Study of Fludarabine Based Conditioning for Allogeneic Stem Cell Transplantation for Myelofibrosis
Stem cell transplantation is used to treat may types of diseases. There a 2 types of transplants, conventional (very intense) and reduced intensity-non-myeloablative, also called mini-transplants.
This study proposes to use a conditioning regimen for allogeneic transplantation along with a reduced intensity transplant. Conditioning regiment is the name for the combination of chemotherapy drugs that is given to patients before receiving a transplantation of donor stem cells. It is hoped that the regimen designed for this study proves to be less toxic and has an equal or better anticancer effect than the regimens that are normally used. The regimen being used is a combination of two chemotherapy drugs, fludarabine and melphalan. This regimen has been studied in recipients of matched sibling transplants and in recipients of alternative donor stem cells in other hematologic malignancies. Those subjects, who receive stem cells from an unrelated donor, will also receive and additional drug called ATG or anti thymocyte globulin. ATG suppresses the immune system, thus reducing the chances for the recipient rejecting the transplant (graft).
The purpose of this study is to observe if reduced intensity transplants can be used to allow engraftment or "take" of the donor's bone marrow. Studies conducted in the past show this type of transplant is much less toxic than traditional bone marrow transplants. Reduced intensity transplants may be better tolerated by patients who may experience serious side effects from standard (very intense) stem cell transplant.
The study has been recently amended to follow all subjects for survival.
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Study of Fludarabine Based Conditioning for Allogeneic Stem Cell Transplantation for Myelofibrosis|
- The Primary Endpoint is Progression-free Survival. [ Time Frame: 2 years ] [ Designated as safety issue: No ]Number of participants alive at 2 years who are progression-free
- Response Outcomes [ Time Frame: 180 days ] [ Designated as safety issue: No ]assessed according to the IWG Criteria
- Overall Survival [ Time Frame: 73 months ] [ Designated as safety issue: No ]The number of patients alive at last follow-up.
- Absolute Neutrophil Count (ANC) [ Time Frame: 2 years ] [ Designated as safety issue: No ]Patients with ANC ≥0.5 × 10^9/L
- PLT [ Time Frame: 2 years ] [ Designated as safety issue: No ]Patients with PLT ≥20 × 109/L
- Transplant-related Mortality [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]Transplant-related Mortality including Graft-versus-host disease (GVHD)
|Study Start Date:||August 2007|
|Estimated Study Completion Date:||August 2020|
|Primary Completion Date:||August 2011 (Final data collection date for primary outcome measure)|
Experimental: Fludarabine, Melphalan +/- ATG
Fludarabine, Melphalan +/- ATG
Drug: Fludarabine, Melphalan +/- ATG
Conditioning regimen for Allogenic Stem Cell Transplant:
Related Donor Fludarabine days -6 to -2 (30mg/m2 IVPB over 30 minutes daily) Melphalan days -3 to -2 (70mg/m2 IVPB over 30 minutes daily)
Unrelated Donor Fludarabine days -6 to -2 (30mg/m2 IVPB over 30 minutes daily) Melphalan days -3 to -2 (70mg/m2 IVPB over 30 minutes daily) ATG (Thymoglobulin®) days -3 to -1 (0.5 mg/kg IV on day -3 [given over 6 hours], and 2 mg/kg on days -2 and -1 [given over 4 hours])
This study is designed as a single arm Phase II clinical trial in patients with myelofibrosis who are eligible for transplantation from a related donor or from an unrelated donor source. Patients will be accrued into two separate strata defined by donor type. Each of the two strata will be analyzed separately.
Patients will be followed yearly from time of enrollment into the study to assess clinical response and overall, progression and event free survival, as well as incidence and degree of acute and chronic GVHD. We will estimate cumulative survival and transplant related mortality in patients enrolled in each of the two strata.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00572897
|United States, Illinois|
|University of Illinois at Chicago|
|Chicago, Illinois, United States, 60612|
|United States, Maryland|
|Baltimore, Maryland, United States, 21205|
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263|
|Icahn School of Medicine at Mount Sinai|
|New York, New York, United States, 10029|
|Weill Cornell Medical College|
|New York, New York, United States, 10065|
|United States, Ohio|
|Ohio State Univesity|
|Columbus, Ohio, United States, 43210|
|United States, Utah|
|University of Utah|
|Salt Lake City, Utah, United States, 84132|
|Princess Margaret Hospital|
|Toronto, Ontario, Canada, M5G2M9|
|University of Florence|
|Florence, IL, Italy, 60302|
|Ospedali Riuniti di Bergamo|
|Bergamo, Italy, 24128|
|University of San Martino|
|San Martino, Italy|
|Regionala etikprovningsnamnden Goteborg|
|Goteborg, Sweden, 60302|
|Principal Investigator:||John Mascarenhas, MD||Icahn School of Medicine at Mount Sinai|
|Study Chair:||Giovanni Barosi, MD||Myeloproliferative Disorders-Research Consortium|
|Study Chair:||Damiano Rondelli, MD||Myeloproliferative Disorders-Research Consortium|