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

Primary Purpose

Severe Aplastic Anemia

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Fludarabine

Cyclophosphamide

Total Body Irradiation

Rabbit ATG

Cyclophosphamide

About this trial

This is an interventional treatment trial for Severe Aplastic Anemia focused on measuring SAA

Eligibility Criteria

1 Year - 75 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Blood and Marrow Transplant Group of GeorgiaRecruiting
Northside HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Flu/Cy/TBI

Arm Description

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

Outcomes

Primary Outcome Measures

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%.

Secondary Outcome Measures

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

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

Determine incidence of chronic GVHD at 6 months and 1 year post transplantation by assessing signs and symptoms of GVHD throughout post-transplant course

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

Full Information

NCT ID

NCT02828592

First Posted

July 6, 2016

Last Updated

October 19, 2022

Sponsor

Northside Hospital, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT02828592

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Recruiting

Study Start Date

September 9, 2016 (Actual)

Primary Completion Date

August 31, 2025 (Anticipated)

Study Completion Date

August 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Northside Hospital, Inc.

4. Oversight

Data Monitoring Committee

5. Study Description

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.

Detailed 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%.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Severe Aplastic Anemia

Keywords

SAA

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Flu/Cy/TBI

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Fludarabine

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Intervention Description

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

Intervention Type

Radiation

Intervention Name(s)

Total Body Irradiation

Other Intervention Name(s)

TBI

Intervention Description

300 cGy x1 dose (Day -1)

Intervention Type

Drug

Intervention Name(s)

Rabbit ATG

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Intervention Description

Post-transplant: 50 mg/kg IV QD (Day +3 to +4)

Primary Outcome Measure Information:

Title

Demonstrate sustained engraftment after T-cell replete HLA-mismatched haploidentical bone marrow transplantation by collecting chimerism tests monthly following transplant

Description

Hypothesis is that following preparative regimen and bone marrow transplantation, the 30-day graft failure rate will be <30%.

Time Frame

2 years

Secondary Outcome Measure Information:

Title

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

Time Frame

2 years

Title

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

Time Frame

2 years

Title

Determine incidence of chronic GVHD at 6 months and 1 year post transplantation by assessing signs and symptoms of GVHD throughout post-transplant course

Time Frame

2 years

Title

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

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

1 Year

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Melhem Solh, MD

Phone

404-255-1930

msolh@bmtga.com

First Name & Middle Initial & Last Name or Official Title & Degree

Stacey Brown

Phone

404-851-8238

stacey.brown@northside.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Melhem Solh, MD

Organizational Affiliation

Blood and Marrow Transplant Group of Georgia

Official's Role

Principal Investigator

Facility Information:

Facility Name

Blood and Marrow Transplant Group of Georgia

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30342

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Melhem Solh, MD

Phone

404-255-1930

msolh@bmtga.com

Facility Name

Northside Hospital

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30342

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Melhem Solh, MD

Phone

404-255-1930

msolh@bmtga.com

First Name & Middle Initial & Last Name & Degree

Stacey Brown

Phone

404-851-8238

stacey.brown@northside.com

First Name & Middle Initial & Last Name & Degree

Scott Solomon, MD

First Name & Middle Initial & Last Name & Degree

H. Kent Holland, MD

First Name & Middle Initial & Last Name & Degree

Asad Bashey, MD, PhD

First Name & Middle Initial & Last Name & Degree

Lawrence Morris, MD

First Name & Middle Initial & Last Name & Degree

Melhem Solh, MD

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

20018919

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.

Results Reference

background

PubMed Identifier

24319167

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.

Results Reference

result

PubMed Identifier

24319166

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.

Results Reference

result

PubMed Identifier

22517900

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.

Results Reference

result

PubMed Identifier

26359881

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, -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.

Results Reference

result

PubMed Identifier

25797174

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 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.

Results Reference

result

PubMed Identifier

24842530

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.2014.62. Epub 2014 May 19.

Results Reference

result

PubMed Identifier

2889870

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.

Results Reference

result

PubMed Identifier

22796534

Citation

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.

Results Reference

result

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

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