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A Phase I Trial of Myeloablative Conditioning w/ Clofarabine and HD Busulfan for Pts w/ Refractory Heme Malignancies Undergoing Allo PBSCT
This study is currently recruiting participants.
Verified by Indiana University, January 2009
Sponsors and Collaborators: Indiana University School of Medicine
Genzyme
Information provided by: Indiana University
ClinicalTrials.gov Identifier: NCT00477542
  Purpose

This is a phase trial to determine the maximum tolerated dose (MTD) of clofarabine in a combination with a myeloablative dose of busulfan. This is an initial step in developing a novel myeloablative preparative regimen for allogeneic hematopoietic stem cell transplantation (HSCT). While this phase I trial will initially develop the regimen in patients with refractory disease, it is expected that it will find its best application in patients with less advanced disease


Condition Intervention Phase
Hematologic Malignancies
Drug: clofarabine
Phase I

MedlinePlus related topics: Cancer
Drug Information available for: Busulfan Clofarabine
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study
Official Title: A Phase I Trial of Myeloablative Conditioning Using Clofarabine and High-Dose Busulfan for Patients With Refractory Hematological Malignancies Undergoing Allogeneic HSCT

Further study details as provided by Indiana University:

Primary Outcome Measures:
  • Determine the MTD of clofarabine in association with a myeloablative dose of busulfan as a preparative regimen in patients with refractory hematological malignancies undergoing allogeneic HSCT. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • • Assessment of the toxicity of the combination of clofarabine and busulfan • Assess clofarabine and busulfan pharmacokinetics with combination therapy • Describe the response rate • Describe relapse rate and event-free survival [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 18
Study Start Date: May 2007
Estimated Study Completion Date: May 2011
Estimated Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: clofarabine

    Cohort- n- Clofarabine (mg/m2/day)

    -1 3-10 20

    1. 3-6 30
    2. 3-6 40
    3. 3-6 50
    4. 3-6 60
    5. 6-10 70
Detailed Description:

All patients will receive the same dose of busulfan. The dose of clofarabine will be escalated in successive cohorts of patients. Using a standard dose escalation design, successive cohorts of 3 patients will be treated with escalating doses of clofarabine. At the MTD (or highest dose-level if the MTD is not reached), the cohort will be expanded to 10 patients to better investigate correlative studies and give some preliminary idea of efficacy.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Documentation of disease. Patients must have one of the following disease types:

    • Acute myeloid leukemia (AML) with either:

      • Primary refractory to induction chemotherapy
      • Relapsed and refractory AML with >5% blasts in bone marrow or extramedullary disease (excluding active disease of the central nervous system).
      • Patients in second or subsequent complete remission (CR2, CR3, etc.).
    • Acute lymphoblastic leukemia (ALL) with one of the following criteria:

      • Primary refractory to induction chemotherapy.
      • Relapsed and refractory ALL with >5% blasts in bone marrow or extramedullary disease (excluding active disease of the central nervous system).
      • Patients in second or subsequent complete remission (CR2, CR3, etc.).
    • Myelodysplasia, refractory anemia with excess blasts with 11-20% blasts in the bone marrow (RAEB II).
    • Chronic myelogenous leukemia (CML) with one of the following criteria:

      • Accelerated phase.
      • Patients in blast crisis.
    • Patients with aggressive non-Hodgkin's lymphoma (NHL), including diffuse large cell lymphoma, mediastinal B-cell lymphoma, transformed lymphoma, mantle cell lymphoma, and peripheral T cell lymphoma, who also have one of the following criteria:

      • Failure to achieve complete remission to primary induction therapy
      • Relapsed NHL, refractory to at least one line of salvage systemic therapy
  • Patients who relapse < 6 months following autologous stem cell transplantation are not eligible.
  • Patient age 18-60 years
  • Availability of a consenting HLA-matched donor
  • Performance status ECOG 0-1
  • No active infection. Patients with active infections requiring oral or intravenous antibiotics are not eligible for enrollment until resolution of infection.
  • No HIV disease. Patients with immune dysfunction are at a significantly higher risk of infection from intensive immunosuppressive therapies.
  • Non-pregnant and non-nursing. Treatment under this protocol would expose a fetus to significant risks. Women of childbearing potential should have a negative pregnancy test prior to study entry. Women and men of reproductive potential should agree to use an appropriate method of birth control throughout their participation in this study due to the teratogenic potential of the therapy utilized in this trial. Appropriate methods of birth control include oral contraceptives, implantable hormonal contraceptives (Norplant®), or double barrier method (diaphragm plus condom).
  • Required baseline laboratory values:

    • LVEF > 45% corrected
    • DLCO > 50% of predicted value (corrected for hemoglobin)
    • Serum creatinine ≤ 2.0 mg/dl or estimated creatinine clearance of ≥60 ml/min
    • Bilirubin < 1 x upper limit of normal value
    • AST and ALT < 1 x upper limit of normal value
  • Signed written informed consent. Patient must be capable of understanding the investigational nature of the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent.

Exclusion Criteria:

  • Patients who relapse < 6 months following autologous stem cell transplantation are not eligible
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00477542

Contacts
Contact: Lisa Wood, RN 317-274-1781 llwood@iupui.educ
Contact: Sherif Farag, MD, PhD 317-274-0843 ssfarag@iupui.edu

Locations
United States, Indiana
Indiana University Cancer Center Recruiting
Indianapolis, Indiana, United States, 46202
Principal Investigator: Sherif Farag, MD, PhD            
Sponsors and Collaborators
Indiana University School of Medicine
Genzyme
Investigators
Principal Investigator: Sherif Farag, MD, PhD Indiana University
  More Information

IU Cancer Center 'Find a Clinical Trial'  This link exits the ClinicalTrials.gov site

Responsible Party: Indiana University Cancer Center ( Sherif Farag, MD, PhD/ Principal Investigator )
Study ID Numbers: 0704-30 IUCRO-0186
Study First Received: May 21, 2007
Last Updated: January 6, 2009
ClinicalTrials.gov Identifier: NCT00477542  
Health Authority: United States: Institutional Review Board

Keywords provided by Indiana University:
Clofarabine
allogeneic HSCT
refractory malignancies

Study placed in the following topic categories:
Clofarabine
Hematologic Neoplasms
Hematologic Diseases
Busulfan

Additional relevant MeSH terms:
Neoplasms
Neoplasms by Site
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009