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Pilot Trial of Clofarabine Added to Standard Busulfan and Fludarabine for Conditioning Prior to Allogeneic Hematopoietic Cell Transplantation

This study has suspended participant recruitment.
(Triggering of futility rule, requires study modification)
Sponsor:
Information provided by (Responsible Party):
Christopher Dvorak, University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01596699
First received: May 7, 2012
Last updated: August 14, 2014
Last verified: August 2014

May 7, 2012
August 14, 2014
July 2012
June 2018   (final data collection date for primary outcome measure)
Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Participants will be followed for the duration of treatment, an expected average of 5 years. ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01596699 on ClinicalTrials.gov Archive Site
  • Change in the engraftment rate of patients with non-malignant diseases (Stratum A) undergoing allogeneic HCT as compared to historic controls [ Time Frame: Participants will have engraftment blood studies starting approximately Day 30 post hematopoietic stem cell transplant and then monthly until stable. Average study participation is approximately 5 years. ] [ Designated as safety issue: No ]
  • Change in the full donor chimerism of patients with high-risk myeloid malignancies (Stratum B) undergoing allogeneic HCT as compared to historic controls [ Time Frame: Participants will have peripheral blood chimerism assessed at Day 100 post hematopoietic stem cell transplant and then monthly until stable. ] [ Designated as safety issue: No ]
  • Serum concentrations and potential for drug-drug interaction of Fludarabine and Clofarabine [ Time Frame: Pharmacokinetics blood sampling Days -5 to -2 pre-hematopoietic stem cell transplant. ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Pilot Trial of Clofarabine Added to Standard Busulfan and Fludarabine for Conditioning Prior to Allogeneic Hematopoietic Cell Transplantation
A Pilot Trial of Clofarabine Added to Standard Busulfan and Fludarabine for Conditioning Prior to Allogeneic Hematopoietic Cell Transplantation

The purpose of this study is to find out what effects, good and/or bad, the addition of clofarabine, a new chemotherapy agent, to a standard busulfan and fludarabine conditioning treatment has. The study will also look at what causes some people to have high drug levels of these medications in their body compared to other people that may have low drug levels even if they all receive the same dose of medication.

Not Provided
Interventional
Not Provided
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Myeloid Malignancy
  • Bone Marrow Failure Syndrome
  • Transfusion-dependent Red Blood Cell (RBC) Defect
  • Congenital Immunodeficiency
  • Metabolic Disease
  • Severe Immune Dysregulation
  • Drug: Alemtuzumab
    0.5 mg/kg (max 15 mg or max 6 mg), IV, Day -12 to Day -10 pre-HCT
    Other Name: Campath
  • Drug: Busulfan
    0.8 mg/kg/dose q6hrs or 1.1 mg/kg/dose q6hrs, IV, Day -9 to Day -6 pre-HCT
    Other Name: Busulfex
  • Drug: Fludarabine
    40 mg/m2 or 1.33 mg/kg, IV, Day -5 to Day -2 pre-HCT
    Other Name: Fludara
  • Drug: Clofarabine
    10 mg/m2 or 0.33 mg/kg, IV, Day -5 to Day -2 pre-HCT
    Other Name: Clolar
  • Experimental: Patients with Myeloid Malignancies
    Interventions:
    • Drug: Busulfan
    • Drug: Fludarabine
    • Drug: Clofarabine
  • Experimental: Patients with Non-Malignancies
    Interventions:
    • Drug: Alemtuzumab
    • Drug: Busulfan
    • Drug: Fludarabine
    • Drug: Clofarabine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Suspended
31
June 2019
June 2018   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients must be ≥ 3 months and ≤30 years of age.
  • Stratum A: Non-Malignant Diseases, including:

    • Bone Marrow Failure Syndromes
    • Hemoglobinopathies or transfusion-dependent RBC defects
    • Congenital Immunodeficiencies
    • Metabolic Diseases known to be treatable with HCT (e.g. Hurler's)
    • Other Bone Marrow Stem Cell Defects (e.g. Osteopetrosis)
    • Severe Immune Dysregulation / Autoimmune Syndromes with at least transient prior response to immunosuppressive therapy
  • Stratum B: Myeloid Malignancies, including:

    • AML, in greater than first clinical remission, or in CR1 but with detectable disease (≥0.1% Blasts by MRD or Flow, or Positive Cytogenetics), or in CR1 but with a matched sibling UCB donor.
    • MDS
    • JMML
    • CML, with detectable disease by PCR
  • Patients must have a suitable donor based on the UCSF Pediatric BMT SOP. 10/10 (HLA-A, -B, -C, -DR, -DQ) matching will be done for related and adult unrelated donors; 8/8 (HLA-A, -B, -C, -DR) for umbilical cord blood donors. Patients with non-malignant diseases will generally be eligible only if they have a mismatched donor, or an accepted clinical reason to be considered high-risk for rejection.
  • Liver transaminases (AST/ALT) and Direct Bilirubin less than twice the upper limit of normal within 2 weeks of admission.
  • Cardiac Shortening Fraction ≥27% within 4 weeks of admission.
  • Creatinine clearance by Schwartz formula, GFR or 24 hr urine collection ≥50 cc/min/1.73 m2, within 4 weeks of admission.
  • Pulmonary diffusion capacity ≥50% of predicted corrected for anemia/lung volume within 4 weeks of admission. If unable to do PFT's, then no active lung disease by CXR and/or O2 Sat ≥90% on room air.

Exclusion Criteria:

  • Fanconi Anemia
  • Dyskeratosis Congenita
  • A known syndrome with increased sensitivity to radiation or alkylating agents
  • Severe Combined Immunodeficiency Disease eligible for a non-myeloablative HCT trial
  • A mismatched donor for whom ex vivo T-cell depletion of the donor stem cells is planned
Both
3 Months to 30 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01596699
UCSF Protocol No. 110819
Yes
Christopher Dvorak, University of California, San Francisco
Christopher Dvorak
Not Provided
Principal Investigator: Christopher C Dvorak, MD University of California, San Francisco
University of California, San Francisco
August 2014

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