- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01596699
Pilot Trial of Clofarabine Added to Standard Busulfan and Fludarabine for Conditioning Prior to Allogeneic Hematopoietic Cell Transplantation
February 25, 2020 updated by: University of California, San Francisco
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.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
16
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
California
-
San Francisco, California, United States, 94143
- University of California, San Francisco
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
3 months to 30 years (Child, Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Patients with Myeloid Malignancies
|
0.8 mg/kg/dose q6hrs or 1.1 mg/kg/dose q6hrs, IV, Day -9 to Day -6 pre-HCT
Other Names:
40 mg/m2 or 1.33 mg/kg, IV, Day -5 to Day -2 pre-HCT
Other Names:
10 mg/m2 or 0.33 mg/kg, IV, Day -5 to Day -2 pre-HCT
Other Names:
|
Experimental: Patients with Non-Malignancies
|
0.8 mg/kg/dose q6hrs or 1.1 mg/kg/dose q6hrs, IV, Day -9 to Day -6 pre-HCT
Other Names:
40 mg/m2 or 1.33 mg/kg, IV, Day -5 to Day -2 pre-HCT
Other Names:
10 mg/m2 or 0.33 mg/kg, IV, Day -5 to Day -2 pre-HCT
Other Names:
0.5 mg/kg (max 15 mg or max 6 mg), IV, Day -12 to Day -10 pre-HCT
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Treatment-Related Adverse Events as a Measure of Safety and Tolerability
Time Frame: Up to 5 years on average
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Engraftment Rate of Patients With Non-malignant Diseases (Stratum A)
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.
|
Engraftment will be defined as the development of an Absolute Neutrophil Count (ANC) >500 for 3 consecutive days plus donor CD14/15 cells >70%.
The engraftment rate in the population used for historical control is 40%.
If 3 patients in Stratum A experience graft rejection, this stratum will close early for failing to achieve superior engraftment compared to standard-of-care.
|
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)
Time Frame: Participants will have peripheral blood chimerism assessed at Day 100 post hematopoietic stem cell transplant and then monthly until stable.
|
Full-donor chimerism will be defined by as ≥99% donor cells by Short Tandem Repeat (STR) analysis in all cell lines (CD3, CD14/15, and CD19) in peripheral blood.
The historic control for Stratum B was determined using the 20 patients who were transplanted from 2005 - 2010 with Busulfan (BU)-based regimens and who retrospectively would have been eligible for the current trial.
Of these 20 patients, at 100 days post-HCT, only 8 (40%) patients had full-donor chimerism.
If 5 patients in Stratum B experienced mixed-donor chimerism at Day 100, we will close this stratum early for failing to achieve superior donor cell engraftment compared to standard-of-care.
|
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
Time Frame: Pharmacokinetics (PK) blood sampling Days -5 to -2 pre-hematopoietic stem cell transplant.
|
Fludarabine and clofarabine drug levels and potential covariates influencing drug exposure such as renal function and genetic variants involved in drug metabolism, distribution, and activation will be analyzed using standard population pharmacokinetic methods using non-linear mixed effects modeling (NONMEM) software
|
Pharmacokinetics (PK) blood sampling Days -5 to -2 pre-hematopoietic stem cell transplant.
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Christopher C Dvorak, MD, University of California, San Francisco
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
May 24, 2012
Primary Completion (Actual)
June 1, 2019
Study Completion (Actual)
June 1, 2019
Study Registration Dates
First Submitted
May 7, 2012
First Submitted That Met QC Criteria
May 9, 2012
First Posted (Estimate)
May 11, 2012
Study Record Updates
Last Update Posted (Actual)
February 26, 2020
Last Update Submitted That Met QC Criteria
February 25, 2020
Last Verified
February 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Bone Marrow Diseases
- Hematologic Diseases
- Metabolic Diseases
- Bone Marrow Failure Disorders
- Pancytopenia
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Immunological
- Clofarabine
- Fludarabine
- Busulfan
- Alemtuzumab
Other Study ID Numbers
- 110819
- NCI-2012-00800 (Registry Identifier: NCI Clinical Trials Reporting Program (CTRP))
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Myeloid Malignancy
-
Henry Ford Health SystemRecruitingMyeloid MalignancyUnited States
-
Aprea TherapeuticsCompletedMyeloid MalignancyUnited States
-
Benjamin TomlinsonNot yet recruitingAcute Myeloid Leukemia | Myeloid MalignancyUnited States
-
Shanghai General Hospital, Shanghai Jiao Tong University...RecruitingMyeloid Malignancy | Venetoclax | Hypomethylating AgentChina
-
Ruijin HospitalRecruitingP53 Mutation | Myeloid Malignancy | MDS | AmlChina
-
Bien-Willner Physicians Group PANo One Left Alone; Carolina Blood and Cancer Care AssociatesNot yet recruitingAdvanced Cancer | Myeloid Malignancy | Solid Tumor, AdultUnited States
-
Ascentage Pharma Group Inc.Suzhou Yasheng Pharmaceutical Co., Ltd.RecruitingMyeloid Malignancy | Relapsed/Refractory Acute Myeloid LeukaemiaChina
-
Xianmin Song, MDRecruitingLeukemia, Myeloid, Acute | Myeloid Malignancy | MDS | Hematopoietic Stem Cell TransplantationChina
-
Kartos Therapeutics, Inc.CompletedAcute Myeloid Leukemia | Cancer | Oncology | Advanced Malignancy | Oncology PatientsUnited States
-
Gilead SciencesTerminatedAcute Myeloid Leukemia | Hematologic MalignancyJapan
Clinical Trials on Busulfan
-
Hospital Israelita Albert EinsteinUnknownAcute Leukemia | Immunodeficiency | Chronic Leukemia | Lymphoproliferative Disease | Myeloproliferative DiseaseBrazil
-
Institut Paoli-CalmettesUnknownAcute Myeloid Leukemia | Myelodysplastic SyndromeFrance
-
Shanghai Public Health Clinical CenterR&D Kanglin BiotechUnknownHIV Infections | AIDSChina
-
City of Hope Medical CenterSangamo Therapeutics; California Institute for Regenerative Medicine (CIRM)Active, not recruiting
-
Pediatric Brain Tumor ConsortiumNational Cancer Institute (NCI)CompletedSarcoma | Lymphoma | Leukemia | Brain and Central Nervous System Tumors | Metastatic Cancer | Retinoblastoma | Childhood Germ Cell TumorUnited States
-
Baylor Research InstituteGenzyme, a Sanofi CompanyCompletedLeukemia | Myelodysplastic SyndromeUnited States
-
Duke UniversityNational Cancer Institute (NCI)CompletedBrain and Central Nervous System TumorsUnited States
-
Alberta Health servicesUnknownHematologic MalignancyCanada
-
Institut Paoli-CalmettesNot yet recruitingAcute Leukemia | Myeloproliferative Neoplasm | Mielodysplasic Syndrome
-
University of ArizonaCompletedHematologic Neoplasms | Multiple Myeloma | Myelofibrosis | Anemia, Aplastic | Hemoglobinuria, ParoxysmalUnited States