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Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk Acute Lymphoblastic Leukemia

This study is currently recruiting participants.
Verified November 2012 by National Cancer Institute (NCI)
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01406756
First received: July 29, 2011
Last updated: November 22, 2012
Last verified: November 2012
History of Changes
  Purpose

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) and giving the drugs in different doses and in different combinations may kill more cancer cells.

PURPOSE: This randomized phase III trial is studying how well combination chemotherapy works in treating young patients with newly diagnosed high-risk acute lymphoblastic leukemia.


Condition Intervention Phase
Cognitive/Functional Effects
Leukemia
Neurotoxicity
Pain
Therapy-related Toxicity
 Drug: clofarabine
Drug: cyclophosphamide
Drug: cytarabine
Drug: doxorubicin hydrochloride
Drug: etoposide
Drug: hydrocortisone sodium succinate
Drug: leucovorin calcium
Drug: mercaptopurine
Drug: methotrexate
Drug: pegaspargase
Drug: prednisone
Drug: thioguanine
Drug: vincristine sulfate
Radiation: selective external radiation therapy
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III Randomized Trial for Newly Diagnosed High Risk B-precursor Acute Lymphoblastic Leukemia (ALL) Testing Clofarabine (IND# 73789, NSC# 606869) in the Very High Risk Stratum

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 5-year DFS of children with HR-ALL [ Designated as safety issue: No ]
  • 4-year DFS of children, adolescents, and young adults with VHR-ALL [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity and tolerability of post-induction age-adjusted ITT compared to age-adjusted IT MTX in children with HR-ALL [ Designated as safety issue: Yes ]
  • Toxicity and tolerability of arms II and III compared to arm I in patients with VHR-ALL [ Designated as safety issue: Yes ]
  • Increase of ≥ 65% of 5-year DFS and < 10% induction mortality in patients with DS and HR-ALL treated with modified Induction and post-Induction therapy regimen with MBFM-IMIDM [ Designated as safety issue: No ]
  • Toxicity and tolerability of MBFM-IMIDM in children with Down syndrome [ Designated as safety issue: Yes ]
  • Percentage of VHR-ALL patients randomized to control versus experimental arms that attain MRD ≤ 0.01% upon recovery from consolidation [ Designated as safety issue: No ]
  • 5-year OS rate for HR-ALL patients [ Designated as safety issue: No ]
  • 4-year OS rate for VHR-ALL patients [ Designated as safety issue: No ]
  • Prognostic significance of HR genetic lesions and molecular risk classifiers [ Designated as safety issue: No ]

Estimated Enrollment: 4450
Study Start Date: February 2012
Estimated Primary Completion Date: August 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I HR-ALL C
Patients receive consolidation therapy comprising cyclophosphamide IV over 30-60 minutes on days 1 and 29; cytarabine IV or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO on days 1-4 and 29-42, methotrexate IT on days 1, 8, 15, and 22; vincristine sulfate IV on days 15, 22, 43, and 50; and pegaspargase IV over 1-2 hours on days 15 and 43. Patients with continuing clinical evidence of testicular leukemia undergo radiotherapy (RT) once daily, 5 days a week, for approximately 2½ weeks (12 fractions total).
 Drug: cyclophosphamide
Given IV
Drug: cytarabine
Given IT
Drug: mercaptopurine
Given PO
Drug: methotrexate
Given IV
Drug: pegaspargase
Given IV
Drug: vincristine sulfate
Given IV
Radiation: selective external radiation therapy
Radiotherapy
Experimental: Arm II HR-ALL C
Patients receive intrathecal triple therapy (ITT) comprising methotrexate, hydrocortisone sodium succinate, and cytarabine on days 1, 8, 15, and 22. Patients also receive consolidation therapy as patients in arm I HR-ALL C. Patients with testicular leukemia also undergo RT as in arm I HR-ALL C.
 Drug: cyclophosphamide
Given IV
Drug: cytarabine
Given IT
Drug: hydrocortisone sodium succinate
Given IT
Drug: mercaptopurine
Given PO
Drug: methotrexate
Given IV
Drug: pegaspargase
Given IV
Drug: vincristine sulfate
Given IV
Radiation: selective external radiation therapy
Radiotherapy
Active Comparator: Arm I HR-ALL IM
Patients receive interim maintenance (IM) therapy comprising vincristine sulfate IV on days 1, 15, 29, and 43; high-dose methotrexate IV over 24 hours on days 1, 15, 29, and 43; leucovorin calcium PO or IV on days 3-4, 17-18, 31-32, and 45-46; methotrexate IT on days 1 and 29; and mercaptopurine PO on days 1-56.
 Drug: leucovorin calcium
Given IV
Drug: mercaptopurine
Given PO
Drug: methotrexate
Given IV
Drug: vincristine sulfate
Given IV
Experimental: Arm II HR-ALL IM
Patients receive ITT on days 1 and 29 and IM therapy as in arm I HR-ALL IM.
 Drug: cytarabine
Given IT
Drug: hydrocortisone sodium succinate
Given IT
Drug: leucovorin calcium
Given IV
Drug: mercaptopurine
Given PO
Drug: methotrexate
Given IV
Drug: vincristine sulfate
Given IV
Active Comparator: Arm I HR-ALL DI
Patients receive delayed intensification (DI) therapy comprising vincristine sulfate IV on days 1, 8, 15, 43, and 50; dexamethasone PO or IV BID on days 1-7, and 15-21; doxorubicin hydrochloride IV on days 1, 8, and 15; methotrexate IT on days 1, 29, and 36; pegaspargase IV over 1-2 hours on days 4 and 43; cyclophosphamide IV over 30-60 minutes on day 29; cytarabine IV on days 29-32 and 36-39; and thioguanine PO on days 29-42.
 Drug: cyclophosphamide
Given IV
Drug: cytarabine
Given IT
Drug: doxorubicin hydrochloride
Given IV
Drug: methotrexate
Given IV
Drug: pegaspargase
Given IV
Drug: prednisone
Given IV
Drug: thioguanine
Given PO
Drug: vincristine sulfate
Given IV
Experimental: Arm II HR-ALL DI
Patients receive ITT on days 1, 29, and 36 and DI therapy as in arm I HR-ALL DI.
 Drug: cyclophosphamide
Given IV
Drug: cytarabine
Given IT
Drug: doxorubicin hydrochloride
Given IV
Drug: hydrocortisone sodium succinate
Given IT
Drug: methotrexate
Given IV
Drug: pegaspargase
Given IV
Drug: prednisone
Given IV
Drug: thioguanine
Given PO
Drug: vincristine sulfate
Given IV
Active Comparator: Arm I HR-ALL M
Patients receive maintenance therapy comprising vincristine sulfate IV on days 1, 29, and 57; methotrexate IT on days 1 (also day 29 of courses 1-4) ; prednisone PO BID on days 1-5, 29-33, and 57-61; mercaptopurine PO on days 1-84; and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. Treatment repeats every 12 weeks for 2 years (females) or 3 years (males) in the absence of disease progression or unacceptable toxicity.
 Drug: mercaptopurine
Given PO
Drug: methotrexate
Given IV
Drug: vincristine sulfate
Given IV
Experimental: Arm II HR-ALL M
Patients receive ITT on day 1 (also day 29 of courses 1-4) and maintenance therapy as in arm I HR-ALL M. Treatment repeats every 12 weeks for 2 years (females) or 3 years (males) in the absence of disease progression or unacceptable toxicity.
 Drug: cytarabine
Given IT
Drug: hydrocortisone sodium succinate
Given IT
Drug: mercaptopurine
Given PO
Drug: methotrexate
Given IV
Drug: vincristine sulfate
Given IV
Active Comparator: Arm A VHR-ALL C
Patients receive consolidation therapy comprising cyclophosphamide IV over 30-60 minutes on day 29; cytarabine IV over 15-30 minutes or SC on days 29-32 and 36-39; mercaptopurine PO on days 29-42; vincristine IV on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43.
 Drug: cyclophosphamide
Given IV
Drug: cytarabine
Given IT
Drug: mercaptopurine
Given PO
Drug: pegaspargase
Given IV
Drug: vincristine sulfate
Given IV
Experimental: Arm B VHR-ALL C
Patients receive consolidation therapy comprising cyclophosphamide IV over 15-30 minutes on days 29-33; etoposide IV over 1-2 hours on days 29-33; vincristine sulfate IV on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43.
 Drug: cyclophosphamide
Given IV
Drug: etoposide
Given IV
Drug: pegaspargase
Given IV
Drug: vincristine sulfate
Given IV
Experimental: Arm C VHR-ALL C
Patients receive clofarabine IV over 2 hours on days 29-33 and consolidation therapy as in arm B VHR-ALL C.
 Drug: clofarabine
Given IV
Drug: cyclophosphamide
Given IV
Drug: etoposide
Given IV
Drug: pegaspargase
Given IV
Drug: vincristine sulfate
Given IV
Active Comparator: Arm A VHR-ALL DI
Patients receive DI therapy comprising cyclophosphamide IV over 30-60 minutes on day 29; cytarabine IV over 15-30 minutes or SC on days 29-32 and 36-39; thioguanine PO on days 29-42; methotrexate IT on days 29 and 36; vincristine sulfate IV on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43.
 Drug: cyclophosphamide
Given IV
Drug: cytarabine
Given IT
Drug: methotrexate
Given IV
Drug: pegaspargase
Given IV
Drug: thioguanine
Given PO
Drug: vincristine sulfate
Given IV
Experimental: Arm B VHR-ALL DI
Patients receive DI therapy comprising cyclophosphamide IV over 15-30 minutes on days 29-33; etoposide IV over 1-2 hours on days 29-33; methotrexate IT on days 29 and 36; vincristine sulfate IV on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43.
 Drug: cyclophosphamide
Given IV
Drug: etoposide
Given IV
Drug: methotrexate
Given IV
Drug: pegaspargase
Given IV
Drug: vincristine sulfate
Given IV
Experimental: Arm C VHR-ALL DI
Patients receive clofarabine IV over 2 hours on days 29-33 and DI therapy as in arm II B VHR-ALL DI.
 Drug: clofarabine
Given IV
Drug: cyclophosphamide
Given IV
Drug: etoposide
Given IV
Drug: methotrexate
Given IV
Drug: pegaspargase
Given IV
Drug: vincristine sulfate
Given IV

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   1 Year to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Patients must have newly diagnosed B-precursor acute lymphoblastic leukemia (ALL); patients with Down syndrome (DS) are also eligible

  • Patients must have one of the following:

    • NCI high-risk ALL or NCI standard-risk ALL with central nervous system (CNS), testicular leukemia, and/or steroid pre-treatment, and be enrolled in COG AALL08B1; patients that begin therapy on this study (AALL1131) prior to enrollment on COG AALL08B1 are ineligible
    • NCI standard-risk ALL, be enrolled in COG AALL08B1 or COG AALL0932 and completed AALL0932 induction treatment and been classified as high-risk or very high-risk
  • Patients with BCR-ABL1 (Philadelphia chromosome positive) are not eligible for post-induction therapy on this study; non-DS patients may be eligible to enroll in COG AALL0622 or successor COG Ph+ ALL trial by day 15 induction
  • DS HR-ALL patients with induction failure or BCR-ABL1 are not eligible for post-induction

  • No VHR-ALL patients with significant hepatic dysfunction at the time of post-induction randomization defined as:

    • Direct bilirubin > 1.5 times upper limit of normal (ULN) for age
    • SGPT (ALT) ≥ 3 times ULN for age
    • Lipase > 2.0 times ULN for age
  • Patients cannot have secondary ALL that developed after treatment of a prior malignancy with cytotoxic chemotherapy

PATIENT CHARACTERISTICS:

  • White blood cell count (WBC) criteria:

    • Age 1-9.99 years: WBC ≥ 50 000/μL
    • Age 10-30.99 years: Any WBC

    • Age 1-30.99 years: Any WBC with:

      • Testicular leukemia
      • CNS leukemia (CNS3)
      • Steroid pretreatment
  • No very high-risk (VHR) acute lymphoblastic leukemia (ALL) patients with hepatitis B or C infection or history of cirrhosis at the time of post-induction randomization
  • Negative pregnancy test
  • Patients of childbearing potential must agree to use an effective birth control method
  • Female patients who are lactating must agree to stop breast-feeding

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Patients must not have received any prior cytotoxic chemotherapy for the current diagnosis of acute lymphoblastic leukemia (ALL) or any cancer diagnosed previously, with the exception of steroids and intrathecal cytarabine for the current diagnosis of ALL
  • Patients receiving prior steroid therapy may be eligible
  • No concurrent intensity-modulated radiotherapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01406756

  Show 173 Study Locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Principal Investigator: Michael J. Burke, MD Masonic Cancer Center, University of Minnesota
  More Information

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Peter C. Adamson, Children's Oncology Group - Group Chair Office
ClinicalTrials.gov Identifier: NCT01406756     History of Changes
Other Study ID Numbers: CDR0000706370, COG-AALL1131
Study First Received: July 29, 2011
Last Updated: November 22, 2012
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
cognitive/functional effects
pain
neurotoxicity
therapy-related toxicity
B-cell childhood acute lymphoblastic leukemia
 B-cell adult acute lymphoblastic leukemia
Philadelphia chromosome positive childhood precursor acute lymphoblastic leukemia
untreated adult acute lymphoblastic leukemia
untreated childhood acute lymphoblastic leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neurotoxicity Syndromes
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Nervous System Diseases
Poisoning
Substance-Related Disorders
6-Mercaptopurine
Cytarabine
 Methotrexate
Thioguanine
Cyclophosphamide
Etoposide phosphate
Pegaspargase
Clofarabine
Doxorubicin
Etoposide
Prednisone
Vincristine
Cortisol succinate
Hydrocortisone acetate
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone
Hydrocortisone-17-butyrate

ClinicalTrials.gov processed this record on May 22, 2013