Reduced Intensity Conditioning Transplant Using Haploidentical Donors
This trial will evaluate the safety and efficacy of a reduced intensity allogeneic HSCT from partially HLA-mismatched first-degree relatives utilizing PBSC as the stem cell source. The primary objective of the study is to estimate the incidence of graft rejection and acute GVHD. A secondary objective will be to estimate the incidence of the relapse, NRM, OS, chronic GVHD and EFS.
|Condition or Disease||Intervention/Treatment||Phase|
Patients will receive a haploidentical transpalnt using a fludarabine melphalan prepartive regimen. Patients will get cyclophosphamide on days 3 & 4 post-transplant.
Arms and Interventions
|Experimental: Reduced-Intensity Mismatched Transplant|
Fludarabine, Melphalan & Post-transplant cyclophosphamide
fludarabine (30mg/m2) given every day starting on Day -6 through Day -2;
cyclophosphamide (50mg/kg) given every day starting on Day 3 through Day 4.
Procedure: peripheral blood stem cell transplant
Primary Outcome Measures
- Graft Rejection [100 days]
Secondary Outcome Measures
- Overall Survival [100 days]
- Overall survival [1 year]
- Relapse incidence [100 days]
- Relapse incidence [1 year]
- GVHD incidence [100 days]
- GVHD incidence [1 year]
No available matched related or unrelated donor, OR a matched related or unrelated donor will not be available in time frame necessary to perform potentially curative transplant
Availability of 3/6 - 5/6 matched (HLA-A, B, DR) related donor (donor must have negative HLA cross-match in host vs. graft direction)
Karnofsky status ≥70%
One of the following high-risk malignancies:
Chronic Myelogenous Leukemia: Chronic myelogenous leukemia in chronic phase, resistant or intolerant to available tyrosine kinase inhibitors; Chronic myelogenous leukemia in accelerated phase; Chronic myelogenous leukemia with blast crisis that has entered into a second chronic phase following induction chemotherapy
Acute Myelogenous Leukemia in first or greater remission
Myelodysplastic Syndrome at least one of the following: treatment-related; monosmy 7, complex cytogenetics or other high risk karyotype; IPSS score of 1.0 or greater; neutropenia or cytopenia requiring transfusion not responding to therapy; peripheral or BM blast count of <10%; CMML
Acute lymphocytic leukemia/lymphoblastic lymphoma: 2nd or subsequent complete remission; first complete remission; marrow blasts <5%, but persistence of minimal residual disease by flow cytometry, cytogenetics, or FISH
Chronic Lymphocytic Leukemia/Prolymphocytic Leukemia: previously treated disease that has either relapsed or failed to respond adequately to conventional-dose therapy including purine analogs
Hodgkin's or Non-Hodgkin's Lymphoma (including low-grade, mantle cell, and intermediate-grade/diffuse): previously treated disease that has either relapsed or failed to respond adequately to conventional-dose therapy or autologous transplantation
Myeloproliferative diseases (myelofibrosis, CMML)
Multiple Myeloma with relapse after a prior autologous transplant or eligible for allogeneic HSCT based on other risk factors
not be excluded on basis of sex, racial, or ethnic backgrounds
poor cardiac function: left ventricular ejection fraction <40%
poor pulmonary function: FEV1 and FVC <50% predicted
poor liver function: bilirubin >2 mg/dl (not due to hemolysis, Gilbert's or primary malignancy)
poor renal function: Creatinine >2.0mg/dl or creatinine clearance (calculated creatinine clearance is permitted) < 40 mL/min based on Traditional Cockcroft-Gault formula: 140 - age (yrs) x Smaller of Actual Weight vs. Ideal Body Weight (kg) / 72 x Serum creatinine (mg/dl)
prior allogeneic transplant
women of childbearing potential who currently are pregnant or who are not practicing adequate contraception
any debilitating medical or psychiatric illness which would preclude their giving informed consent or their receiving optimal treatment and follow-up
Contacts and Locations
|1||Northside Hospital||Atlanta||Georgia||United States||30342|
Sponsors and Collaborators
- Northside Hospital, Inc.
- Blood and Marrow Transplant Group of Georgia
- Principal Investigator: Melhem Solh, MD, Northside Hospital
Study Documents (Full-Text)None provided.
- Aversa F, Terenzi A, Tabilio A, Falzetti F, Carotti A, Ballanti S, Felicini R, Falcinelli F, Velardi A, Ruggeri L, Aloisi T, Saab JP, Santucci A, Perruccio K, Martelli MP, Mecucci C, Reisner Y, Martelli MF. Full haplotype-mismatched hematopoietic stem-cell transplantation: a phase II study in patients with acute leukemia at high risk of relapse. J Clin Oncol. 2005 May 20;23(15):3447-54. Epub 2005 Mar 7.
- Bashey A, Solomon SR. T-cell replete haploidentical donor transplantation using post-transplant CY: an emerging standard-of-care option for patients who lack an HLA-identical sibling donor. Bone Marrow Transplant. 2014 Aug;49(8):999-1008. doi: 10.1038/bmt.2014.62. Epub 2014 May 19. Review.
- O'Donnell PV, Luznik L, Jones RJ, Vogelsang GB, Leffell MS, Phelps M, Rhubart P, Cowan K, Piantados S, Fuchs EJ. Nonmyeloablative bone marrow transplantation from partially HLA-mismatched related donors using posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2002;8(7):377-86.
- Solomon SR, Sizemore CA, Sanacore M, Zhang X, Brown S, Holland HK, Morris LE, Bashey A. Haploidentical transplantation using T cell replete peripheral blood stem cells and myeloablative conditioning in patients with high-risk hematologic malignancies who lack conventional donors is well tolerated and produces excellent relapse-free survival: results of a prospective phase II trial. Biol Blood Marrow Transplant. 2012 Dec;18(12):1859-66. doi: 10.1016/j.bbmt.2012.06.019. Epub 2012 Aug 1.
- Solomon SR, Sizemore CA, Sanacore M, Zhang X, Brown S, Holland HK, Morris LE, Bashey A. Total Body Irradiation-Based Myeloablative Haploidentical Stem Cell Transplantation Is a Safe and Effective Alternative to Unrelated Donor Transplantation in Patients Without Matched Sibling Donors. Biol Blood Marrow Transplant. 2015 Jul;21(7):1299-307. doi: 10.1016/j.bbmt.2015.03.003. Epub 2015 Mar 19.
- NSH 1132