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

NCT02828592 | Recruiting Phase 2

• 1 other identifier: NSH 1158
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Severe Aplastic Anemia

Keywords

SAA

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Determine the incidence of regimen-related mortality at 100 days post transplantation by recording treatment-related adverse events

  2 years

• 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

• 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

• Estimate overall survival at 100 days and 1 year post transplantation by collecting survival information at those time points

  2 years

Study Arms (1)

Flu/Cy/TBI

EXPERIMENTAL

Fludarabine, Cyclophosphamide, TBI followed by bone marrow transplantation. Post-transplant Cyclophosphamide will be on Days 3 \& 4.

Drug: Fludarabine; Drug: Cyclophosphamide; Radiation: Total Body Irradiation; Drug: Rabbit ATG

Interventions

Fludarabine DRUG

30 mg/m2 IV QD x 5 days (Days -6 to -2)

Flu/Cy/TBI

Cyclophosphamide DRUG

14.5 mg/kg/day IV x 2 doses (Days -6 \& -5)

Flu/Cy/TBI

Total Body Irradiation RADIATION

300 cGy x1 dose (Day -1)

Also known as: TBI

Flu/Cy/TBI

Rabbit ATG DRUG

1.5 mg/kg/day x 3 days (Days -3 to -1)

Flu/Cy/TBI

Eligibility Criteria

• Age: 1 Year - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Northside Hospital, Inc.: lead

Study Sites (2)

Blood and Marrow Transplant Group of Georgia

Atlanta, Georgia, 30342, United States

RECRUITING

Northside Hospital

Atlanta, Georgia, 30342, United States

RECRUITING

Related Publications (9)

• 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.

  PMID: 20018919 BACKGROUND

• 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.

  PMID: 24319167 RESULT

• 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.

  PMID: 24319166 RESULT

• 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.

  PMID: 22517900 RESULT

• 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, -C, -DRB1, and -DQB1 Allele-Matched Unrelated Donors and HLA-Identical Sibling Donors: A Multivariable Analysis Including Disease Risk Index. Biol Blood Marrow Transplant. 2016 Jan;22(1):125-33. doi: 10.1016/j.bbmt.2015.09.002. Epub 2015 Sep 7.

  PMID: 26359881 RESULT

• 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.

  PMID: 25797174 RESULT

• 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.

  PMID: 24842530 RESULT

• 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.

  PMID: 2889870 RESULT

• 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 Transplant. 2012 Dec;18(12):1876-82. doi: 10.1016/j.bbmt.2012.07.004. Epub 2012 Jul 11.

  PMID: 22796534 RESULT

MeSH Terms

Conditions

Anemia, Aplastic

Interventions

fludarabine; Cyclophosphamide; Whole-Body Irradiation; thymoglobulin

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Radiotherapy; Therapeutics; Investigative Techniques

Study Officials

• Melhem Solh, MD

  Blood and Marrow Transplant Group of Georgia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Melhem Solh, MD

CONTACT

404-255-1930; msolh@bmtga.com

Stacey Brown

CONTACT

404-851-8238; stacey.brown@northside.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2016
• First Posted: July 11, 2016
• Study Start: September 9, 2016
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2028
• Last Updated: April 20, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)