Acute Myeloid LeukemiaPhase 2NCT01643668
Busulfan/Clofarabine + Allogeneic Stem Cell Transplantation
A Phase 2 study testing Busulfan, Clofarabine and Allogeneic Stem Cell Infusion in people with Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia, run by Massachusetts General Hospital at 3 sites in United States.
Trial summary
This research is a phase II clinical trial. Phase II clinical trials test the effectiveness of an investigational intervention to learn whether it works in treating a specific cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndrome
- What is being tested?
- Busulfan, Clofarabine and Allogeneic Stem Cell Infusion
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 3 sitesUnited States
- Study dates
- Jul 2012to Aug 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Must have well-matched adult donor willing to donate peripheral blood stem cells with well-matched defined as 8/8 matched related or unrelated donor
- Adequate organ functioning
Who cannot join
- Pregnant or breastfeeding
- Psychiatric disease severely impairing the compliance of the patient to participate in the study and/or give informed consent
- Evidence of prior exposure to HIV or HCV
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
About this study
Official title: Phase II Study of Reduced Intensity Conditioning With Busulfan/Clofarabine Followed by Allogeneic Stem Cell Transplantation
This research is a phase II clinical trial. Phase II clinical trials test the effectiveness of an investigational intervention to learn whether it works in treating a specific cancer. "Investigational" means that the study intervention is still being studied and that research doctors are trying to find out more about it. It also means that the FDA has not yet approved this study intervention for your type of cancer.
All participants on this study are treated in an identical manner. The investigators are doing this study because there continues to be a significant risk of relapse of disease after reduced intensity transplantation. In studies which have compared transplants using high-doses of chemotherapy and/or radiation versus reduced intensity transplants, patients undergoing reduced intensity transplants appear to have higher rates of relapse, but lower rates of toxicity and complication. This study attempts to utilize clofarabine, a newer chemotherapy agent shown to be quite active in AML, ALL, and MDS, to increase the anti-tumor effects of the conditioning regimen without accumulating unacceptable toxicity.
Read more
The reduced intensity allogeneic stem cell transplantation procedure involves giving you chemotherapy in relatively less intense doses to suppress your immune system. This is followed by an infusion of healthy blood stem cells from a matched related donor or a matched unrelated volunteer donor. It is hoped that these donor cells can eventually then attack any cancer cells which remain.
In this research study, the investigators are looking to see how well this new combination of busulfan and clofarabine works in reduced intensity allogeneic stem cell transplantation. By "works" the investigators mean to analyze safety, ability of donor cells to engraft (take hold), as well as measures of complications including toxicity, infections, graft-vs-host disease (GVHD), and relapse.
Read the detailed description
You will start the conditioning regimen, which is also called the preparative regimen. Conditioning is done to kill more cancer cells which may remain as well as prepare your body for transplant. You will receive the conditioning drugs into a vein. The conditioning regimen consists of the following drugs: Busulfan and Clofarabine.
While you are in the hospital you will have regular physical exams and you will be asked specific questions about any problems that you might be having. You will also have blood tests every day to look at how your bone marrow is recovering, to give possible transfusional support, and how to see how your liver and kidneys are functioning.
You will receive the following drugs before and after the allogeneic stem cell transplant: Neupogen (G-CSF) injections, drugs to prevent infections, Tacrolimus to prevent GVHD and Methotrexate.
You will have routine and regular follow-up in the transplant clinic after discharge from the hospital. The following will be performed at each visit:
Physical exam to monitor your health and check for signs of GVHD, infections and any side effects you may be having; Blood draw for routine blood tests to measure your blood cell count and chemistry; Blood tests to see if the transplanted stem cells are being accepted and are growing in the body (engraftment); Bone marrow biopsy to see the status of the underlying disease (to be done around 100 days after the stem cell transplant).
You will be asked to return to the clinic, at a minimum, for follow-up visits at 6 months, 9 months, 12 months, 18 months and 24 months after your stem cell transplant.
- Being tested
- Busulfan, Clofarabine, Allogeneic Stem Cell Infusion
- Medical subject headings
- Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BusulfanDrug
Busulfan as part of reduced intensity conditioning prior to allogeneic stem cell transplantation
ClofarabineDrug
Clofarabine as part of reduced intensity conditioning prior to allogeneic stem cell transplantation
Allogeneic Stem Cell InfusionProcedure or surgery
Allogeneic stem cell transplantation after reduced intensity conditioning with busulfan / clofarabine chemotherapy
| Study group | Role | What they receive |
|---|---|---|
| BuClo RIC + SCT | Experimental | Busulfan and Clofarabine (BuClo) reduced intensity conditioning (RIC) followed by allogeneic stem cell Transplantation (SCT) Receives: Drug: Busulfan; Drug: Clofarabine; Procedure: Allogeneic Stem Cell Infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of Donor Stem Cell Engraftment: ANC Count
Patients are considered to have achieved donor cell engraftment if they have an absolute neutrophil count (ANC) of at least 500 cells/uL of blood for 3 consecutive measurements and at least 75% of hematopoietic elements are donor-derived as determined by chimerism assays from peripheral blood prior to day +40 after Busulfan/Clofarabine (BuClo) reduced intensity allogeneic stem cell transplantation
Measured: 1, 2, 3, and 4 weeks after transplantation
Donor Stem Cell Engraftment: Platelet Count
Platelet recovery was defined as having a platelet count of at least 20,000 platelets/uL of blood on 2 consecutive measurements without transfusional support prior to day +100 after BuClo RIC HSCT.
Measured: 1, 2, 3, 4, 8, and 14 weeks post transplant
Secondary outcomes (7)
Cumulative Incidence of Non-relapse Mortality
The percentage of participants that experienced non-relapse mortality (NRM) at day 100 and 1 year after BuClo RIC SCT. Non-relapse mortality is any mortality that is not associated with or proceeded by disease progression of prior cancers.
Measured: 100 days, 1 year
Progression-Free and Overall Survival
The 1-year and 2-year progression-free and overall survival measured from the time of stem cell transplantation. Progression is the recurrence or increase in the number of cancer cells found in the body.
Measured: 1 year, 2 years
Cumulative Incidence and Severity of Acute GVHD Within 100 Days Post Transplant
The percentage of participants who experienced grades 2-4 and grades 3-4 acute graft-versus-host disease (GVHD) by 100 days post transplantation. GVHD is a condition that can occur following an allogenic stem cell transplantation when the donated bone marrow or peripheral stem cells view the recipients body as foreign and the donated cell/marrow attack the body. Acute GVHD is generally observed within the first 100 days post transplant. Acute GVHD is associated with increased treatment related morbidity and mortality. Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening. The grade of the GVHD is determined by grading GHVD associated adverse events. Associated adverse events were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4 which uses the same mild, moderate, severe, life threatening grading system as the overall GHVD assessment.
Measured: 100 days
Cumulative Incidence of Chronic GVHD at One Year
The percentage of participants who experienced chronic Graft Versus Host Disease (GVHD) by one year. GVHD is a condition that can occur following an allogenic stem cell transplantation when the donated bone marrow or peripheral stem cells view the recipients body as foreign and the donated cell/marrow attack the body. Chronic GVHD normally occurs after the first 100 days post transplantation. Chronic GVHD can adversely influence long term survival.
Measured: 1 year
Incidence of Hepatic Veno-occlusive Disease
The number of participants that experienced hepatic veno-occlusive disease (VOD). VOD is a condition in which some of the small veins in the liver are obstructed.
Measured: 2 years
Grade 3 or 4 Toxicities
The number of participants that experienced the specified grade 3 and 4 non-hematological toxicities during treatment and follow-up as assessed by Common Terminology Criteria for Adverse Events version 4(CTAE v 4.0). Grade 3 toxicity is considered to be severe and grade 4 is considered to be life threatening.
Measured: 2 years
Infection-related Complications
The number of patients with infection-related complications
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 posted18 Jul 2012 (estimated)
- Study startJul 2012
- Primary completionAug 2016
- Study completionAug 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 Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe 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
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yi-Bin A. Chen, MD, Massachusetts General Hospital
- Investigators
- Yi-Bin Chen, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01643668
- Sponsor's protocol ID
- 12-128
- Status last verified
- Jun 2017
- First submitted
- 12 Jun 2012
- Last updated
- 13 Jul 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 13 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Reduced Intensity Conditioning With Busulfan/Clofarabine Followed by Allogeneic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT01643668
- Acronym / sponsor ID
- 12-128
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- Jul 2012
- Primary completion
- Aug 2016 (actual)
- Study completion
- Aug 2016 (actual)
- First posted
- 18 Jul 2012 (estimated)
- Results
- Posted 13 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research is a phase II clinical trial. Phase II clinical trials test the effectiveness of an investigational intervention to learn whether it works in treating a specific cancer. "Investigational" means that the study intervention is still being studied and that research doctors are trying to find out more about it. It also means that the FDA has not yet approved this study intervention for your type of cancer.
All participants on this study are treated in an identical manner. The investigators are doing this study because there continues to be a significant risk of relapse of disease after reduced intensity transplantation. In studies which have compared transplants using high-doses of chemotherapy and/or radiation versus reduced intensity transplants, patients undergoing reduced intensity transplants appear to have higher rates of relapse, but lower rates of toxicity and complication. This study attempts to utilize clofarabine, a newer chemotherapy agent shown to be quite active in AML, ALL, and MDS, to increase the anti-tumor effects of the conditioning regimen without accumulating unacceptable toxicity.
The reduced intensity allogeneic stem cell transplantation procedure involves giving you chemotherapy in relatively less intense doses to suppress your immune system. This is followed by an infusion of healthy blood stem cells from a matched related donor or a matched unrelated volunteer donor. It is hoped that these donor cells can eventually then attack any cancer cells which remain.
In this research study, the investigators are looking to see how well this new combination of busulfan and clofarabine works in reduced intensity allogeneic stem cell transplantation. By "works" the investigators mean to analyze safety, ability of donor cells to engraft (take hold), as well as measures of complications including toxicity, infections, graft-vs-host disease (GVHD), and relapse.
Detailed description
You will start the conditioning regimen, which is also called the preparative regimen. Conditioning is done to kill more cancer cells which may remain as well as prepare your body for transplant. You will receive the conditioning drugs into a vein. The conditioning regimen consists of the following drugs: Busulfan and Clofarabine.
While you are in the hospital you will have regular physical exams and you will be asked specific questions about any problems that you might be having. You will also have blood tests every day to look at how your bone marrow is recovering, to give possible transfusional support, and how to see how your liver and kidneys are functioning.
You will receive the following drugs before and after the allogeneic stem cell transplant: Neupogen (G-CSF) injections, drugs to prevent infections, Tacrolimus to prevent GVHD and Methotrexate.
You will have routine and regular follow-up in the transplant clinic after discharge from the hospital. The following will be performed at each visit:
Physical exam to monitor your health and check for signs of GVHD, infections and any side effects you may be having; Blood draw for routine blood tests to measure your blood cell count and chemistry; Blood tests to see if the transplanted stem cells are being accepted and are growing in the body (engraftment); Bone marrow biopsy to see the status of the underlying disease (to be done around 100 days after the stem cell transplant).
You will be asked to return to the clinic, at a minimum, for follow-up visits at 6 months, 9 months, 12 months, 18 months and 24 months after your stem cell transplant.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BuClo RIC + SCT | Experimental | Drug: Busulfan, Drug: Clofarabine, Procedure: Allogeneic Stem Cell InfusionBusulfan and Clofarabine (BuClo) reduced intensity conditioning (RIC) followed by allogeneic stem cell Transplantation (SCT) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Must have well-matched adult donor willing to donate peripheral blood stem cells with well-matched defined as 8/8 matched related or unrelated donor
- Adequate organ functioning
Key exclusion criteria (3 listed)
- Pregnant or breastfeeding
- Psychiatric disease severely impairing the compliance of the patient to participate in the study and/or give informed consent
- Evidence of prior exposure to HIV or HCV
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 |
|---|---|---|
| BusulfanBusulfan as part of reduced intensity conditioning prior to allogeneic stem cell transplantation | Drug | BuClo RIC + SCT |
| ClofarabineClofarabine as part of reduced intensity conditioning prior to allogeneic stem cell transplantation | Drug | BuClo RIC + SCT |
| Allogeneic Stem Cell InfusionAllogeneic stem cell transplantation after reduced intensity conditioning with busulfan / clofarabine chemotherapy | Procedure or surgery | BuClo RIC + SCT |
Primary outcome
Assessment of Donor Stem Cell Engraftment: ANC Count
Time frame: 1, 2, 3, and 4 weeks after transplantation
Patients are considered to have achieved donor cell engraftment if they have an absolute neutrophil count (ANC) of at least 500 cells/uL of blood for 3 consecutive measurements and at least 75% of hematopoietic elements are donor-derived as determined by chimerism assays from peripheral blood prior to day +40 after Busulfan/Clofarabine (BuClo) reduced intensity allogeneic stem cell transplantation
Donor Stem Cell Engraftment: Platelet Count
Time frame: 1, 2, 3, 4, 8, and 14 weeks post transplant
Platelet recovery was defined as having a platelet count of at least 20,000 platelets/uL of blood on 2 consecutive measurements without transfusional support prior to day +100 after BuClo RIC HSCT.
7 secondary outcomes
Cumulative Incidence of Non-relapse Mortality
Time frame: 100 days, 1 year
Progression-Free and Overall Survival
Time frame: 1 year, 2 years
Cumulative Incidence and Severity of Acute GVHD Within 100 Days Post Transplant
Time frame: 100 days
Cumulative Incidence of Chronic GVHD at One Year
Time frame: 1 year
Incidence of Hepatic Veno-occlusive Disease
Time frame: 2 years
Grade 3 or 4 Toxicities
Time frame: 2 years
Infection-related Complications
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 13 Jul 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.
Yi-Bin Chen, MD principal investigator
Massachusetts General Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Busulfan, Clofarabine and Allogeneic Stem Cell Infusion in people with Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia, run by Massachusetts General Hospital at 3 sites 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 2 inclusion and 3 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 13 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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 13 Jul 2017). 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?
Assessment of Donor Stem Cell Engraftment: ANC Count (time frame: 1, 2, 3, and 4 weeks after transplantation). The study lists 2 primary outcomes in all. 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 13 Jul 2017; AzTrials last refreshed its copy on 1 Nov 2026.