Non-Myeloablative Conditioning and Bone Marrow Transplantation

Not Applicable

Active, not recruiting

Interventions: Drug: Thymoglobulin
Drug: Fludarabine
Drug: Cyclophosphamide (CTX)
Drug: Mesna
Drug: Sirolimus
Drug: Mycophenolate mofetil (MMF)
Procedure: Bone marrow transplantation
Radiation: Total body irradiation

Brief Summary: Allogeneic blood or marrow transplantation (alloBMT) is a curative therapy for a variety of hematologic disorders, including sickle cell disease and thalassemia. Even when it is clear that alloBMT can give to these patients an improvement in their disease, myeloablative transplants have important toxicities and mortalities associated. The lack of suitable donors continues to be a limit to access to transplantation. Substantial progress has been made recently in the development of pre-treatment regimens that facilitate the sustained engraftment of donor marrow with reduced toxicity. Most of these regimens incorporate highly immunosuppressive drugs, which allow the reduction or elimination of myeloablative agents or total body irradiation without endangering the sustained engraftment of HLA-identical allogeneic stem cells. Preliminary results of non-myeloablative allogeneic stem cell transplantation suggest that the procedure can be performed in patients who are ineligible for myeloablative alloBMT, and that sustained remissions of several hematologic malignancies can be obtained.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Non-Myeloablative Conditioning and Bone Marrow Transplantation	Bone marrow transplantation	-
Non-Myeloablative Conditioning and Bone Marrow Transplantation	Total body irradiation	-
Non-Myeloablative Conditioning and Bone Marrow Transplantation	Fludarabine	-
Non-Myeloablative Conditioning and Bone Marrow Transplantation	Mesna	-
Non-Myeloablative Conditioning and Bone Marrow Transplantation	Cyclophosphamide (CTX)	-
Non-Myeloablative Conditioning and Bone Marrow Transplantation	Sirolimus	-
Non-Myeloablative Conditioning and Bone Marrow Transplantation	Mycophenolate mofetil (MMF)	-
Non-Myeloablative Conditioning and Bone Marrow Transplantation	Thymoglobulin	-

Primary Outcome Measures

Name	Time	Method
Transplant-related Mortality (TRM)	at 1 year after BMT	Defined as death in the absence of recurrent sickle cell disease or hemoglobinopathy

Secondary Outcome Measures

Name	Time	Method
Number of Patients Who Developed Grade I-IV Acute Graft-vs.-Host Disease	2 years	GVHD Severity was graded using the established National Institutes of Health's consensus criteria \[36\].
Number of Patients With Donor Hematopoietic Chimerism in Peripheral Blood <95% at 6 Months After Mini-haploBMT	Up to approximately 180 after mini-haploBMT	Partially human leukocyte antigen (HLA)-mismatched bone marrow from first-degree relatives. Defined in percentages of donor cells in patient's peripheral blood, measured in 4 ways. * Mixed donor chimerism: \> 0% but \< 95% * Complete donor chimerism \> 95% Any amount of donor chimerism after day 60 will be considered as having engrafted
Number of Participants With Hematologic and Non-hematologic Toxicities Following minihaploBMT	Day 60 after BMT	Hematologic toxicity: -Absolute neutrophil count (ANC): consecutive values of \< 500/µL on 3 different days after chemotherapy post-BMT Platelet count: consecutive values of \< 20,000 µL on 3 different days after chemotherapy post-BMT Non-hematologic toxicities: -Toxicities necessitating hospitalization Toxicities grade 4 or above Meets the criteria of the following SAE: * Relapse of underlying disease * Grade 3 ocular toxicity not related to ocular GVHD * Grade 3 related non-hematologic toxicity

Locations (3): Vanderbilt-Ingram Cancer Center
🇺🇸
Nashville, Tennessee, United States
Saint-Louis Hospital
🇫🇷
Paris, France
St Mary's Hospital
🇬🇧
London, United Kingdom