Other Names:
  • 6-MP
  • Purinethol
  • NSC #000755
Drug: methotrexate
Given IV
Other Names:
  • MTX
  • amethopterin
  • NSC #000740
Drug: prednisone
Given orally
Other Names:
  • Deltasone
  • Meticorten
  • Liquid Pred
  • NSC #010023
Drug: therapeutic hydrocortisone
Given IT
Other Names:
  • hydrocortisone sodium succinate
  • Solu-cortef
  • NSC #010483
Drug: vincristine sulfate
Given IV
Other Names:
  • VCR
  • Oncovin
  • NSC #067574
Radiation: radiation therapy
Radiation to cranium
Other Name: XRT

Detailed Description:

OBJECTIVES: I. Determine, in a randomized trial, the effectiveness of high-dose methotrexate when added to a multiagent chemotherapy backbone (the Dana Farber Cancer Institute regimen, protocol DFCI-87001) proven effective in T-cell acute lymphoblastic leukemia (T-ALL) and advanced lymphoblastic non-Hodgkin's lymphoma (NHL). II. Determine the role of dexrazoxane in preventing cardiotoxicity in children with T-ALL and advanced lymphoblastic NHL treated with an anthracycline-based regimen. III. Study the biology of T-cell lymphoid malignancies by accumulating data on the concurrent ALL classification study (POG-9400) and analyzing the data relative to outcome. IV. Evaluate the correlation of minimal residual disease (using the TAL 1 proto-oncogene) with event-free survival. V. Determine the role of p53 and p16 tumor suppressor genes in T-ALL. VI. Determine whether drug sensitivity profiles of blast cells to doxorubicin, methotrexate, and cytarabine correlate with initial response and subsequent relapse.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to disease category (acute lymphoblastic leukemia (ALL) with no CNS disease vs. ALL with CNS disease vs. non-Hodgkin's lymphoma (NHL) with no CNS disease vs. NHL with CNS disease), gender, race (Caucasian vs. African American vs. Hispanic). Patients are randomized to one of four treatment arms. ARM I: During induction therapy, patients receive vincristine IV once daily on days 1, 8, 15, and 22, oral prednisone three times a day on days 1-21, doxorubicin IV daily on days 1, 2, and 22, methotrexate IV once, at least 8 hours after doxorubicin on day 2, and oral mercaptopurine daily on days 22-35. Patients receive triple intrathecal therapy (TIT) consisting of methotrexate, cytarabine, and hydrocortisone on weeks 1, 3, 4, 5, and 6. Patients with CNS 2 or 3 disease receive TIT on week 2. During weeks 7-33, patients receive consolidation therapy consisting of vincristine IV once every 3 weeks, oral prednisone three times a day over 5 days, every 3 weeks, doxorubicin IV once every 3 weeks, oral mercaptopurine daily for 14 days, every 3 weeks, and asparaginase intramuscularly (IM) weekly on weeks 7-26. Patients receive TIT on week 10 and 22 (on week 16 for patients with CNS 2 or 3 disease). Patients receive radiotherapy beginning on week 22. During weeks 34-108, patients receive continuation therapy consisting of vincristine IV once every 3 weeks, oral prednisone three times a day over 5 days, every 3 weeks, methotrexate IV or IM weekly (omitted during TIT) and oral mercaptopurine daily for 14 days, every 3 weeks. Patients receive TIT on weeks 40, 58, 76, and 94. Arm II: Patients receive induction therapy as in Arm I with an addition of dexrazoxane IV given prior to doxorubicin on days 1, 2, and 22. Patients receive consolidation therapy as in Arm I with an addition of dexrazoxane IV given prior to doxorubicin once every 3 weeks. Patients receive continuation therapy as in Arm I. Arm III: Patients receive induction therapy as in Arm I in addition to high dose methotrexate IV on week 4 and leucovorin calcium IV or orally every 6 hours for 7 doses beginning 36 hours after high dose methotrexate. Patients receive consolidation therapy as in Arm I in addition to high dose methotrexate IV on weeks 7, 10, and 13 followed by leucovorin calcium as in induction therapy. Patients receive continuation therapy as in Arm I. Arm IV: Patients receive induction therapy and consolidation therapy as in Arms I, II, and III. Patients receive continuation therapy as in Arm I. Treatment continues for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months for 1 year, every 4 months for 3 years, then every 6 months for 2 years.

PROJECTED ACCRUAL: A total of 494 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS: T-cell acute lymphoblastic leukemia (ALL) Registration on current ALL classification study (POG-9400) required within 6 working days prior to entry DR-, T+ DR-, T- or DR+, T+ eligible if T-cell ALL confirmed at the Johns Hopkins Reference Laboratory Biopsy-proven diffuse lymphoblastic lymphoma Murphy stage III/IV disease Registered on ALL classification study (POG-9400)

PATIENT CHARACTERISTICS: Age: Over 12 months to under 22 years for T-ALL Under 22 years for lymphoma

PRIOR CONCURRENT THERAPY: No prior therapy other than steroids or emergency mediastinal irradiation in patients with severe respiratory distress from mediastinal disease Steroid treatment allowed provided that physical examination and complete blood count with differential were performed immediately prior to beginning steroids and results of both are known

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01230983

Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Barbara L. Asselin, MD James P. Wilmot Cancer Center
  More Information

Additional Information:
Publications:
Matloub Y, Asselin BL, Stork LC, et al.: Outcome of children with T-Cell acute lymphoblastic leukemia (T-ALL) and standard risk (SR) features: results of CCG-1952, CCG-1991 and POG 9404. [Abstract] Blood 104 (11): A-680, 195a, 2004.
Seibel NL, Asselin BL, Nachman JB, et al.: Treatment of high risk T-cell acute lymphoblastic leukemia (T-ALL): comparison of recent experience of the Children's Cancer Group (CCG) and Pediatric Oncology Group (POG). [Abstract] Blood 104 (11): A-681, 2004.

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT01230983     History of Changes
Other Study ID Numbers: 9404, U10CA030969, POG-9404, CDR0000064664
Study First Received: October 28, 2010
Last Updated: June 4, 2013
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
stage III childhood lymphoblastic lymphoma
stage IV childhood lymphoblastic lymphoma
untreated childhood acute lymphoblastic leukemia
T-cell childhood acute lymphoblastic leukemia
cardiac toxicity

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Lymphoma
Leukemia
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Doxorubicin
Liposomal doxorubicin
Dexrazoxane
Methotrexate
Prednisone
Cytarabine
Vincristine
6-Mercaptopurine
Asparaginase
Razoxane
Hydrocortisone-17-butyrate
Hydrocortisone acetate
Hydrocortisone 17-butyrate 21-propionate
Cortisol succinate
Hydrocortisone
Levoleucovorin
Leucovorin
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on October 02, 2014