Severe Aplastic AnemiaPhase 2NCT02828592
Haploidentical Bone Marrow Transplant With Post-Transplant Cyclophosphamide for Patients With Severe Aplastic Anemia
A Phase 2 study testing Fludarabine, Cyclophosphamide and Total Body Irradiation in people with Severe Aplastic Anemia, run by Northside Hospital, Inc. at 2 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 1 year to 75 years
- Conditions the study is for
- Severe Aplastic Anemia
- What is being tested?
- Fludarabine, Cyclophosphamide and Total Body Irradiation
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 2 sitesUnited States
- Study dates
- 9 Sep 2016to 31 Aug 2028
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Show all 11Show fewer
- <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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
Blood and Marrow Transplant Group of Georgia
Atlanta, Georgia, 30342
Melhem Solh, MD, 404-255-1930, msolh@bmtga.com
- Recruiting
Northside Hospital
Atlanta, Georgia, 30342
Melhem Solh, MD, 404-255-1930, msolh@bmtga.com
Stacey Brown, 404-851-8238, stacey.brown@northside.com
About this study
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
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.
Read the 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%.
- Conditions
- Severe Aplastic Anemia
- Being tested
- Fludarabine, Cyclophosphamide, Total Body Irradiation, Rabbit ATG
- Keywords
- SAA
- Medical subject headings
- Anemia, Aplastic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FludarabineDrug
30 mg/m2 IV QD x 5 days (Days -6 to -2)
CyclophosphamideDrug
14.5 mg/kg/day IV x 2 doses (Days -6 \& -5)
Total Body IrradiationRadiation
Also called TBI
300 cGy x1 dose (Day -1)
Rabbit ATGDrug
1.5 mg/kg/day x 3 days (Days -3 to -1)
CyclophosphamideDrug
Post-transplant: 50 mg/kg IV QD (Day +3 to +4)
| Study group | Role | What they receive |
|---|---|---|
| Flu/Cy/TBI | Experimental | Fludarabine, Cyclophosphamide, TBI followed by bone marrow transplantation. Post-transplant Cyclophosphamide will be on Days 3 \& 4. Receives: Drug: Fludarabine; Drug: Cyclophosphamide; Radiation: Total Body Irradiation; Drug: Rabbit ATG |
What is being measured
The primary outcome is the main question the study is designed to answer.
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%.
Measured: 2 years
Secondary outcomes (4)
Determine the incidence of regimen-related mortality at 100 days post transplantation by recording treatment-related adverse events
Measured: 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
Measured: 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
Measured: 2 years
Estimate overall survival at 100 days and 1 year post transplantation by collecting survival information at those time points
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2016 (estimated)
- Study start9 Sep 2016
- Primary completion31 Aug 2027 (estimated)
- Study completion31 Aug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Severe Aplastic AnemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Northside Hospital, Inc.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Melhem Solh, MD, Principal investigator, Blood and Marrow Transplant Group of Georgia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02828592
- Sponsor's protocol ID
- NSH 1158
- Status last verified
- Oct 2026
- First submitted
- 6 Jul 2016
- Last updated
- 14 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 20018919Socie 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.
PubMed 24319167Young 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.
PubMed 24319166Scheinberg 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.
PubMed 22517900Bashey 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.
PubMed 26359881Solomon 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.
PubMed 25797174Bashey 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.
PubMed 24842530Rozman 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.
PubMed 2889870Atta 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.
PubMed 22796534