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S0530 Cytarabine and Clofarabine in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00337168
Recruitment Status : Completed
First Posted : June 15, 2006
Results First Posted : July 10, 2012
Last Update Posted : March 25, 2015
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Southwest Oncology Group

Tracking Information
First Submitted Date  ICMJE June 13, 2006
First Posted Date  ICMJE June 15, 2006
Results First Submitted Date  ICMJE June 5, 2012
Results First Posted Date  ICMJE July 10, 2012
Last Update Posted Date March 25, 2015
Study Start Date  ICMJE October 2006
Actual Primary Completion Date December 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 13, 2013)
Number of Patients With Complete Remission [ Time Frame: Between day 28 and day 35 inclusive ]
Complete remission is defined as: less than 5% bone marrow blasts, neutrophils greater or equal to 1,000 per microliter, platelets greater than 100,000 per microliter, no blasts in the peripheral blood, and no extramedullary disease
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00337168 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 12, 2013)
  • Expression of Nucleoside Transporters [ Time Frame: On average, two weeks before treatment started ]
    Expression was examined in paraffin-embedded tissue by immunohistochemistry. Intensities were scored on a 0-2+ scale. High expression was a score of 2+.
  • Number of Patients With Very Poor Risk Cytogenetics [ Time Frame: On average, 2 weeks before treatment started ]
  • Toxicity [ Time Frame: Patients were assess for adverse events after each induction cycle (up to two cycles) and after the one consolidation cycle ]
    Number of patients with Grade 3-5 adverse events that are related to study drug by given type of adverse event
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 S0530 Cytarabine and Clofarabine in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia
Official Title  ICMJE A Phase II Trial of Cytarabine and Clofarabine in Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL)
Brief Summary

RATIONALE: Drugs used in chemotherapy, such as cytarabine and clofarabine, 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) may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving cytarabine together with clofarabine works in treating patients with relapsed or refractory acute lymphoblastic leukemia.

Detailed Description

Primary objective:

  • Determine whether the complete remission rate in adult patients with relapsed or refractory acute lymphoblastic leukemia (ALL) is sufficiently high after treatment with cytarabine and clofarabine to warrant further investigation.

Secondary objectives:

  • Estimate the frequency and severity of toxicities associated with this dosing schedule of cytarabine and clofarabine.
  • Investigate, preliminarily, the prognostic effects of cytogenetic features on response to treatment in these patients.

Other objectives (if funding allows):

  • Investigate, preliminarily, the prognostic effects of laboratory correlates (expression of nucleoside transporters, expression of other pertinent genes by tissue microarray) and FISH features on response to treatment in these patients

OUTLINE: This is an open-label, multicenter study.

  • Induction therapy (1 or 2 courses): Patients receive induction therapy comprising clofarabine IV over 1 hour followed 4 hours later by cytarabine IV over 2 hours on days 1-5 (course 1). Patients who achieve a response (5-25% blasts in the bone marrow with a ≥ 50% reduction in blasts from initial bone marrow aspirate) receive 1 more course of induction therapy beginning no later than day 45. Patients who achieve complete remission (< 5% blasts in the bone marrow) after 1 or 2 courses of induction therapy may proceed to consolidation therapy.
  • Consolidation therapy (1 course): Beginning within 60 days after the first day of the last induction therapy, patients may receive consolidation therapy comprising clofarabine IV over 1 hour followed 4 hours later by cytarabine IV over 2 hours on days 1-4.

After completion of study treatment, patients are followed periodically for up to 5 years.

PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Leukemia
Intervention  ICMJE
  • Drug: clofarabine
    Induction: 40mg/m2/d; IV over 1 hr; days 1-5 Re-induction (if necessary): 40mg/m2/d; IV over 1 hr; days 1-5 Consolidation: 40mg/m2/d; IV over 1 hr; days 1-4
  • Drug: cytarabine
    Induction: 1g/m2/d; IV over 2 hrs; days 1-5 Re-induction (if necessary): 1g/m2/d; IV over 2 hrs; days 1-5 Consolidation: 1g/m2/d; IV over 2 hrs; days 1-4
Study Arms  ICMJE Experimental: Induc, ReInduc, Consol, clofarabine, cytarabine
Induction: 40mg/m2/d; IV over 1 hr; days 1-5 Re-induction (if necessary): 40mg/m2/d; IV over 1 hr; days 1-5 Consolidation: 40mg/m2/d; IV over 1 hr; days 1-4
Interventions:
  • Drug: clofarabine
  • Drug: cytarabine
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: June 5, 2012)
36
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE January 2013
Actual Primary Completion Date December 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Prior morphologic diagnosis of acute lymphoblastic leukemia (ALL)

    • No M0, mixed lineage, or L3 (Burkitt's) ALL
  • Refractory to a standard induction regimen OR relapsed after successful prior induction therapy

    • Standard induction regimen is defined as any program of treatment that includes vincristine and prednisone or high-dose cytarabine/mitoxantrone
    • Any number of inductions or remissions allowed
  • Must have evidence of ALL in bone marrow or peripheral blood

    • Immunophenotyping of the blood or bone marrow lymphoblasts must be performed to determine lineage (B cell, T cell, or mixed B/T cell)
    • No extramedullary only disease in the absence of bone marrow or blood involvement
    • Co-expression of myeloid antigens (CD13 and CD33) allowed
  • Patients with Philadelphia chromosome-positive (Ph+) ALL or bcr/abl-positive ALL who were previously eligible for imatinib mesylate treatment must have received imatinib mesylate either alone or in combination with chemotherapy for ALL and must have either failed treatment or been unable to tolerate treatment
  • No CNS involvement as determined by lumbar puncture (for previous CNS history or clinical signs or symptoms of CNS) or by clinical exam (if no previous history or signs/symptoms)
  • Must be registered on SWOG-S9910 and SWOG-9007

PATIENT CHARACTERISTICS:

  • Zubrod performance status 0-2
  • Creatinine ≤ 1.5 times upper limit of normal (ULN)
  • AST or ALT ≤ 1.5 times ULN
  • Bilirubin ≤ 1.5 times ULN
  • No psychiatric disorders that would interfere with study compliance
  • No uncontrolled systemic fungal, bacterial, viral, or other infection
  • No other severe concurrent disease
  • No other serious or poorly controlled medical condition that would preclude study participation
  • No history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that would preclude study participation
  • HIV negative
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No pre-existing motor or sensory neuropathy ≥ grade 2
  • No other prior malignancies, except for the following:

    • Adequately treated basal cell or squamous cell skin cancer
    • In situ cervical cancer
    • Adequately treated stage I or II cancer in complete remission
    • Any other prior cancer for which the patient has been disease free for ≥ 5 years

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Recovered from prior therapy
  • No prior clofarabine
  • More than 2 weeks since prior chemotherapy, major surgery, or other investigational agents
  • More than 6 weeks since prior monoclonal antibodies
  • Prior allogeneic or autologous bone marrow transplant allowed provided the following criteria are met:

    • More than 90 days since transplant
    • No acute graft-versus-host disease (GVHD) ≥ grade 2 OR moderate or severe limited chronic GVHD OR extensive chronic GVHD of any severity
  • Prior maintenance therapy with steroids, vincristine, and/or anti-metabolite agents, such as, but not limited to, mercaptopurine, thioguanine, or methotrexate allowed
  • Concurrent hydroxyurea allowed
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years and older   (Child, Adult, Older 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  
 
Administrative Information
NCT Number  ICMJE NCT00337168
Other Study ID Numbers  ICMJE S0530
U10CA032102 ( U.S. NIH Grant/Contract )
SWOG-S0530 ( Other Identifier: SWOG )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Southwest Oncology Group
Study Sponsor  ICMJE Southwest Oncology Group
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Anjali Advani, MD The Cleveland Clinic
Principal Investigator: Jerry Radich, MD Fred Hutchinson Cancer Research Center
PRS Account Southwest Oncology Group
Verification Date March 2015

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