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

NCT ID: NCT01596699

Last Updated: 2020-02-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-05-24
• Study Completion Date: 2019-06-30

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.

Conditions

Myeloid Malignancy; Bone Marrow Failure Syndrome; Transfusion-dependent Red Blood Cell (RBC) Defect; Congenital Immunodeficiency; Metabolic Disease; Severe Immune Dysregulation

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Patients with Myeloid Malignancies

Group Type: EXPERIMENTAL

Busulfan

Intervention Type: DRUG

0.8 mg/kg/dose q6hrs or 1.1 mg/kg/dose q6hrs, IV, Day -9 to Day -6 pre-HCT

Fludarabine

Intervention Type: DRUG

40 mg/m2 or 1.33 mg/kg, IV, Day -5 to Day -2 pre-HCT

Clofarabine

Intervention Type: DRUG

10 mg/m2 or 0.33 mg/kg, IV, Day -5 to Day -2 pre-HCT

Patients with Non-Malignancies

Group Type: EXPERIMENTAL

Alemtuzumab

Intervention Type: DRUG

0.5 mg/kg (max 15 mg or max 6 mg), IV, Day -12 to Day -10 pre-HCT

Busulfan

Intervention Type: DRUG

0.8 mg/kg/dose q6hrs or 1.1 mg/kg/dose q6hrs, IV, Day -9 to Day -6 pre-HCT

Fludarabine

Intervention Type: DRUG

40 mg/m2 or 1.33 mg/kg, IV, Day -5 to Day -2 pre-HCT

Clofarabine

Intervention Type: DRUG

10 mg/m2 or 0.33 mg/kg, IV, Day -5 to Day -2 pre-HCT

Interventions

Alemtuzumab

0.5 mg/kg (max 15 mg or max 6 mg), IV, Day -12 to Day -10 pre-HCT

Intervention Type: DRUG

Busulfan

0.8 mg/kg/dose q6hrs or 1.1 mg/kg/dose q6hrs, IV, Day -9 to Day -6 pre-HCT

Intervention Type: DRUG

Fludarabine

40 mg/m2 or 1.33 mg/kg, IV, Day -5 to Day -2 pre-HCT

Intervention Type: DRUG

Clofarabine

10 mg/m2 or 0.33 mg/kg, IV, Day -5 to Day -2 pre-HCT

Intervention Type: DRUG

Other Intervention Names

Campath; Busulfex; Fludara; Clolar

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

• Minimum Eligible Age: 3 Months
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christopher C Dvorak, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

University of California, San Francisco

San Francisco, California, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form: Minor-Parental

View Document

Document Type: Informed Consent Form: Assent (Ages 7-12)

View Document

Document Type: Informed Consent Form: Adult Adolescent

View Document

Other Identifiers

NCI-2012-00800

Identifier Type: REGISTRY

Identifier Source: secondary_id

110819

Identifier Type: -

Identifier Source: org_study_id