Clinical trial NCT01596699: Pilot Trial of Clofarabine Added to Standard Busulfan and Fludarabine for Conditioning Prior to Allogeneic Hematopoietic Cell Transplantation
Official title: A Pilot Trial of Clofarabine Added to Standard Busulfan and Fludarabine for Conditioning Prior to Allogeneic Hematopoietic Cell Transplantation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Myeloid Malignancy
Bone Marrow Failure Syndrome
Transfusion-dependent Red Blood Cell (RBC) Defect
Congenital Immunodeficiency
Metabolic Disease
Severe Immune Dysregulation
Keywords: conditioning
allogeneic
hematopoietic
cell
transplantation
HCT
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
First posted: 2012-05-11
Enrollment: 16
Sex: ALL
Minimum age (years): 3
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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 red blood cell (RBC) defects
  * Congenital Immunodeficiencies
  * Metabolic Diseases known to be treatable with Hematopoietic cell transplantation (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:

  * acute myeloid leukemia (AML), in greater than first clinical remission, or in CR1 but with detectable disease (≥0.1% Blasts by minimal residual disease (MRD) or Flow, or Positive Cytogenetics), or in CR1 but with a matched sibling Umbilical cord blood (UCB) donor.
  * Myelodysplastic syndromes (MDS)
  * Juvenile myelomonocytic leukemia (JMML)
  * Chronic myeloid leukemia (CML), with detectable disease by polymerase chain reaction (PCR)
* Patients must have a suitable donor based on the University of California, San Francisco (UCSF) Pediatric Bone Marrow Transplant (BMT) standard operating procedures (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 (aspartate aminotransferase (AST)/alanine aminotransferase (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, glomerular filtration rate (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 Pulmonary function testing(PFTs), then no active lung disease by chest x-ray (CXR) and/or oxygen (O2) Saturation ≥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

Primary outcomes:
measure: Number of Participants With Treatment-Related Adverse Events as a Measure of Safety and Tolerability
timeFrame: Up to 5 years on average
Secondary outcomes:
measure: Engraftment Rate of Patients With Non-malignant Diseases (Stratum A)
timeFrame: 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.
measure: Mixed-donor Chimerism Rate of Patients With High-risk Myeloid Malignancies (Stratum B)
timeFrame: Participants will have peripheral blood chimerism assessed at Day 100 post hematopoietic stem cell transplant and then monthly until stable.
measure: Serum Concentrations and Potential for Drug-drug Interaction of Fludarabine and Clofarabine
timeFrame: Pharmacokinetics (PK) blood sampling Days -5 to -2 pre-hematopoietic stem cell transplant.
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Christopher C Dvorak, MD
role: PRINCIPAL_INVESTIGATOR
References: