Safety Study of Bone Marrow Transplant Using Mismatched Tissue Followed by Chemotherapy
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|ClinicalTrials.gov Identifier: NCT00796562|
Recruitment Status : Completed
First Posted : November 24, 2008
Results First Posted : March 14, 2019
Last Update Posted : March 14, 2019
|Condition or disease||Intervention/treatment||Phase|
|MDS Leukemias Lymphomas||Drug: Busulfan Drug: Cyclophosphamide Radiation: Total body irradiation||Phase 2|
Allogeneic blood or marrow transplantation (alloBMT), following either marrow-ablative or nonmyeloablative conditioning, is a potentially curative treatment for a variety of hematologic malignancies and non-malignant hematologic disorders. Of all the potential sources of allografts, transplantation of stem cells from a human leukocyte antigen (HLA)-matched sibling has generally produced the best overall outcomes, i.e. overall and progression-free survival. Unfortunately, only about a third of candidates for alloBMT have HLA-matched siblings.
For patients who lack HLA-matched siblings, there are three alternative sources of stem cells for alloBMT: 1) volunteer unrelated donors; 2) umbilical cord blood; and 3) partially HLA-mismatched, or haploidentical, related donors. Since any patient shares exactly one HLA haplotype with each biological parent or child and half of siblings, an eligible haploidentical donor can be identified rapidly in nearly all cases. However, haploidentical BMT has been associated with significant risks of graft rejection and severe GVHD, which are manifestations of excessive alloreactivity by host and donor T cells, respectively.
The risk of severe GVHD may be reduced in intensively conditioned recipients of grafts that have been rigorously depleted of mature T cells or selectively depleted of alloreactive T cells, but the risks of serious infection and death from prolonged immune compromise in these patients remains high. Cyclophosphamide(Cy) is a highly immunosuppressive antineoplastic agent that has an established role in conditioning for alloBMT.
Typically, the drug is administered prior to transplantation to prevent graft rejection by suppressing the host immune system. However, pre-transplantation conditioning with Cy increases the risk of GVHD following allogeneic T cell infusion in mouse models. In contrast, administration of a properly timed, high dose of Cy after BMT inhibits both graft rejection and GVHD.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||107 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Trial of Myeloablative Conditioning and Transplantation of Partially HLA-mismatched Bone Marrow for Patients With Hematologic Malignancies|
|Actual Study Start Date :||December 2008|
|Actual Primary Completion Date :||June 2014|
|Actual Study Completion Date :||November 2016|
Experimental: Myeloablative haploidentical BMT
Participant will receive Busulfan injections, 4 times a day for 4 days with dilantin prophylaxis (in patients 10 years of age or older). Busulfan levels in the blood will be measured and dose adjusted, if needed.
Patient will receive Cy by IV once a day for 2 days.
Radiation: Total body irradiation
Patients will receive TBI once a day for 4 days.
Other Name: TBI
- Engraftment as Measured by Donor Chimerism [ Time Frame: Day 60 ]Percentage of participants who achieved donor chimerism >=95%.
- Non-relapse Mortality [ Time Frame: Day 100, 1 year ]Number of participants deceased for reasons other than disease relapse or progression.
- Acute GVHD [ Time Frame: Day 100 ]
Percentage of participants who experience grade II-IV or III-IV acute graft-versus-host-disease (GVHD) by Przepiorka criteria. The stages are defined as follows:
- Stage II: Rash on >50% of skin, bilirubin 2-3 mg/dL, or diarrhea 500-1000 mL/day
- Stage III: Bilirubin 3-15 mg/dL or diarrhea >1000 mL/day
- Stage IV: Generalized erythroderma with bullae or bilirubin >15 mg/dL This outcome was estimated using proportional subdistribution hazard regression model for competing risks (Fine and Gray 1999)
- Chronic GVHD [ Time Frame: 6 months, 12 months ]Percentage of participants who experience chronic GVHD. Chronic GVHD is graded using NIH consensus criteria and Seattle criteria. This outcome was estimated using proportional subdistribution hazard regression model for competing risks (Fine and Gray 1999)
- Survival [ Time Frame: 1 year, 2 years, 3 years ]Percentage of participants alive (overall survival) and alive without disease relapse, progression, or diagnosis of myeloid malignancy (event-free survival). Estimated using Kaplan-Meier method.
- Relapse [ Time Frame: 1 year, 3 years ]Percentage of participants who experienced disease progression or relapse. This outcome was estimated using proportional subdistribution hazard regression model for competing risks (Fine and Gray 1999)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00796562
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center|
|Baltimore, Maryland, United States, 21231|
|The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Baltimore, Maryland, United States, 21231|
|Principal Investigator:||Heather Symons, M.D.||Johns Hopkins University|