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

This study is currently recruiting participants.
Verified May 2013 by University of California, San Francisco
Sponsor:
Information provided by (Responsible Party):
Christopher Dvorak, University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01596699
First received: May 7, 2012
Last updated: May 16, 2013
Last verified: May 2013
History of Changes
  Purpose

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.


Condition Intervention
Myeloid Malignancy
Bone Marrow Failure Syndrome
Transfusion-dependent Red Blood Cell (RBC) Defect
Congenital Immunodeficiency
Metabolic Disease
Severe Immune Dysregulation
 Drug: Alemtuzumab
Drug: Busulfan
Drug: Fludarabine
Drug: Clofarabine

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Trial of Clofarabine Added to Standard Busulfan and Fludarabine for Conditioning Prior to Allogeneic Hematopoietic Cell Transplantation

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 31
Study Start Date: July 2012
Estimated Study Completion Date: June 2019
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Patients with Myeloid Malignancies 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 Non-Malignancies 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

  Eligibility

Ages Eligible for Study:   3 Months to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01596699

Contacts
Contact: Christopher C Dvorak, MD 415-476-2188 dvorakc@peds.ucsf.edu

Locations
United States, California
UCSF Comprehensive Cancer Center Recruiting
San Francisco, California, United States, 94143
Contact: Sharon S Lee     415-514-3658     LeeSS@peds.ucsf.edu    
Contact: Jueleah Expose-Spenser     415-353-1248     Jueleah.Expose-Spencer@ucsfmedctr.org    
Principal Investigator: Christopher C Dvorak, MD            
Sponsors and Collaborators
Christopher Dvorak
Investigators
Principal Investigator: Christopher C Dvorak, MD University of California, San Francisco
  More Information

No publications provided

Responsible Party: Christopher Dvorak, Assistant Clinical Professor, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01596699     History of Changes
Other Study ID Numbers: UCSF Protocol No. 110819
Study First Received: May 7, 2012
Last Updated: May 16, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, San Francisco:
conditioning
allogeneic
hematopoietic
 cell
transplantation
HCT

Additional relevant MeSH terms:
Neoplasms
Immunologic Deficiency Syndromes
Metabolic Diseases
Pancytopenia
Hemoglobinuria, Paroxysmal
Immune System Diseases
Hematologic Diseases
Anemia, Hemolytic
Anemia
Myelodysplastic Syndromes
Bone Marrow Diseases
Busulfan
Fludarabine monophosphate
Campath 1G
Fludarabine
 Clofarabine
Alemtuzumab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on May 21, 2013