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

NCT ID: NCT01230983

Last Updated: 2013-06-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

573 participants

Study Classification

INTERVENTIONAL

Study Start Date

1996-06-30

Study Completion Date

2004-10-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Cardiac Toxicity Leukemia Lymphoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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)

Group Type EXPERIMENTAL

asparaginase

Intervention Type DRUG

Given IV

cytarabine

Intervention Type DRUG

Given IV

doxorubicin hydrochloride

Intervention Type DRUG

Given IV

mercaptopurine

Intervention Type DRUG

Given orally

methotrexate

Intervention Type DRUG

Given IV

prednisone

Intervention Type DRUG

Given orally

therapeutic hydrocortisone

Intervention Type DRUG

Given IT

vincristine sulfate

Intervention Type DRUG

Given IV

radiation therapy

Intervention Type RADIATION

Radiation to cranium

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)

Group Type ACTIVE_COMPARATOR

asparaginase

Intervention Type DRUG

Given IV

cytarabine

Intervention Type DRUG

Given IV

dexrazoxane hydrochloride

Intervention Type DRUG

Given IV

doxorubicin hydrochloride

Intervention Type DRUG

Given IV

mercaptopurine

Intervention Type DRUG

Given orally

methotrexate

Intervention Type DRUG

Given IV

prednisone

Intervention Type DRUG

Given orally

therapeutic hydrocortisone

Intervention Type DRUG

Given IT

vincristine sulfate

Intervention Type DRUG

Given IV

radiation therapy

Intervention Type RADIATION

Radiation to cranium

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)

Group Type ACTIVE_COMPARATOR

asparaginase

Intervention Type DRUG

Given IV

cytarabine

Intervention Type DRUG

Given IV

doxorubicin hydrochloride

Intervention Type DRUG

Given IV

leucovorin calcium

Intervention Type DRUG

Given IV

mercaptopurine

Intervention Type DRUG

Given orally

methotrexate

Intervention Type DRUG

Given IV

prednisone

Intervention Type DRUG

Given orally

therapeutic hydrocortisone

Intervention Type DRUG

Given IT

vincristine sulfate

Intervention Type DRUG

Given IV

radiation therapy

Intervention Type RADIATION

Radiation to cranium

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)

Group Type ACTIVE_COMPARATOR

asparaginase

Intervention Type DRUG

Given IV

cytarabine

Intervention Type DRUG

Given IV

dexrazoxane hydrochloride

Intervention Type DRUG

Given IV

doxorubicin hydrochloride

Intervention Type DRUG

Given IV

leucovorin calcium

Intervention Type DRUG

Given IV

mercaptopurine

Intervention Type DRUG

Given orally

methotrexate

Intervention Type DRUG

Given IV

prednisone

Intervention Type DRUG

Given orally

therapeutic hydrocortisone

Intervention Type DRUG

Given IT

vincristine sulfate

Intervention Type DRUG

Given IV

radiation therapy

Intervention Type RADIATION

Radiation to cranium

Interventions

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asparaginase

Given IV

Intervention Type DRUG

cytarabine

Given IV

Intervention Type DRUG

dexrazoxane hydrochloride

Given IV

Intervention Type DRUG

doxorubicin hydrochloride

Given IV

Intervention Type DRUG

leucovorin calcium

Given IV

Intervention Type DRUG

mercaptopurine

Given orally

Intervention Type DRUG

methotrexate

Given IV

Intervention Type DRUG

prednisone

Given orally

Intervention Type DRUG

therapeutic hydrocortisone

Given IT

Intervention Type DRUG

vincristine sulfate

Given IV

Intervention Type DRUG

radiation therapy

Radiation to cranium

Intervention Type RADIATION

Other Intervention Names

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E. coli Elspar NSC #10922 Cytosine Arabinoside AraC Cytosar NSC #06387 DZR ADR-529 ZINECARD ICRF-187 NSC #169780 Doxorubicin NSC #123127 LCV Wellcovorin citrovorum factor folinic acid NSC #003590 6-MP Purinethol NSC #000755 MTX amethopterin NSC #000740 Deltasone Meticorten Liquid Pred NSC #010023 hydrocortisone sodium succinate Solu-cortef NSC #010483 VCR Oncovin NSC #067574 XRT

Eligibility Criteria

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Inclusion Criteria

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
Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Children's Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Barbara L. Asselin, MD

Role: STUDY_CHAIR

James P. Wilmot Cancer Center

References

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Cleaver AL, Beesley AH, Firth MJ, Sturges NC, O'Leary RA, Hunger SP, Baker DL, Kees UR. Gene-based outcome prediction in multiple cohorts of pediatric T-cell acute lymphoblastic leukemia: a Children's Oncology Group study. Mol Cancer. 2010 May 12;9:105. doi: 10.1186/1476-4598-9-105.

Reference Type BACKGROUND
PMID: 20459861 (View on PubMed)

Salzer WL, Devidas M, Carroll WL, Winick N, Pullen J, Hunger SP, Camitta BA. Long-term results of the pediatric oncology group studies for childhood acute lymphoblastic leukemia 1984-2001: a report from the children's oncology group. Leukemia. 2010 Feb;24(2):355-70. doi: 10.1038/leu.2009.261. Epub 2009 Dec 17.

Reference Type BACKGROUND
PMID: 20016527 (View on PubMed)

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.

Reference Type BACKGROUND

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.

Reference Type BACKGROUND

Other Identifiers

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U10CA030969

Identifier Type: NIH

Identifier Source: secondary_id

View Link

POG-9404

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000064664

Identifier Type: OTHER

Identifier Source: secondary_id

9404

Identifier Type: -

Identifier Source: org_study_id

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