Myeloid MalignancyPhase 2NCT01596699
Pilot Trial of Clofarabine Added to Standard Busulfan and Fludarabine for Conditioning Prior to Allogeneic Hematopoietic Cell Transplantation
A Phase 2 study testing Alemtuzumab, Busulfan and Fludarabine in people with Myeloid Malignancy and Bone Marrow Failure Syndrome, run by University of California, San Francisco at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 months to 30 years
- Conditions the study is for
- Myeloid Malignancy, Bone Marrow Failure Syndrome, Transfusion-dependent Red Blood Cell (RBC) Defect
- What is being tested?
- Alemtuzumab, Busulfan and Fludarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 24 May 2012to Jun 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 months to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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)
Show all 18Show fewer
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Francisco
San Francisco, California, 94143
About this study
Official title: 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.
- Conditions
- Myeloid Malignancy, Bone Marrow Failure Syndrome, Transfusion-dependent Red Blood Cell (RBC) Defect, Congenital Immunodeficiency, Metabolic Disease, Severe Immune Dysregulation
- Being tested
- Alemtuzumab, Busulfan, Fludarabine, Clofarabine
- Keywords
- conditioning, allogeneic, hematopoietic, cell, transplantation, HCT
- Medical subject headings
- Bone Marrow Failure Disorders, Metabolic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlemtuzumabDrug
Also called Campath
0.5 mg/kg (max 15 mg or max 6 mg), IV, Day -12 to Day -10 pre-HCT
BusulfanDrug
Also called Busulfex
0.8 mg/kg/dose q6hrs or 1.1 mg/kg/dose q6hrs, IV, Day -9 to Day -6 pre-HCT
FludarabineDrug
Also called Fludara
40 mg/m2 or 1.33 mg/kg, IV, Day -5 to Day -2 pre-HCT
ClofarabineDrug
Also called Clolar
10 mg/m2 or 0.33 mg/kg, IV, Day -5 to Day -2 pre-HCT
| Study group | Role | What they receive |
|---|---|---|
| Patients with Myeloid Malignancies | Experimental | Not described Receives: Drug: Busulfan; Drug: Fludarabine; Drug: Clofarabine |
| Patients with Non-Malignancies | Experimental | Not described Receives: Drug: Alemtuzumab; Drug: Busulfan; Drug: Fludarabine; Drug: Clofarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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%.
Measured: Up to 5 years on average
Secondary outcomes (3)
Engraftment Rate of Patients With Non-malignant Diseases (Stratum A)
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.
Measured: 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)
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.
Measured: 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
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
Measured: Pharmacokinetics (PK) blood sampling Days -5 to -2 pre-hematopoietic stem cell transplant.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2012 (estimated)
- Study start24 May 2012
- Primary completionJun 2019
- Study completionJun 2019
Why it stopped: Triggering of futility rule; Interim analysis suggested no statistical superiority over historic controls
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Myeloid MalignancyStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Christopher C Dvorak, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01596699
- Sponsor's protocol ID
- 110819
- Other IDs
- NCI-2012-00800
- Status last verified
- Feb 2020
- First submitted
- 7 May 2012
- Last updated
- 26 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Trial of Clofarabine Added to Standard Busulfan and Fludarabine for Conditioning Prior to Allogeneic Hematopoietic Cell Transplantation
- ClinicalTrials.gov ID
- NCT01596699
- Acronym / sponsor ID
- 110819
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Triggering of futility rule; Interim analysis suggested no statistical superiority over historic controls
- Enrolment
- 16 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Study start
- 24 May 2012 (actual)
- Primary completion
- Jun 2019 (actual)
- Study completion
- Jun 2019 (actual)
- First posted
- 11 May 2012 (estimated)
- Results
- Posted 26 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients with Myeloid Malignancies | Experimental | Drug: Busulfan, Drug: Fludarabine, Drug: Clofarabine |
| Patients with Non-Malignancies | Experimental | Drug: Alemtuzumab, Drug: Busulfan, Drug: Fludarabine, Drug: Clofarabine |
Who may qualify
- Ages
- 3 months to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (18 listed)
- Patients must be ≥ 3 months and ≤30 years of age.
- Stratum A: Non-Malignant Diseases, including:
- Stratum B: Myeloid Malignancies, including:
- 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.
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlemtuzumabAlso: Campath0.5 mg/kg (max 15 mg or max 6 mg), IV, Day -12 to Day -10 pre-HCT | Drug | Patients with Non-Malignancies |
| BusulfanAlso: Busulfex0.8 mg/kg/dose q6hrs or 1.1 mg/kg/dose q6hrs, IV, Day -9 to Day -6 pre-HCT | Drug | Patients with Myeloid Malignancies, Patients with Non-Malignancies |
| FludarabineAlso: Fludara40 mg/m2 or 1.33 mg/kg, IV, Day -5 to Day -2 pre-HCT | Drug | Patients with Myeloid Malignancies, Patients with Non-Malignancies |
| ClofarabineAlso: Clolar10 mg/m2 or 0.33 mg/kg, IV, Day -5 to Day -2 pre-HCT | Drug | Patients with Myeloid Malignancies, Patients with Non-Malignancies |
Primary outcome
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%.
3 secondary outcomes
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.
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.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christopher C Dvorak, MD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Alemtuzumab, Busulfan and Fludarabine in people with Myeloid Malignancy and Bone Marrow Failure Syndrome, run by University of California, San Francisco at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-Related Adverse Events as a Measure of Safety and Tolerability (time frame: Up to 5 years on average). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Feb 2020.