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Trial record 49 of 170 for:    "Acute Lymphocytic Leukemia" | "Etoposide"

Combination Chemotherapy With or Without Peripheral Stem Cell Transplant in Treating Children With Acute Lymphoblastic Leukemia

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ClinicalTrials.gov Identifier: NCT00022737
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : February 27, 2014
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE August 10, 2001
First Posted Date  ICMJE January 27, 2003
Last Update Posted Date February 27, 2014
Study Start Date  ICMJE October 2002
Actual Primary Completion Date October 2006   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 14, 2012)
  • Feasibility, in terms of patient accrual [ Time Frame: Up to 1.75 years ]
    As a target goal, we wish to enroll at least 80% of the potential available patients. The accrual duration for this pilot study will be based on accruing adequate numbers to complete the dose escalation study in the Ph+ subset. The planned study accrual duration should be approximately 1.75 years.
  • Feasibility, in terms of incidence of adverse events graded according to NCI CTC v 2.0 [ Time Frame: Up to 7 years ]
    The use of imatinib as given in combination with other agents in a particular cohort will be considered feasible initially if 5 or more of the first 6 evaluable patients complete the phase(s) without evidence of grade 3 or 4 targeted toxicities.
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00022737 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 14, 2012)
Event-free survival [ Time Frame: Up to 7 years ]
Estimated with 90% confidence interval.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Combination Chemotherapy With or Without Peripheral Stem Cell Transplant in Treating Children With Acute Lymphoblastic Leukemia
Official Title  ICMJE A Children's Oncology Group Pilot Study for the Treatment of Very High Risk Acute Lymphoblastic Leukemia in Children and Adolescents (Imatinib (STI571, GLEEVEC) NSC#716051)
Brief Summary This phase II trial is studying how well combination chemotherapy with or without donor peripheral stem cell transplant works in treating children with acute lymphoblastic leukemia. Giving combination chemotherapy before a donor peripheral stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.
Detailed Description

PRIMARY OBJECTIVES:

I. Determine the feasibility of treatment with intensified chemotherapy, in terms of toxicity and patient accrual, in children with very high-risk acute lymphoblastic leukemia.

II. Determine the feasibility and efficacy of following intensified chemotherapy with allogeneic hematopoietic stem cell transplantation in patients with HLA-matched related donors.

III. Determine the toxicity of imatinib mesylate in combination with intensified chemotherapy in Philadelphia chromosome-positive patients.

IV. Determine the event-free survival of patients treated with this regimen. V. Determine whether minimal residual disease (MDR) after induction therapy and prior to intensification therapy can predict relapse in these patients.

VI. Determine whether MDR after intensification is prognostically significant. VII. Determine whether gene expression patterns predict disease recurrence or response to imatinib mesylate.

OUTLINE: This is a multicenter study. This is also a dose-escalation study of imatinib mesylate in Philadelphia chromosome-positive (Ph+) patients. Patients are stratified according to Philadelphia chromosome (Ph) status (Ph-positive vs Ph-negative or indeterminate), hypodiploidy (yes vs no), MLL translocation (11q23) AND slow early response to prior induction therapy (yes vs no), and failed prior induction therapy (yes vs no).

Cohorts of 8-12 Ph+ patients receive escalating doses of imatinib mesylate, according to the guidelines for each treatment block of this study, until the maximum tolerated dose (MTD) for each treatment combination is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. An additional 35 patients are treated at the MTD.

CONSOLIDATION BLOCK 1: Patients receive etoposide IV over 1 hour followed by ifosfamide IV over 1.5 hours on days 1-5. Patients also receive methotrexate intrathecally on day 1 and filgrastim (G-CSF) subcutaneously (SC) on days 6-15 or until blood counts recover. Patients with CNS 2/3 at diagnosis also receive intrathecal triple therapy comprising methotrexate, hydrocortisone, and cytarabine (ITT) on days 8 and 15. Ph+ patients in cohorts 3, 4, and 5 receive oral imatinib mesylate on days 1-21. Within 4 days of starting consolidation therapy, patients with biopsy-proven testicular leukemia undergo radiotherapy daily for 12 days.

CONSOLIDATION BLOCK 2: Patients receive high-dose methotrexate IV over 24 hours and ITT on day 1 followed by high-dose cytarabine IV over 3 hours, every 12 hours on days 2 and 3. Patients also receive leucovorin calcium IV or orally every 6 hours for 3 doses beginning on day 2, and G-CSF SC on days 4-13 or until blood counts recover. Ph+ patients in cohorts 2, 3, 4, and 5 receive oral imatinib mesylate as in consolidation block 1. Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) proceed to preparative chemotherapy. All other patients proceed to reinduction block 1.

REINDUCTION BLOCK 1: Patients receive vincristine IV on days 1, 8, and 15; daunorubicin IV on days 1 and 2; cyclophosphamide IV over 30 minutes, every 12 hours on days 3 and 4; pegaspargase intramuscularly (IM) on day 4; and ITT on days 1 and 15. Patients also receive oral dexamethasone twice daily on days 1-7 and 15-21 and G-CSF SC on days 5-14 or until blood counts recover. Ph+ patients in cohorts 2, 4, and 5 receive imatinib mesylate as in consolidation block 1.

INTENSIFICATION BLOCK 1: Patients receive high-dose methotrexate IV over 24 hours on days 1 and 15 and ITT on days 1 and 22. Patients also receive leucovorin calcium IV or orally every 6 hours for 3 doses beginning on days 2 and 16. Patients receive etoposide IV over 2 hours followed by cyclophosphamide IV over 30 minutes on days 22-24; G-CSF SC on days 27-36 or until blood counts recover; high-dose cytarabine IV over 3 hours, every 12 hours on days 43 and 44; and asparaginase IM on day 44. Ph+ patients in cohorts 1 and 4 receive oral imatinib mesylate on days 43-63, and patients in cohort 5 receive oral imatinib mesylate on days 1-56.

REINDUCTION BLOCK 2: Patients receive vincristine, daunorubicin, cyclophosphamide, pegaspargase, dexamethasone, and G-CSF as in reinduction block 1. Patients also receive ITT on days 1 and 15. Ph+ patients receive imatinib mesylate as in reinduction block 1.

INTENSIFICATION BLOCK 2: Patients receive methotrexate, leucovorin calcium, etoposide, cyclophosphamide, filgrastim, cytarabine, and asparaginase as in intensification block 1. Ph+ patients receive imatinib mesylate as in intensification block 1.

MAINTENANCE 1: Patients receive high-dose methotrexate IV and leucovorin calcium as in consolidation block 2. Patients also receive ITT and vincristine IV on days 1 and 29; oral dexamethasone twice daily on days 1-5 and 29-33; oral methotrexate on days 8, 15, and 22; oral mercaptopurine on days 8-28; etoposide IV over 2 hours followed by cyclophosphamide IV over 30 minutes on days 29-33; and G-CSF SC on days 34-43. Ph+ patients in cohorts 1-4 receive oral imatinib mesylate on days 29-49 and patients in cohort 5 receive oral imatinib mesylate on days 1-56. Treatment repeats every 8 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE 2: Patients receive vincristine and dexamethasone as in maintenance 1. Beginning on day 1, patients undergo cranial radiotherapy once daily, 5 days a week, for approximately 2 weeks. Patients also receive oral methotrexate on days 8, 15, 22, 29, 36, 43, and 50 and oral mercaptopurine on days 11-56. Ph+ patients in cohorts 1-4 receive oral imatinib mesylate on days 1-21 and 29-49, and patients in cohort 5 receive oral imatinib mesylate on days 1-56.

MAINTENANCE 3: Patients receive vincristine and dexamethasone as in maintenance 2. Patients also receive oral methotrexate on days 1, 8, 15, 22, 29, 36, 43, and 50; and oral mercaptopurine on days 1-56. Ph+ patients receive imatinib mesylate as in maintenance 2. Treatment repeats every 8 weeks for 7 courses (12 courses total in maintenance 1, 2, and 3) in the absence of disease progression or unacceptable toxicity.

Patients may undergo allogeneic HSCT after consolidation block 2 if there is an available HLA-DR matched or HLA-A or -B matched or 1 antigen mismatched relative donor.

Patients with CNS leukemia undergo cranial radiotherapy 3 times daily on days -10 to -8. All patients undergo radiotherapy twice daily on days -7 to -5 and receive etoposide IV on day -4 and cyclophosphamide IV on days -3 and -2. Patients undergo allogeneic bone marrow, peripheral blood stem cell, or umbilical cord blood transplantation on day 0. Patients receive cyclosporine IV beginning on day -1 and continuing every 12 hours, switching to oral administration when possible, until day 60 and tapering thereafter. Patients also receive methotrexate on days 1, 3, and 6. Beginning 16-24 weeks after transplantation, Ph+ patients receive oral imatinib mesylate once daily for 24 weeks.

Patients are followed every 4-8 weeks for 1 year, every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter. Patients undergoing HSCT are followed weekly for the first year.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Childhood Acute Lymphoblastic Leukemia in Remission
  • Recurrent Childhood Acute Lymphoblastic Leukemia
Intervention  ICMJE
  • Biological: filgrastim
    Given SC
    Other Names:
    • G-CSF
    • Neupogen
  • Drug: asparaginase
    Given IM
    Other Names:
    • ASNase
    • Colaspase
    • Crasnitin
    • Elspar
    • L-ASP
  • Drug: cyclophosphamide
    Given IV
    Other Names:
    • CPM
    • CTX
    • Cytoxan
    • Endoxan
    • Endoxana
  • Drug: cyclosporine
    Given IV
    Other Names:
    • ciclosporin
    • cyclosporin
    • cyclosporin A
    • CYSP
    • Sandimmune
  • Drug: cytarabine
    Given IT and IV
    Other Names:
    • ARA-C
    • arabinofuranosylcytosine
    • arabinosylcytosine
    • Cytosar-U
    • cytosine arabinoside
  • Drug: daunorubicin hydrochloride
    Given IV
    Other Names:
    • Cerubidin
    • Cerubidine
    • daunomycin hydrochloride
    • daunorubicin
    • RP-13057
  • Drug: dexamethasone
    Given orally
    Other Names:
    • Aeroseb-Dex
    • Decaderm
    • Decadron
    • DM
    • DXM
  • Drug: etoposide
    Given IV
    Other Names:
    • EPEG
    • VP-16
    • VP-16-213
  • Drug: ifosfamide
    Given IV
    Other Names:
    • Cyfos
    • Holoxan
    • IFF
    • IFX
    • IPP
  • Drug: imatinib mesylate
    Given orally
    Other Names:
    • CGP 57148
    • Gleevec
    • Glivec
  • Drug: leucovorin calcium
    Given IV or orally
    Other Names:
    • CF
    • CFR
    • LV
  • Drug: mercaptopurine tablet
    Given orally
    Other Names:
    • 6-mercaptopurine
    • 6-MP
    • Leukerin
    • MP
  • Drug: methotrexate
    Given IT, IV, and orally
    Other Names:
    • amethopterin
    • Folex
    • methylaminopterin
    • Mexate
    • MTX
  • Drug: pegaspargase
    Given IM
    Other Names:
    • L-asparaginase with polyethylene glycol
    • Oncaspar
    • PEG-ASP
    • PEG-L-asparaginase
  • Drug: vincristine sulfate
    Given IV
    Other Names:
    • leurocristine sulfate
    • VCR
    • Vincasar PFS
  • Procedure: allogeneic bone marrow transplantation
    Undergo allogeneic bone marrow, peripheral blood stem cell, or umbilical cord blood transplantation
    Other Names:
    • bone marrow therapy, allogeneic
    • bone marrow therapy, allogenic
    • transplantation, allogeneic bone marrow
    • transplantation, allogenic bone marrow
  • Procedure: peripheral blood stem cell transplantation
    Undergo allogeneic bone marrow, peripheral blood stem cell, or umbilical cord blood transplantation
    Other Names:
    • PBPC transplantation
    • PBSC transplantation
    • peripheral blood progenitor cell transplantation
    • transplantation, peripheral blood stem cell
  • Procedure: umbilical cord blood transplantation
    Undergo allogeneic bone marrow, peripheral blood stem cell, or umbilical cord blood transplantation
    Other Names:
    • cord blood transplantation
    • transplantation, umbilical cord blood
    • UCB transplantation
  • Radiation: radiation therapy
    Undergo radiation therapy
    Other Names:
    • irradiation
    • radiotherapy
    • therapy, radiation
Study Arms  ICMJE Experimental: Arm I
See Design Details.
Interventions:
  • Biological: filgrastim
  • Drug: asparaginase
  • Drug: cyclophosphamide
  • Drug: cyclosporine
  • Drug: cytarabine
  • Drug: daunorubicin hydrochloride
  • Drug: dexamethasone
  • Drug: etoposide
  • Drug: ifosfamide
  • Drug: imatinib mesylate
  • Drug: leucovorin calcium
  • Drug: mercaptopurine tablet
  • Drug: methotrexate
  • Drug: pegaspargase
  • Drug: vincristine sulfate
  • Procedure: allogeneic bone marrow transplantation
  • Procedure: peripheral blood stem cell transplantation
  • Procedure: umbilical cord blood transplantation
  • Radiation: radiation therapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 20, 2007)
220
Original Enrollment  ICMJE Not Provided
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date October 2006   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of acute lymphoblastic leukemia
  • Received prior front-line therapy on a Pediatric Oncology Group (POG),Children's Cancer Group (CCG), or Central Oncology Group (COG) study
  • Received induction therapy comprising vincristine, asparaginase, prednisone/dexamethasone, and daunorubicin as in CCG, POG, or COG protocols
  • M1 or M2 bone marrow status after front-line induction therapy and presenting with at least 1of the following:

    • Philadelphia chromosome positive (Ph+) with t(9;22)(q34;q11) by cytogenetics or fluorescence in situ hybridization
    • bcr-abl fusion transcript by reverse transcription polymerase chain reaction
    • Hypodiploid with less than 44 chromosomes and/or DNA index less than0.81
    • MLL translocation (11q23) by cytogenetics and a slow early response (SER) to induction therapy, defined as at least 5% blasts at day 15 of induction and/or at least .1% minimal residual disease (MRD) after induction therapy
  • Failed to achieve remission after front-line induction therapy

    • M3 bone marrow status (greater than 25% blasts) after induction therapy
    • M2 bone marrow status (5-25% blasts) or at least 1% MRD after induction therapy and M2 or M3or at least 1% MRD after consolidation therapy (CCG studies) or extended induction therapy (POG or COG studies)
  • See Disease Characteristics
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • See Disease Characteristics
  • See Disease Characteristics
  • No concurrent prophylactic cranial radiotherapy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries Australia,   Canada,   Netherlands,   New Zealand,   Puerto Rico,   Switzerland
 
Administrative Information
NCT Number  ICMJE NCT00022737
Other Study ID Numbers  ICMJE NCI-2012-01862
NCI-2012-01862 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000068859
COG-AALL0031
AALL0031 ( Other Identifier: Children's Oncology Group )
AALL0031 ( Other Identifier: CTEP )
U10CA098543 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Kirk Schultz Children's Oncology Group
PRS Account National Cancer Institute (NCI)
Verification Date November 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP