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Chemotherapy, Imatinib Mesylate, and Peripheral Stem Cell Transplantation in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00039377
First received: June 6, 2002
Last updated: November 13, 2014
Last verified: June 2014
  Purpose

This phase II trial studies how well giving imatinib mesylate together with chemotherapy and peripheral stem cell transplantation works in treating patients with newly diagnosed acute lymphoblastic leukemia. 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. Giving imatinib mesylate together with chemotherapy and peripheral stem cell transplantation may be an effective treatment for acute lymphoblastic leukemia.


Condition Intervention Phase
Adult Acute Lymphoblastic Leukemia in Remission
Drug: imatinib mesylate
Drug: methotrexate
Drug: vincristine sulfate
Drug: leucovorin calcium
Procedure: peripheral blood stem cell transplantation
Procedure: autologous hematopoietic stem cell transplantation
Procedure: allogeneic hematopoietic stem cell transplantation
Radiation: total-body irradiation
Drug: tacrolimus
Biological: filgrastim
Drug: etoposide
Drug: cyclophosphamide
Drug: cytarabine
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Sequential Chemotherapy, Imatinib Mesylate (Gleevec, STI571) (NSC # 716051), and Transplantation for Adults With Newly Diagnosed Ph+ Acute Lymphoblastic Leukemia by the CALGB and SWOG

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Disease Free Survival [ Time Frame: Duration of treatment (up to 10 years) ] [ Designated as safety issue: No ]

    Disease-free survival (DFS) was measured as the interval from achievement of complete remission (CR) until relapse or death, regardless of cause; patients alive and in CR were censored at last follow-up. DFS was estimated using the Kaplan Meier method.

    A complete remission (CR) was defined as recovery of morphologically normal bone marrow and blood counts (i.e., neutrophils >= 1.5 x 10^9/L and platelets > 100 x 10^9/L) and no circulating leukemic blasts or evidence of extramedullary leukemia and persisting for at least one month.



Secondary Outcome Measures:
  • Overall Survival [ Time Frame: Duration of study (up to 10 years) ] [ Designated as safety issue: No ]
    Overall survival (OS) as the interval from the on-study date until death. OS was estimated using the Kaplan Meier method.

  • Number of Participants Who Achieved a BCR-ABL Response at 12 Months [ Time Frame: 12 months ] [ Designated as safety issue: No ]

    BCR-ABL response is defined in two ways: complete molecular response (CMR) and major molecular response (MMR).

    Complete Molecular Response is defined as a Bcr-Abl (a fusion of gene of Bcr and ABl genes) ratio ≤0.0032% on the International Scale Bcr = breakpoint cluster gene Abl = abelson proto-oncogene

    MMR is defined as Bcr-Abl (A fusion gene of the breakpoint cluster region [Bcr] gene and Abelson proto-oncogene [Abl] genes) transcript ratio ≤0.1% (≥ 3 log reduction of BCR-ABL transcripts from a standardized baseline), as detected by reverse transcriptase polymerase chain reaction [RT-PCR] (performed centrally).


  • 5 Year Disease-free Survival for Autologous & Allogeneic Transplant Groups [ Time Frame: 5 years from CR ] [ Designated as safety issue: No ]
    Percentage of patients who achieved a complete remission (CR) and were alive and relapse free at 5 years. The 5-year progression free survival was estimated using the Kaplan Meier method.

  • 5 Year Overall Survival for Autologous & Allogeneic Transplant Groups [ Time Frame: 5 years from registration ] [ Designated as safety issue: No ]
    Percentage of patients who were alive at 5 years. The 5-year progression free survival was estimated using the Kaplan Meier method.


Enrollment: 58
Study Start Date: April 2002
Study Completion Date: February 2014
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (imatinib mesylate, chemotherapy, PBSCT)
See Detailed Description.
Drug: imatinib mesylate
Given PO
Other Names:
  • CGP 57148
  • Gleevec
  • Glivec
Drug: methotrexate
Given IT and IV
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: leucovorin calcium
Given IV and PO
Other Names:
  • CF
  • CFR
  • LV
Procedure: peripheral blood stem cell transplantation
Undergo PBSCT
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell
Procedure: autologous hematopoietic stem cell transplantation
Undergo autologous PBSCT
Procedure: allogeneic hematopoietic stem cell transplantation
Undergo allogeneic PBSCT
Radiation: total-body irradiation
Undergo TBI
Other Name: TBI
Drug: tacrolimus
Given IV or PO
Other Names:
  • FK 506
  • Prograf
Biological: filgrastim
Given SC
Other Names:
  • G-CSF
  • Neupogen
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: cytarabine
Given IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Other: laboratory biomarker analysis
Correlative studies

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   15 Years to 59 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Unequivocal histologic diagnosis of ALL
  • Detection of the t(9;22)(q34;q11) or 3-way variant by metaphase cytogenetics or BCR-ABL positive by molecular analysis (RT-PCR or fluorescence in situ hybridization [FISH})
  • Prior Therapy:

    • Complete or partial remission following one course of induction chemotherapy with an intensive 4 or 5 drug regimen (with or without imatinib mesylate) on a CALGB or SWOG ALL protocol for previously untreated ALL patients

      • Note: The double induction regimen of SWOG S0333 is considered to be one course of induction chemotherapy for the purpose of this eligibility criterion; therefore, patients from S0333 may be eligible for this study only after completing the entire double induction regimen
    • Complete or partial remission following one course of therapy on any standard induction regimen (with or without imatinib mesylate) without prior enrollment on a cooperative group frontline protocol; in these instances, documentation of Philadelphia chromosome (Ph)+ positivity may occur outside a CALGB or SWOG laboratory

      • Note: CALGB institutions must enroll patients on CALGB 9862 and submission of an initial sample for the companion trial must occur at time of enrollment on CALGB C10001; enrollment on companion studies CALGB 8461 and 9665 is not required
  • No more than six weeks of prior imatinib mesylate during induction therapy before study enrollment
  • Non-pregnant and non-nursing; treatment under this protocol would expose an unborn child to significant risks; women and men of reproductive potential should agree to use an effective means of birth control and contraception should continue for three months after the last dose of imatinib mesylate (Gleevec) to allow complete clearance of drug and its principle metabolites from the body; in women of childbearing potential, a pregnancy test will be required at study entry
  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: NCT00039377

  Show 97 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Meir Wetzler Cancer and Leukemia Group B
  More Information

Publications:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00039377     History of Changes
Obsolete Identifiers: NCT01648426
Other Study ID Numbers: NCI-2009-00436, NCI-2009-00436, CDR0000069378, CALGB 10001/SWOG C10001, CALGB-10001, U10CA031946
Study First Received: June 6, 2002
Results First Received: November 27, 2013
Last Updated: November 13, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Cyclophosphamide
Cytarabine
Imatinib
Levoleucovorin
Methotrexate
Vincristine
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Alkylating Agents
Anti-Infective Agents
Antidotes
Antimetabolites
Antimetabolites, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Antiviral Agents
Dermatologic Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on November 24, 2014