Acute Myeloblastic LeukemiaPhase 2CloBu4NCT01457885
Multi-center Study of Myeloablative Allo Stem Cell Transplant for Non-remission AML Using CloBu4 Regimen
A Phase 2 study testing Clofarabine/Busulfan x 4 and Peripheral blood stem cell transplant in people with Acute Myeloblastic Leukemia, run by University of Michigan Rogel Cancer Center at 12 sites in 2 countries.
Trial summary
Although transplant results for AML in complete remission (CR) at the time of transplant have improved, transplant results for non-remission AML have been quite poor. Most multi-center studies have focused on standard risk AML patients and not many studies have been done in this population of patients with… Read more about this study
- Who is it for?
- Ages 2 to 65 years
- Conditions the study is for
- Acute Myeloblastic Leukemia
- What is being tested?
- Clofarabine/Busulfan x 4 and Peripheral blood stem cell transplant
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- 12 sitesin 2 countries
- Study dates
- Nov 2011to 14 Jun 2016
- 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 2 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Disease Criteria
- AML not in remission at the time of transplant
- "Not in remission" is defined as "greater than 5.0% bone marrow blasts by aspirate morphology," as determined by a bone marrow aspirate obtained within 2 weeks of study registration.
- For primary induction failure patients: Patients must have failed at least 2 induction regimens.
- For patients with relapsed disease: Patients who relapse more than 6 months after preceding remission must fail at least one reinduction regimen to be eligible. For patients in whom the preceding remission is equal to or shorter than 6 months duration, no re-induction regimen is required to qualify for this protocol.
- If the pre-transplant bone marrow aspirate and biopsy are hypoplastic (less than 10% cellularity), and blast percentages cannot be determined, the patient is eligible if the preceding bone marrow met the above criteria.
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- Patients with peripheral circulating blasts or patients with extramedullary leukemia are eligible if bone marrow aspirate and biopsy meets the above criteria. Age and Organ Function Criteria
- Age: 2 to 65 years in age.
- Cardiac: LVEF ≥ 40% by MUGA (Multi Gated Acquisition) scan or echocardiogram.
- Pulmonary: FEV1 and FVC capacity) ≥ 40% predicted, DLCO (corrected for hemoglobin) ≥ 40% of predicted.
- Children who are unable to cooperate for pulmonary function tests (PFTs), must have no evidence of dyspnea at rest, no exercise intolerance, and not require supplemental oxygen therapy.
- Renal: Age equal to or older than 12: The estimated creatinine clearance (CrCl) must be equal or greater than 60 mL/min/1.73 m2 as calculated by the Cockcroft-Gault Formula. Age younger than 12: Either estimated or measured CrCl should be greater than 90 ml/min/1.73m2. For estimation, Schwartz formula will be used.
- Hepatic: Serum bilirubin ≤ 1.5 x upper limit of normal (ULN); (AST)/ ALT ≤ 2.5 x ULN; Alkaline phosphatase ≤ 2.5 x ULN
- Performance status: Karnofsky ≥ 70%., or Lansky≥70% Consent: All patients must sign informed consent
Who cannot join
- Active life-threatening cancer requiring treatment other than AML
- Non-compliant to medications.
- No appropriate caregivers identified.
- HIV1 (Human Immunodeficiency Virus-1) or HIV2 positive
- Active life-threatening cancer requiring treatment other than AML
- Uncontrolled medical or psychiatric disorders.
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- Uncontrolled infections, defined as positive blood cultures within 72 hours of study entry, or evidence of progressive infection
- Active central nervous system (CNS) leukemia
- Preceding allogeneic HSCT
- Receiving intensive chemotherapy within 21 days of registration.
- Patients with preceding primary myelofibrosis
- Peripheral blasts > 10,000/μL at the time of registration
Trial locations and contacts
12 sites in 2 countries.
12 sites in 2 countries
United States10 sites
University of Michigan Cancer Center
Ann Arbor, Michigan, 48109
University of Alabama, Birmingham
Birmingham, Alabama, 35233
City of Hope National Medical Center
Duarte, California, 91010
Hackensack University Medical Center
Hackensack, New Jersey, 07601
University of Kansas Medical Center
Kansas City, Kansas, 66160
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Vanderbuilt University
Nashville, Tennessee, 37232
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
University of Washington
Seattle, Washington, 98109
Washington University at St Louis
St Louis, Missouri, 63110
Canada2 sites
Hospital for Sick Children
Toronto, Ontario, M5G 1X8
Princess Margaret Hospital
Toronto, Ontario, M5G 2M9
About this study
Official title: Multi-center Single Arm Phase II Study of Myeloablative Allogeneic Stem Cell Transplantation for Non-remission Acute Myeloblastic Leukemia (AML) Using Clofarabine and Busulfan x 4 (CloBu4) Regimen
Although transplant results for AML in complete remission (CR) at the time of transplant have improved, transplant results for non-remission AML have been quite poor. Most multi-center studies have focused on standard risk AML patients and not many studies have been done in this population of patients with non-remission AML. There are a large number of older patients with non-remission AML because the complete remission rate with induction chemotherapy decreases with age. Such older patients do not tolerate conventional full intensity conditioning regimens. Thus, an effective and tolerable conditioning regimen for non-remission AML is a great unmet need for current transplant practice.
From the investigators earlier study, it is suggested that replacing Fludarabine of standard FluBu4 regimen by Clofarabine (a related drug with much more potent anti-leukemia effect) in the transplant conditioning regimen may potentiate the anti-tumor activity of the conditioning regimen without adding significant toxicity, a goal of new conditioning regimen development.
The investigators expect to enroll a total of 75 patients from about fifteen sites. The investigators main objective is to confirm both the safety and efficacy as measured by one-year overall survival, of the CloBu4 combination as full intensity conditioning for non-remission acute myelogenous leukemia.
- Conditions
- Acute Myeloblastic Leukemia
- Being tested
- Clofarabine/Busulfan x 4, Peripheral blood stem cell transplant
- Keywords
- AML
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Clofarabine/Busulfan x 4Drug
- Clofarabine IV dose level: 40 mg/m2/day x 5 days
- Busulfan IV dose level: 3.2 mg/kg daily x 4 days
Peripheral blood stem cell transplantProcedure or surgery
Peripheral blood stem cell transplant, after pre-conditioning drug treatment
| Study group | Role | What they receive |
|---|---|---|
| CloBu4 regimen | Experimental | After pre-conditioning with CloBu4 (Clofarabine/Busulfan x 4), subjects will receive a peripheral blood stem cell transplant Receives: Drug: Clofarabine/Busulfan x 4; Procedure: Peripheral blood stem cell transplant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative Incidence of Non Relapse Mortality (NRM)
Percentage of patients passed without relapse/recurrence at 1 year.
Measured: 1 year
Secondary outcomes (2)
The Percentage of Patients Alive at 1 Year
Overall survival was calculated following transplant using a CloBu4 conditioning regimen for patients with non-remission AML
Measured: 1 year
Incidence of Relapse
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2011 (estimated)
- Study startNov 2011
- Primary completionNov 2014
- Study completion14 Jun 2016
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 Acute Myeloblastic LeukemiaStudies of the same condition, open and under way.
- More trials run by University of Michigan Rogel Cancer CenterThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Genzyme, a Sanofi Company, Otsuka Pharmaceutical Development & Commercialization, Inc.
- Responsible party
- Sponsor
- Investigators
- Shin Mineishi, MD, Study chair, University of Alabama at BirminghamJohn M Magenau, MD, Principal investigator, University of Michigan, Department of Internal MedicineStephen J Forman, MD, Study chair, City of Hope National Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01457885
- Sponsor's protocol ID
- UMCC 2011.038
- Acronym
- CloBu4
- Status last verified
- May 2017
- First submitted
- 19 Oct 2011
- Last updated
- 2 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi-center Single Arm Phase II Study of Myeloablative Allogeneic Stem Cell Transplantation for Non-remission Acute Myeloblastic Leukemia (AML) Using Clofarabine and Busulfan x 4 (CloBu4) Regimen
- ClinicalTrials.gov ID
- NCT01457885
- Acronym / sponsor ID
- CloBu4 / UMCC 2011.038
- Conditions
- Acute Myeloblastic Leukemia
- Keywords
- AML
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- University of Michigan Rogel Cancer CenterUniversity, hospital or other
- Collaborators
- Genzyme, a Sanofi Company, Otsuka Pharmaceutical Development & Commercialization, Inc.
- Study start
- Nov 2011
- Primary completion
- Nov 2014 (actual)
- Study completion
- 14 Jun 2016 (actual)
- First posted
- 24 Oct 2011 (estimated)
- Results
- Posted 25 Jul 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Although transplant results for AML in complete remission (CR) at the time of transplant have improved, transplant results for non-remission AML have been quite poor. Most multi-center studies have focused on standard risk AML patients and not many studies have been done in this population of patients with non-remission AML. There are a large number of older patients with non-remission AML because the complete remission rate with induction chemotherapy decreases with age. Such older patients do not tolerate conventional full intensity conditioning regimens. Thus, an effective and tolerable conditioning regimen for non-remission AML is a great unmet need for current transplant practice.
From the investigators earlier study, it is suggested that replacing Fludarabine of standard FluBu4 regimen by Clofarabine (a related drug with much more potent anti-leukemia effect) in the transplant conditioning regimen may potentiate the anti-tumor activity of the conditioning regimen without adding significant toxicity, a goal of new conditioning regimen development.
The investigators expect to enroll a total of 75 patients from about fifteen sites. The investigators main objective is to confirm both the safety and efficacy as measured by one-year overall survival, of the CloBu4 combination as full intensity conditioning for non-remission acute myelogenous leukemia.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CloBu4 regimen | Experimental | Drug: Clofarabine/Busulfan x 4, Procedure: Peripheral blood stem cell transplantAfter pre-conditioning with CloBu4 (Clofarabine/Busulfan x 4), subjects will receive a peripheral blood stem cell transplant |
Who may qualify
- Ages
- 2 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (14 listed)
- Disease Criteria
- AML not in remission at the time of transplant
- If the pre-transplant bone marrow aspirate and biopsy are hypoplastic (less than 10% cellularity), and blast percentages cannot be determined, the patient is eligible if the preceding bone marrow met the above criteria.
- Patients with peripheral circulating blasts or patients with extramedullary leukemia are eligible if bone marrow aspirate and biopsy meets the above criteria. Age and Organ Function Criteria
- Age: 2 to 65 years in age.
Key exclusion criteria (12 listed)
- Active life-threatening cancer requiring treatment other than AML
- Non-compliant to medications.
- No appropriate caregivers identified.
- HIV1 (Human Immunodeficiency Virus-1) or HIV2 positive
- Active life-threatening cancer requiring treatment other than AML
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 |
|---|---|---|
| Clofarabine/Busulfan x 4* Clofarabine IV dose level: 40 mg/m2/day x 5 days * Busulfan IV dose level: 3.2 mg/kg daily x 4 days | Drug | CloBu4 regimen |
| Peripheral blood stem cell transplantPeripheral blood stem cell transplant, after pre-conditioning drug treatment | Procedure or surgery | CloBu4 regimen |
Primary outcome
Cumulative Incidence of Non Relapse Mortality (NRM)
Time frame: 1 year
Percentage of patients passed without relapse/recurrence at 1 year.
2 secondary outcomes
The Percentage of Patients Alive at 1 Year
Time frame: 1 year
Incidence of Relapse
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Shin Mineishi, MD study chair
University of Alabama at Birmingham
John M Magenau, MD principal investigator
University of Michigan, Department of Internal Medicine
Stephen J Forman, MD study chair
City of Hope National Medical Center
12 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Clofarabine/Busulfan x 4 and Peripheral blood stem cell transplant in people with Acute Myeloblastic Leukemia, run by University of Michigan Rogel Cancer Center at 12 sites in 2 countries.
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 14 inclusion and 12 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: finished, as of the sponsor's last update on 2 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, Canada. 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 25 Jul 2016). 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?
Cumulative Incidence of Non Relapse Mortality (NRM) (time frame: 1 year). 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 2 Jun 2017.