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

NCT01596699 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 110819NCI-2012-00800
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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

Keywords

conditioning; allogeneic; hematopoietic; cell; transplantation; HCT

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-Related Adverse Events as a Measure of Safety and Tolerability

  Severe Toxicity will be defined as death or Grade IV by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 pulmonary or hepatic failure (including moderate veno-occlusive disease(VOD) related to the transplant conditioning regimen within 100 days post-HCT. VOD will be defined by standard criteria. Patients must have Bilirubin \>2.0 plus Hepatomegaly and/or Right upper quadrant (RUQ) pain plus Weight gain \>5%.

  Up to 5 years on average

Secondary Outcomes (3)

• Engraftment Rate of Patients With Non-malignant Diseases (Stratum A)

  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.

• Mixed-donor Chimerism Rate of Patients With High-risk Myeloid Malignancies (Stratum B)

  Participants will have peripheral blood chimerism assessed at Day 100 post hematopoietic stem cell transplant and then monthly until stable.

• Serum Concentrations and Potential for Drug-drug Interaction of Fludarabine and Clofarabine

  Pharmacokinetics (PK) blood sampling Days -5 to -2 pre-hematopoietic stem cell transplant.

Study Arms (2)

Patients with Myeloid Malignancies

EXPERIMENTAL

Drug: Busulfan; Drug: Fludarabine; Drug: Clofarabine

Patients with Non-Malignancies

EXPERIMENTAL

Drug: Alemtuzumab; Drug: Busulfan; Drug: Fludarabine; Drug: Clofarabine

Interventions

Alemtuzumab DRUG

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

Also known as: Campath

Patients with Non-Malignancies

Busulfan DRUG

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

Also known as: Busulfex

Patients with Myeloid Malignancies; Patients with Non-Malignancies

Fludarabine DRUG

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

Also known as: Fludara

Patients with Myeloid Malignancies; Patients with Non-Malignancies

Clofarabine DRUG

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

Also known as: Clolar

Patients with Myeloid Malignancies; Patients with Non-Malignancies

Eligibility Criteria

• Age: 3 Months - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Bone Marrow Failure Disorders; Metabolic Diseases

Interventions

Alemtuzumab; Busulfan; fludarabine; fludarabine phosphate; Clofarabine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides

Limitations and Caveats

Study closed prior to completion. Interim analysis suggested treatments would not demonstrate statistical superiority over historic controls.

Results Point of Contact

• Title: Dr. Christopher Dvorak, MD
• Organization: University of California, San Francisco

Christopher.Dvorak@ucsf.edu

(415) 476-0554

Study Officials

• Christopher C Dvorak, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2012
• First Posted: May 11, 2012
• Study Start: May 24, 2012
• Primary Completion: June 1, 2019
• Study Completion: June 1, 2019
• Last Updated: February 26, 2020
• Results First Posted: February 26, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)