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

NCT01230983 | Completed Phase 3 DMC

• 4 other identifiers: 9404U10CA030969POG-9404CDR0000064664
• Study Type: interventional
• Target: 573
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Cardiac Toxicity; Leukemia; Lymphoma

Keywords

stage III childhood lymphoblastic lymphoma; stage IV childhood lymphoblastic lymphoma; untreated childhood acute lymphoblastic leukemia; T-cell childhood acute lymphoblastic leukemia; cardiac toxicity

Outcome Measures

Primary Outcomes (1)

• Complete Continuous Remission

  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)

  Time to failure for any cause among patients achieving a complete response

Secondary Outcomes (1)

• Abnormalities in the 31 week and the year 3 echocardiograms

  1 year off therapy

Study Arms (4)

Treatment 1: (No HD MTX / No Zinecard)

EXPERIMENTAL

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; Drug: cytarabine; Drug: doxorubicin hydrochloride; Drug: mercaptopurine; Drug: methotrexate; Drug: prednisone; Drug: therapeutic hydrocortisone; Drug: vincristine sulfate; Radiation: radiation therapy

Treatment 2: (No HD MTX / Zinecard)

ACTIVE COMPARATOR

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; Drug: cytarabine; Drug: dexrazoxane hydrochloride; Drug: doxorubicin hydrochloride; Drug: mercaptopurine; Drug: methotrexate; Drug: prednisone; Drug: therapeutic hydrocortisone; Drug: vincristine sulfate; Radiation: radiation therapy

Treatment 3: (HD MTX / No Zinecard)

ACTIVE COMPARATOR

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; Drug: cytarabine; Drug: doxorubicin hydrochloride; Drug: leucovorin calcium; Drug: mercaptopurine; Drug: methotrexate; Drug: prednisone; Drug: therapeutic hydrocortisone; Drug: vincristine sulfate; Radiation: radiation therapy

Treatment 4: (HD MTX / Zinecard)

ACTIVE COMPARATOR

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; 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

Interventions

asparaginase DRUG

Given IV

Also known as: E. coli, Elspar, NSC #10922

Treatment 1: (No HD MTX / No Zinecard); Treatment 2: (No HD MTX / Zinecard); Treatment 3: (HD MTX / No Zinecard); Treatment 4: (HD MTX / Zinecard)

cytarabine DRUG

Given IV

Also known as: Cytosine Arabinoside, AraC, Cytosar, NSC #06387

Treatment 1: (No HD MTX / No Zinecard); Treatment 2: (No HD MTX / Zinecard); Treatment 3: (HD MTX / No Zinecard); Treatment 4: (HD MTX / Zinecard)

dexrazoxane hydrochloride DRUG

Given IV

Also known as: DZR, ADR-529, ZINECARD, ICRF-187, NSC #169780

Treatment 2: (No HD MTX / Zinecard); Treatment 4: (HD MTX / Zinecard)

doxorubicin hydrochloride DRUG

Given IV

Also known as: Doxorubicin, NSC #123127

Treatment 1: (No HD MTX / No Zinecard); Treatment 2: (No HD MTX / Zinecard); Treatment 3: (HD MTX / No Zinecard); Treatment 4: (HD MTX / Zinecard)

leucovorin calcium DRUG

Given IV

Also known as: LCV, Wellcovorin, citrovorum factor, folinic acid, NSC #003590

Treatment 3: (HD MTX / No Zinecard); Treatment 4: (HD MTX / Zinecard)

mercaptopurine DRUG

Given orally

Also known as: 6-MP, Purinethol, NSC #000755

Treatment 1: (No HD MTX / No Zinecard); Treatment 2: (No HD MTX / Zinecard); Treatment 3: (HD MTX / No Zinecard); Treatment 4: (HD MTX / Zinecard)

methotrexate DRUG

Given IV

Also known as: MTX, amethopterin, NSC #000740

Treatment 1: (No HD MTX / No Zinecard); Treatment 2: (No HD MTX / Zinecard); Treatment 3: (HD MTX / No Zinecard); Treatment 4: (HD MTX / Zinecard)

prednisone DRUG

Given orally

Also known as: Deltasone, Meticorten, Liquid Pred, NSC #010023

Treatment 1: (No HD MTX / No Zinecard); Treatment 2: (No HD MTX / Zinecard); Treatment 3: (HD MTX / No Zinecard); Treatment 4: (HD MTX / Zinecard)

therapeutic hydrocortisone DRUG

Given IT

Also known as: hydrocortisone sodium succinate, Solu-cortef, NSC #010483

Treatment 1: (No HD MTX / No Zinecard); Treatment 2: (No HD MTX / Zinecard); Treatment 3: (HD MTX / No Zinecard); Treatment 4: (HD MTX / Zinecard)

vincristine sulfate DRUG

Given IV

Also known as: VCR, Oncovin, NSC #067574

Treatment 1: (No HD MTX / No Zinecard); Treatment 2: (No HD MTX / Zinecard); Treatment 3: (HD MTX / No Zinecard); Treatment 4: (HD MTX / Zinecard)

radiation therapy RADIATION

Radiation to cranium

Also known as: XRT

Treatment 1: (No HD MTX / No Zinecard); Treatment 2: (No HD MTX / Zinecard); Treatment 3: (HD MTX / No Zinecard); Treatment 4: (HD MTX / Zinecard)

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Related Publications (4)

• 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.

  PMID: 20459861 BACKGROUND

• 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.

  PMID: 20016527 BACKGROUND

• 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.

  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.

  BACKGROUND

MeSH Terms

Conditions

Cardiotoxicity; Leukemia; Lymphoma

Interventions

Asparaginase; Cytarabine; Dexrazoxane; Razoxane; Doxorubicin; Leucovorin; Mercaptopurine; Methotrexate; Prednisone; Hydrocortisone; hydrocortisone hemisuccinate; Vincristine; Radiotherapy

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Amidohydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Diketopiperazines; Piperazines; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Sulfhydryl Compounds; Sulfur Compounds; Purines; Aminopterin; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnenediones; Pregnenes; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines; Therapeutics

Study Officials

• Barbara L. Asselin, MD

  James P. Wilmot Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2010
• First Posted: October 29, 2010
• Study Start: June 1, 1996
• Primary Completion: September 1, 2001
• Study Completion: October 1, 2004
• Last Updated: June 6, 2013

Record last verified: 2013-06