Haploidentical Bone Marrow Transplant With Post-Transplant Cyclophosphamide for Patients With Severe Aplastic Anemia

Severe Aplastic Anemia Clinical Trial

Official title:

A Study of T-Cell Replete, HLA-Mismatched Haploidentical Bone Marrow Transplantation With Post-Transplant Cyclophosphamide for Patients With Severe Aplastic Anemia Lacking HLA-Matched Related Donor

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02828592
• Other study ID #: NSH 1158
• Status: Recruiting
• Phase: Phase 2
• Start date: September 9, 2016
• Est. completion date: August 31, 2026

Study information

• Verified date: April 2024
• Source: Northside Hospital, Inc.
• Contact: Melhem Solh, MD
• Phone: 404-255-1930
• Email: msolh[@]bmtga.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Severe aplastic anemia is a rare and serious form of bone marrow failure related to an immune-mediated mechanism that results in severe pancytopenia and high risk for infections and bleeding. Patients with matched sibling donors for transplantation have a 80-90% chance of survival; however, a response rate with just immunosuppression for those patients lacking suitable HLA-matched related siblings is only 60%. With immunosuppression, only 1/3 of patients are cured, 1/3 are dependent on long term immunosuppression, and the other 1/3 relapse or develop a clonal disorder. Recent studies have shown that using a haploidentical donor for transplantation has good response rates and significantly lower rates of acute and chronic GVHD.

Description:

Mismatched haploidentical donors will be identified for patients with severe aplastic anemia. These patients will undergo a preparative regimen of Fludarabine/Cyclophosphamide/TBI followed by haploidentical bone marrow transplantation. Post-transplant Cyclophosphamide will be administered on Days 3 & 4. Immunosuppression with Tacrolimus and MMF will begin on Day +5; MMF will be discontinued on Day +35 while Tacrolimus continues until Day +180. Investigators hypothesize that haploidentical transplantation with the above-mentioned preparative regimen will have a <30% graft failure rate. The one-sided exact Binomial test at 5% significance level will be used to test this hypothesis. The size of 20 patients provides the power of 92.5% for confirming the 30-day graft failure rate <30%.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: August 31, 2026
• Est. primary completion date: August 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 75 Years

Eligibility

Inclusion Criteria:

• Availability of 3/6 - 5/6 matched (HLA-A, B, DR) related donor who must have negative HLA cross-match in the host vs. graft direction

• Age <= 65 years for previously treated and <= 75 years for previously treated patients

• KPS >= 70%

• Aplastic Anemia that meets the following criteria:

Peripheral Blood (must fulfill 2 of 3):

• <500 PMN/mm3

• <20,000 platelets

• absolute reticulocyte count <40,000/microL

Bone Marrow (must be either):

• markedly hypocellular (<25% of normal cellularity)

• moderately hypocellular with 70% non-myeloid precursors and patient meets peripheral blood criteria above

Exclusion Criteria:

• poor cardiac function (LVEF <40%)

• poor pulmonary function (FEV1 & FVC <50% predicted)

• poor liver function (bili >= 2mg/dL)

• poor renal function (creatinine >= 2.0mg/dL or creatinine clearance <40mL/min)

• prior allogeneic transplant

Related Conditions & MeSH terms

• Anemia
• Anemia, Aplastic
• Severe Aplastic Anemia

Intervention

Drug:
• Fludarabine
30 mg/m2 IV QD x 5 days (Days -6 to -2)
• Cyclophosphamide
14.5 mg/kg/day IV x 2 doses (Days -6 & -5)

Radiation:
• Total Body Irradiation
300 cGy x1 dose (Day -1)

Drug:
• Rabbit ATG
1.5 mg/kg/day x 3 days (Days -3 to -1)
• Cyclophosphamide
Post-transplant: 50 mg/kg IV QD (Day +3 to +4)

Locations

Country	Name	City	State
United States	Blood and Marrow Transplant Group of Georgia	Atlanta	Georgia
United States	Northside Hospital	Atlanta	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Northside Hospital, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (9)

Atta EH, de Sousa AM, Schirmer MR, Bouzas LF, Nucci M, Abdelhay E. Different outcomes between cyclophosphamide plus horse or rabbit antithymocyte globulin for HLA-identical sibling bone marrow transplant in severe aplastic anemia. Biol Blood Marrow Transp — View Citation

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 — View Citation

Bashey A, Zhang X, Jackson K, Brown S, Ridgeway M, Solh M, Morris LE, Holland HK, Solomon SR. Comparison of Outcomes of Hematopoietic Cell Transplants from T-Replete Haploidentical Donors Using Post-Transplantation Cyclophosphamide with 10 of 10 HLA-A, -B — View Citation

Brodsky RA, Chen AR, Dorr D, Fuchs EJ, Huff CA, Luznik L, Smith BD, Matsui WH, Goodman SN, Ambinder RF, Jones RJ. High-dose cyclophosphamide for severe aplastic anemia: long-term follow-up. Blood. 2010 Mar 18;115(11):2136-41. doi: 10.1182/blood-2009-06-225375. Epub 2009 Dec 16. — View Citation

Rozman C, Marin P, Nomdedeu B, Montserrat E. Criteria for severe aplastic anaemia. Lancet. 1987 Oct 24;2(8565):955-7. doi: 10.1016/s0140-6736(87)91432-2. — View Citation

Scheinberg P, Young NS. How I treat acquired aplastic anemia. Blood. 2012 Aug 9;120(6):1185-96. doi: 10.1182/blood-2011-12-274019. Epub 2012 Apr 19. — View Citation

Socie G. Allogeneic BM transplantation for the treatment of aplastic anemia: current results and expanding donor possibilities. Hematology Am Soc Hematol Educ Program. 2013;2013:82-6. doi: 10.1182/asheducation-2013.1.82. — View Citation

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 — View Citation

Young NS. Current concepts in the pathophysiology and treatment of aplastic anemia. Hematology Am Soc Hematol Educ Program. 2013;2013(1):76-81. doi: 10.1182/asheducation-2013.1.76. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Demonstrate sustained engraftment after T-cell replete HLA-mismatched haploidentical bone marrow transplantation by collecting chimerism tests monthly following transplant	Hypothesis is that following preparative regimen and bone marrow transplantation, the 30-day graft failure rate will be <30%.	2 years
Secondary	Determine the incidence of regimen-related mortality at 100 days post transplantation by recording treatment-related adverse events		2 years
Secondary	Determine the incidence of grade 2-4 and 3-4 acute graft versus host disease at 100 days post transplantation by assessing signs and symptoms of GVHD throughout post-transplant course		2 years
Secondary	Determine incidence of chronic GVHD at 6 months and 1 year post transplantation by assessing signs and symptoms of GVHD throughout post-transplant course		2 years
Secondary	Estimate overall survival at 100 days and 1 year post transplantation by collecting survival information at those time points		2 years