Clinical trial NCT01643668: Busulfan/Clofarabine + Allogeneic Stem Cell Transplantation
Official title: Phase II Study of Reduced Intensity Conditioning With Busulfan/Clofarabine Followed by Allogeneic Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Acute Lymphoblastic Leukemia
Myelodysplastic Syndrome
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2012-07-18
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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. "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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Assessment of Donor Stem Cell Engraftment: ANC Count
timeFrame: 1, 2, 3, and 4 weeks after transplantation
measure: Donor Stem Cell Engraftment: Platelet Count
timeFrame: 1, 2, 3, 4, 8, and 14 weeks post transplant
Secondary outcomes:
measure: Cumulative Incidence of Non-relapse Mortality
timeFrame: 100 days, 1 year
measure: Progression-Free and Overall Survival
timeFrame: 1 year, 2 years
measure: Cumulative Incidence and Severity of Acute GVHD Within 100 Days Post Transplant
timeFrame: 100 days
measure: Cumulative Incidence of Chronic GVHD at One Year
timeFrame: 1 year
measure: Incidence of Hepatic Veno-occlusive Disease
timeFrame: 2 years
measure: Grade 3 or 4 Toxicities
timeFrame: 2 years
measure: Infection-related Complications
timeFrame: 2 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Yi-Bin Chen, MD
role: PRINCIPAL_INVESTIGATOR
References: