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: March 6, 2014
Last verified: November 2013
  Purpose

This phase II trial is studying 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. Combining imatinib mesylate with chemotherapy and peripheral stem cell transplantation may be an effective treatment for acute lymphoblastic leukemia (ALL)


Condition Intervention Phase
Adult Acute Lymphoblastic Leukemia in Remission
Drug: imatinib mesylate
Biological: filgrastim
Drug: methotrexate
Drug: tacrolimus
Drug: cytarabine
Drug: etoposide
Drug: cyclophosphamide
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
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, IND #61135), 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: November 2013
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Patients with HLA-matched sibling donor
Patients undergo courses I-IV as in Detailed Description. Beginning 3-10 days after completion of course IV, patients with an HLA-matched sibling donor undergo total body irradiation (TBI) 2-3 times daily on days -7 to -4. Patients receive etoposide IV over 4 hours on day -3. Patients then undergo PBSCT on day 0. Patients then receive graft-vs-host disease prophylaxis with tacrolimus IV continuously on days -1 to 56 (or IV continuously on days -1 to 14 and then PO or IV every 12 hours on days 15-56) followed by a taper. Patients also receive methotrexate IV on days 1, 3, and 6, and filgrastim (G-CSF) subcutaneously (SC) beginning on day 4 and continuing until blood counts recover. Patients then undergo course VI as in Detailed Description.
Drug: imatinib mesylate
Given PO
Other Names:
  • CGP 57148
  • Gleevec
  • Glivec
Biological: filgrastim
Given SC
Other Names:
  • G-CSF
  • Neupogen
Drug: methotrexate
Given IV
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: tacrolimus
Given IV or PO
Other Names:
  • FK 506
  • Prograf
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Experimental: Patients without HLA-matched sibling donors
Patients undergo courses I-IV as in Detailed Description. Beginning 3-10 days after completion of course IV, patients without an HLA-matched sibling donor receive etoposide IV continuously and cytarabine IV over 2 hours on days 1-4. Patients also receive G-CSF SC beginning on day 14 and continuing until PBSC collection is complete. Patients receive imatinib mesylate PO twice daily beginning after completion of PBSC collection and continuing until 3 days before PBSCT. Patients then undergo TBI 2-3 times daily on days -8 to -5. Patients receive etoposide IV over 4 hours on day -4 and cyclophosphamide IV over 2 hours on day -2. Patients undergo PBSCT on day 0. Patients receive G-CSF SC beginning on day 0 and continuing until blood counts recover. Patients then undergo course VI as in Detailed Description.
Drug: imatinib mesylate
Given PO
Other Names:
  • CGP 57148
  • Gleevec
  • Glivec
Biological: filgrastim
Given SC
Other Names:
  • G-CSF
  • Neupogen
Drug: methotrexate
Given IV
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: cytarabine
Given IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Experimental: Patients who are not transplant candidates
Patients undergo courses I-IV as in Detailed Description. Beginning 3-10 days after completion of course IV, patients who are not candidates for PBSCT receive etoposide IV over 4 hours and cytarabine IV over 2 hours on days 1-4. Patients also receive G-CSF SC once or twice a day beginning on day 14 and continuing until blood counts recover. Patients then undergo course VI as in Detailed Description.
Drug: imatinib mesylate
Given PO
Other Names:
  • CGP 57148
  • Gleevec
  • Glivec
Biological: filgrastim
Given SC
Other Names:
  • G-CSF
  • Neupogen
Drug: methotrexate
Given IV
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: cytarabine
Given IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed acute lymphoblastic leukemia (ALL)
  • Disease in complete or partial remission after 1 course of induction chemotherapy comprising 1 of the following: intensive 4- or 5-drug regimen on a CALGB or SWOG ALL protocol for previously untreated ALL; any standard induction regimen without enrollment on a cooperative group frontline protocol
  • BCR-ABL positive by reverse transcriptase-polymerase chain reaction or fluorescent in situ hybridization OR detection of t(9;22)(q34;q22) or 3-way variant by metaphase cytogenetics
  • All patients must also be enrolled on protocol CLB-9862
  • Absolute neutrophil count at least 1,000/mm^3
  • Platelet count at least 100,000/mm^3
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after study participation
  • No other concurrent chemotherapy
  • No concurrent steroids except for adrenal failure
  • No concurrent hormonal therapy except for non-disease-related conditions (e.g., insulin for diabetes)
  • No concurrent palliative radiotherapy except whole-brain irradiation for documented CNS disease
  • No more than 6 weeks of prior imatinib mesylate during induction therapy
  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 98 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, CALGB 10001/SWOG C10001, U10CA031946
Study First Received: June 6, 2002
Results First Received: November 27, 2013
Last Updated: March 6, 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
Etoposide
Etoposide phosphate
Imatinib
Methotrexate
Tacrolimus
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Alkylating Agents
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Antiviral Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists

ClinicalTrials.gov processed this record on October 30, 2014