Combination Chemotherapy and Imatinib Mesylate in Treating Children With Relapsed Acute Lymphoblastic Leukemia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00049569
First received: November 12, 2002
Last updated: October 7, 2013
Last verified: October 2013
  Purpose

Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Combining more than one chemotherapy drug with imatinib mesylate may kill more cancer cells. Randomized phase II trial to study the effectiveness of combination chemotherapy and imatinib mesylate in treating children who have relapsed acute lymphoblastic leukemia.


Condition Intervention
L1 Childhood Acute Lymphoblastic Leukemia
L2 Childhood Acute Lymphoblastic Leukemia
Non-T, Non-B Childhood Acute Lymphoblastic Leukemia
Recurrent Childhood Acute Lymphoblastic Leukemia
T-cell Childhood Acute Lymphoblastic Leukemia
Drug: cytarabine
Drug: methotrexate
Drug: vincristine sulfate
Drug: prednisone
Drug: pegaspargase
Drug: doxorubicin hydrochloride
Drug: imatinib mesylate
Drug: cyclophosphamide
Drug: etoposide
Biological: filgrastim
Drug: leucovorin calcium
Drug: asparaginase
Drug: therapeutic hydrocortisone

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Intensive Induction Therapy for Children With Acute Lymphoblastic Leukemia (ALL) Who Experience a Bone Marrow Relapse

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Feasibility assessed by excessive early deaths, induction failures, and early relapses [ Time Frame: Up to 4 months ] [ Designated as safety issue: Yes ]
  • Toxicity assessed using CTC version 2.0 [ Time Frame: Up to 4 months ] [ Designated as safety issue: Yes ]
    Will be tabulated in detail.


Secondary Outcome Measures:
  • Overall remission reinduction (CR2) rate [ Time Frame: Up to 4 months ] [ Designated as safety issue: No ]
  • EFS [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    The Kaplan-Meier method will be used.

  • MRD [ Time Frame: Up to 4 months ] [ Designated as safety issue: No ]
    The percentage of MRD positive patients will be estimated at the end of each block. Cox regression will be utilized to correlate MRD values with EFS.

  • Feasibility of combining intensive re-induction therapy with imatinib mesylate [ Time Frame: Up to 4 months ] [ Designated as safety issue: No ]
    Will be determined using descriptive statistics due to the small sample size.

  • Percentage of patients who were able to complete the triple re-induction therapy with imatinib mesylate [ Time Frame: Up to 4 months ] [ Designated as safety issue: No ]
    Will be estimated.


Estimated Enrollment: 126
Study Start Date: January 2003
Primary Completion Date: March 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
See detailed description.
Drug: cytarabine
Given IT
Drug: methotrexate
Given IT
Drug: vincristine sulfate
Given IV
Drug: prednisone
Given PO
Drug: pegaspargase
Given IM
Drug: doxorubicin hydrochloride
Given IV
Drug: imatinib mesylate
Given PO
Drug: cyclophosphamide
Given IV
Drug: etoposide
Given IV
Biological: filgrastim
Given SC
Drug: leucovorin calcium
Given IV
Drug: asparaginase
Given IM
Experimental: Arm II
See detailed description.
Drug: cytarabine
Given IT
Drug: methotrexate
Given IT
Drug: vincristine sulfate
Given IV
Drug: prednisone
Given PO
Drug: pegaspargase
Given IM
Drug: doxorubicin hydrochloride
Given IV
Drug: imatinib mesylate
Given PO
Drug: cyclophosphamide
Given IV
Drug: etoposide
Given IV
Biological: filgrastim
Given SC
Drug: leucovorin calcium
Given IV
Drug: asparaginase
Given IM
Drug: therapeutic hydrocortisone
Given IT

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with acute lymphoblastic leukemia (ALL) in first relapse involving the bone marrow (M3 marrow), with or without associated extramedullary disease; this includes patients who are Philadelphia chromosome-positive
  • Shortening fraction of >= 28% by echocardiogram, or ejection fraction of >= 50% by gated radionuclide study
  • Cumulative prior anthracycline exposure of =< 350 mg/m^2 (each 10 mg/m^2 dose of idarubicin should be calculated as the isotoxic equivalent of 50 mg/m^2 of daunorubicin or adriamycin)
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria:

  • Patients with B-cell ALL (L3 morphology or evidence of myc translocation by molecular or cytogenetic technique) are not eligible
  • Patients with Down syndrome are excluded due to the administration of methotrexate in Block 2
  • Patients who have undergone prior stem cell transplantation (SCT) are ineligible if:

    • They received SCT less than 12 months prior to study entry
    • They are still receiving immunosuppression for the treatment of graft-versus-host disease (GVHD)
    • They have active fungal infection at time of study entry
    • They have had invasive filamentous fungal infection at any time post-SCT
  • Pregnant or lactating females are ineligible as the medications used in this protocol could be harmful to unborn children and infants
  • Patients with prior isolated extramedullary relapse are ineligible
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00049569

Locations
United States, California
Children's Oncology Group
Arcadia, California, United States, 91006-3776
Sponsors and Collaborators
Investigators
Principal Investigator: Elizabeth Raetz Children's Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00049569     History of Changes
Other Study ID Numbers: NCI-2012-01798, NCI-2012-01798, COG-AALL01P2, CDR0000258120, AALL01P2, AALL01P2, U10CA098543
Study First Received: November 12, 2002
Last Updated: October 7, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Methotrexate
Imatinib
Pegaspargase
Liposomal doxorubicin
Asparaginase
Vincristine
Doxorubicin
Levoleucovorin
Hydrocortisone-17-butyrate
Hydrocortisone acetate
Hydrocortisone 17-butyrate 21-propionate
Cortisol succinate
Hydrocortisone
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating

ClinicalTrials.gov processed this record on September 30, 2014