Double Cord Versus Haploidentical (Blood and Marrow Transplant Clinical Trials Network #1101)
Hematopoietic cell transplants (HCT)are one treatment option for people with leukemia or lymphoma. Family members,unrelated donors or banked umbilical cordblood units with similar tissue type can be used for HCT. This study will compare the effectiveness of two new types of bone marrow transplants in people with leukemia or lymphoma: one that uses bone marrow donated from family members with only partially matched bone marrow; and, one that uses two partially matched cord blood units.
Acute Lymphocytic Leukemia
Acute Myelogenous Leukemia
Mantle Cell Lymphoma
Drug: Biological/Vaccine: Haploidentical BMT
Drug: Double Cord Blood Transplantation
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Multi-Center, Phase III, Randomized Trial of Reduced Intensity (RIC) Conditioning and Transplantation of Double Unrelated Umbilical Cord Blood (dUCB) Versus HLA-Haploidentical Related Bone Marrow (Haplo-BM) for Patients With Hematologic Malignancies (BMT CTN #1101)|
- Progression free survival [ Time Frame: two years from the date of randomization ] [ Designated as safety issue: No ]The primary endpoint is PFS at 2-years from the date of randomization. PFS is defined as the time interval from date of randomization and time to relapse/progression, to death or to last follow-up.
- Neutrophil Recovery [ Time Frame: 56 days ] [ Designated as safety issue: No ]Neutrophil recovery is defined as achieving an ANC greater than or equal to 500/mm^3 for three consecutive measurements on three different days. The first of the three days will be designated the day of neutrophil recovery.
- Primary Graft Failure [ Time Frame: Day 56 ] [ Designated as safety issue: Yes ]Primary graft failure is defined as less than 5% donor chimerism on all measurements up to and including Day 56.
- Secondary Graft Failure [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]Secondary graft failure is defined as initial neutrophil recovery followed by neutropenia with less than 5% donor chimerism in the absence of recurrent disease. If chimerism assays were not performed and ANC less than 500/mm^3 is sustained , then it will be counted as a secondary graft failure.
- Platelet Recovery [ Time Frame: Days 100 and 180 ] [ Designated as safety issue: No ]Platelet recovery is defined by two different metrics as the first day of a sustained platelet count greater than 20,000/mm^3 or greater than 50,000/mm^3 with no platelet transfusions in the preceding seven days. The first day of the sustained platelet count will be designated the day of platelet engraftment.
- Donor Cell Engraftment [ Time Frame: Day 56 ] [ Designated as safety issue: No ]Donor cell engraftment is defined as donor chimerism greater than or equal to 5% on greater than or equal to Day 56 after transplantation. Chimerism may be evaluated in whole blood or blood cell fractions, including CD3 and CD33 or CD15 fractions). The actual measurement dates may be within +/- 7 days of the above recommended time points.
- Acute Graft-versus-Host Disease (aGVHD) [ Time Frame: Day 100, 6 months and annually through 3 years ] [ Designated as safety issue: No ]The cumulative incidences of grade II - IV and III - IV acute aGVHD will be determined. The time to onset of acute grades II-IV aGVHD and grades III-IV aGVHD will be recorded, as well as the maximum grade achieved.
- Chronic Graft-versus-Host Disease (cGHVD) [ Time Frame: Day 100, 6 months and annually through 3 years ] [ Designated as safety issue: No ]The cumulative incidence of cGVHD will be determined. Data will be collected directly from providers and chart review according to the recommendations of the NIH Consensus Conference. The NIH global severity scores of mild, moderate and severe chronic GVHD will be assessed.
- Overall Survival [ Time Frame: Anually through Year 3 ] [ Designated as safety issue: No ]Overall survival is defined as the time interval between date of randomization and death from any cause or for surviving patients, to last follow-up.
- Treatment-related Mortality (TRM) [ Time Frame: Day 100, 6 months and years 1 and 2 ] [ Designated as safety issue: Yes ]The cumulative incidence of TRM will be estimated at Days 100, 180, and at 1 and 2 years after transplantation. An event for this endpoint is death without evidence of disease progression or recurrence.
- Infections [ Time Frame: Over the 3 year follow up period ] [ Designated as safety issue: No ]All Grade 2 and 3 infections will be reported.Grade 1 CMV infections through Day 56 will also be reported.
|Study Start Date:||June 2012|
|Estimated Study Completion Date:||June 2019|
|Estimated Primary Completion Date:||June 2018 (Final data collection date for primary outcome measure)|
Experimental: Haplo-BM Transplantation
Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen.
Drug: Biological/Vaccine: Haploidentical BMT
The conditioning regimen consists of:
Fludarabine (Flu)30 mg/m2 IV Days -6, -5, -4, -3, -2 Cyclophosphamide (Cy) 14.5 mg/kg IV Days -6, -5 Total body irradiation (TBI) 200cGy Day -1
The GVHD prophylaxis regimen consists of:
Cy 50 mg/kg IV Days 3, 4 Tacrolimus (IV or PO) beginning Day 5 Mycophenolate mofetil (MMF) 15 mg/kg po TID, maximum dose 1 g po TID beginning Day 5 until Day 35
Experimental: dUCB Transplantation
Participants will receive a double umbilical cord blood transplant using a reduced intensity conditioning regimen.
Drug: Double Cord Blood Transplantation
The preparative regimen consists of:
Fludarabine 40 mg/m2 IV Days -6, -5, -4,-3, -2 Cyclophosphamide 50 mg/kg IV Day -6 Total Body Irradiation (TBI) 200 cGy Day -1
The GVHD prophylaxis regimen consists of:
Cyclosporine beginning Day -3 with dose adjusted to maintain a trough level of 200-400 ng/mL.
Mycophenolate mofetil (MMF) 15 mg/kg po TID, maximum dose 1 g po TID beginning Day -3 until Day 35
Reduced intensity conditioning (RIC) blood or marrow transplantation (BMT) has allowed older and less clinically fit patients to receive potentially curative treatment with allogeneic HCT for high risk or advanced hematological malignancies. Patients lacking an HLA-matched sibling may receive a graft from a suitably HLA-matched unrelated donor. However, up to a third of patients will not have an HLA-matched sibling or a suitably matched adult unrelated donor (i.e., no more than a mismatch at a single locus). Even when a suitably matched unrelated donor is identified, data from the National Marrow Donor Program (NMDP) indicate that a median of four months is required to complete searches that result in transplantation; thus, some number of patients succumb to their disease while awaiting identification and evaluation of a suitably matched adult unrelated donor.
Single or dual center studies have shown that partially HLA-mismatched related bone marrow (haplo-BM) and unrelated double umbilical cord blood (dUCB) are valuable sources of donor cells for RIC HCT, thus extending this treatment modality to patients who lack other donors. In order to study the reproducibility, and thus, the wider applicability of these two alternative donor strategies, The Blood and Marrow Transplantation Clinical Trials Network (BMT CTN) conducted two parallel multicenter prospective Phase II clinical trials. These two studies evaluated the safety and efficacy of related haplo-BM (BMT CTN 0603) and dUCB (BMT CTN 0604) transplantation after RIC. Both of these alternative donor approaches produced early results similar to that reported with unrelated donor, and even HLA-matched sibling, HCT. These data demonstrate not only the efficacy of both of these approaches, but also that both can be safely exported from the single center setting. Both haplo-BM and dUCB grafts can be obtained rapidly for greater than 90% of patients lacking an HLA-matched donor. This study will test the hypothesis that progression free survival at two years after RIC haplo-BM transplantation is similar to the progression free survival after RIC dUCB transplantation.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01597778
|Contact: Sandi Sykes||301-251-1161 ext email@example.com|
Hide Study Locations
|United States, California|
|City of Hope National Medical Center||Recruiting|
|Duarte, California, United States, 91010-3000|
|Contact: Chatchada Karanes, MD 626-256-4673 Ckaranes@coh.org|
|Stanford Hospital and Clinics||Recruiting|
|Stanford, California, United States, 94305|
|Contact: Jonathan Benjamin, MD 650-723-0822 firstname.lastname@example.org|
|United States, Florida|
|University of Florida College of Medicine/Shands||Recruiting|
|Gainesville, Florida, United States, 32610-0277|
|Contact: John R Wingard, MD 352-273-8022 email@example.com|
|United States, Georgia|
|BMT Program at Northside Hospital||Recruiting|
|Atlanta, Georgia, United States, 30342|
|Contact: Lawrence Morris, MD firstname.lastname@example.org|
|Atlanta, Georgia, United States, 30322|
|Contact: Edmund Waller, MD email@example.com|
|United States, Kansas|
|University of Kansas Hospital||Recruiting|
|Kansas City, Kansas, United States, 66160|
|Contact: Omar Aljitawi, MD 913-588-6029 firstname.lastname@example.org|
|United States, Maryland|
|Johns Hopkins University||Recruiting|
|Baltimore, Maryland, United States, 21231|
|Contact: Ephraim Fuchs, MD email@example.com|
|Principal Investigator: Ephraim Fuchs, MD|
|United States, Massachusetts|
|Dana Farber Cancer Institute, Brigham & Women's Hospital||Recruiting|
|Boston, Massachusetts, United States, 02115|
|Contact: Corey Cutler, MD 617-632-5946 firstname.lastname@example.org|
|United States, Minnesota|
|Univeristy of Minnesota||Recruiting|
|Minneapolis, Minnesota, United States, 55455|
|Contact: Claudio Brunstein, MD email@example.com|
|Principal Investigator: Claudio Brunstein, MD|
|United States, New York|
|University of Rochester Medical Center||Not yet recruiting|
|Rochester, New York, United States, 14642|
|Stony Brook University Medical Center||Not yet recruiting|
|Stony Brook, New York, United States, 11794-7122|
|Contact: Michael Sehuster, MD 631-444-3577 Michael.Sehuster@sbumed.org|
|United States, North Carolina|
|University of North Carolina Hospital at Chapel Hill||Recruiting|
|Chapel Hill, North Carolina, United States, 27599-7305|
|Contact: Thomas C Shea, MD 919-966-7313 firstname.lastname@example.org|
|Duke University Medical Center||Recruiting|
|Durham, North Carolina, United States, 27705|
|Contact: Joanne Kurtzberg, MD email@example.com|
|United States, Ohio|
|University Hospitals of Cleveland||Recruiting|
|Cleveland, Ohio, United States, 44106-5061|
|Contact: Hillard Lazarus, MD 216-844-3629 Hillard.Lazarus2@UHhospitals.org|
|Sub-Investigator: Rolla Abu-Arja, MD|
|Sub-Investigator: Paolo Caimi, MD|
|Sub-Investigator: Kenneth Cooke, MD|
|Sub-Investigator: Brenda Cooper, MD|
|Sub-Investigator: Marcos de Lima, MD|
|Sub-Investigator: Jane Little, MD|
|Sub-Investigator: Basem William, MD|
|Cleveland Clinic Foundation||Not yet recruiting|
|Cleveland, Ohio, United States, 44195|
|Contact: Matt Kalaycio, MD 216-444-3705 firstname.lastname@example.org|
|United States, Pennsylvania|
|University of Pennsylvania Cancer Center||Recruiting|
|Philadelphia, Pennsylvania, United States, 19104|
|Contact: Elizabeth Hexner, MD email@example.com|
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|Medical University of South Carolina||Recruiting|
|Charleston, South Carolina, United States, 29425|
|Contact: Luciano JM Costa, MD, PhD 843-792-4271 firstname.lastname@example.org|
|United States, Texas|
|Univesity of Texas, MD Anderson CRC||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Stefan Ciurea, MD email@example.com|
|United States, Virginia|
|Virginia Commonwealth University||Recruiting|
|Richmond, Virginia, United States, 23298|
|Contact: John McCarty, MD 804-828-4360 firstname.lastname@example.org|
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|Fred Hutchinson Cancer Research Center||Recruiting|
|Seattle, Washington, United States, 98109-1024|
|Contact: Paul O'Donnell, MD, PhD email@example.com|
|Principal Investigator: Paul O'Donnell, MD|
|United States, West Virginia|
|West Virginia University||Not yet recruiting|
|Morgantown, West Virginia, United States, 26506-9162|
|Contact: Michael Craig, MD firstname.lastname@example.org|
|Study Director:||Mary Horowitz, MD, MS||Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin|