NMA Haplo or MUD BMT for Newly Diagnosed Severe Aplastic Anemia

Phase 2

Completed

• Conditions: Bone Marrow Failure; Aplastic Anemia; Immunosuppression; Severe Aplastic Anemia
• Interventions: Drug: Thymoglobulin; Drug: Fludarabine; Drug: Cyclophosphamide; Radiation: Total body irradiation; Drug: Tacrolimus; Drug: Mycophenolate mofetil

• Registration Number: NCT02833805
• Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary

Our primary objective is to determine if it is feasible for previously untreated severe aplastic anemia (SAA) patients to be transplanted using non-myeloablative conditioning and post transplantation cyclophosphamide.

Detailed Description

This is a clinical trial of upfront bone marrow transplantation for patients with SAA who do not have a fully human leukocyte antigen (HLA) matched donor. The trial uses a conditioning regimen which has been successful in the refractory and relapsed setting to maximize engraftment and post transplant therapy to minimize graft versus host disease (GVHD). This would be used here in patients who have not yet undergone immunosuppressive therapy for their SAA or are thought to be unlikely to respond to immunosuppressive therapy for SAA.

Study Timeline

• Study First Submitted: 2016-07-12
• Study First Submitted QC: 2016-07-13
• Study First Posted: 2016-07-14
• Study Start: 2016-09
• Primary Completion: 2021-07
• Study Completion: 2021-07
• Results First Submitted: 2022-05-05
• Status Verified: 2022-06
• Results First Submitted QC: 2022-06-16
• Last Update Submitted: 2022-06-16
• Results First Posted: 2022-07-12
• Last Update Posted: 2022-07-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

Inclusion Criteria

• Confirmed diagnosis of inherited or acquired severe aplastic anemia (SAA)

• One of the following available donors:

  1. HLA-haploidentical relative
  2. If recipient is >= 40 years old, may use HLA-matched related donor
  3. For recipients with inherited bone marrow failure syndromes (IBMFS) with clear evidence of same disorder in potential related donors, may use 10/10 matched unrelated donor

• Recipient and/or legal guardian must sign protocol informed consent

• Donor must be willing to donate bone marrow

• Left ventricular ejection fraction (LVEF) >= 40%. For recipients < 13 years old, shortening fraction >= 26% may be used instead.

• Bilirubin < 3 x upper limit of normal (ULN) for age, unless patient has Gilbert's disease

• aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 5 x ULN for age

• For patients >= 13 years old: estimated creatinine clearance > 50 mL/min using Cockcroft-Gault formula and actual body weight

• For patients >= 1 but < 13 years old: glomerular filtration rate (GFR) estimated by updated Schwartz formula >= 90 mL/min/1.73 m^2. If estimated GFR is < 90 mL/min/1.73 m^2, 24-hour measured creatinine clearance must be > 50 mL/min/1.73 m^2.

• For patients >= 8 years old, diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) > 40%; forced expiratory volume at one second (FEV1) > 50%; forced vital capacity (FVC) > 50%

• For patients < 8 years old or unable to undergo pulmonary function testing: no evidence of dyspnea at rest; no need for supplemental oxygen; oxygen saturation > 92% on room air

• Karnofsky/Lansky status (depending on age) >= 70%

• Females and males of childbearing potential must agree to practice 2 effective methods of contraception at the same time. If unwilling, they must agree to complete abstinence.

Read More

Exclusion Criteria

• Previous administration of immunosuppressive therapy for SAA.
• Fanconi anemia. At minimum, this diagnosis must be excluded by diepoxybutane (DEB) or equivalent testing on peripheral blood or marrow in patients < 30 years old.
• Clonal cytogenetic abnormalities consistent with pre-myelodysplastic syndrome (pre-MDS) or MDS on bone marrow examination
• Presence of anti-donor antibodies
• Prior allogeneic stem cell transplant
• Prior solid organ transplant
• Uncontrolled bacterial, viral, or fungal infection
• HIV seropositivity
• Active hepatitis B or C infection determined by serology and/or nucleic acid testing (NAT)
• Pregnancy or active breastfeeding
• Prior malignancies except: resected basal carcinoma or treated cervical carcinoma in situ; cancer treated with curative intent > 5 years previously. Other prior cancers will not be allowed unless approved by the PI.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Bone marrow transplant	Cyclophosphamide	Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis.
Bone marrow transplant	Total body irradiation	Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis.
Bone marrow transplant	Thymoglobulin	Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis.
Bone marrow transplant	Fludarabine	Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis.
Bone marrow transplant	Tacrolimus	Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis.
Bone marrow transplant	Mycophenolate mofetil	Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis.

Primary Outcome Measures

Name	Time	Method
Overall Survival and Engraftment at One Year	1 year	Number of enrolled participants who receive BMT, achieve engraftment, and are alive at one year post bone marrow transplant (BMT).

Secondary Outcome Measures

Name	Time	Method
Overall Survival at One Year	1 year	Number of participants alive at one year after BMT.
Number of Participants Who Experience Chronic GVHD	2 years	Number of participants who experience chronic GVHD by two years after BMT.
Probability of Platelet Recovery as Assessed by Number of Participants Who Have Recovered Platelet Counts	1 year	Probability of platelet recovery will be assessed by the number of participants who have recovered platelet counts at 1 year.
Number of Participants Who Experience Primary Graft Failure	1 year	Number of participants who experience primary graft failure by one year after BMT.
Number of Participants Who Experience Grades II-IV Acute GVHD	Day 100	Number of participants who experience grade II, III, or IV acute GVHD by Day 100.
Transplant-related Mortality	1 year	Number of participants deceased for reasons related to BMT at 1 year.
Probability of Neutrophil Recovery as Assessed by the Number of Participants Who Have Recovered Neutrophil Counts	1 year	Probability of neutrophil recovery will be assessed by the number of participants who have recovered neutrophil counts at 1 year (\>500 ANC).
GVHD-free Relapse-free Survival (GRFS)	1 year	Number of participants alive, without relapse, and without GVHD at 1 year.
Number of Participants With Full Donor Chimerism	Day 60	Number of participants with full donor chimerism at Day 60.
Number of Participants Who Experience Secondary Graft Failure	1 year	Number of participants who experience secondary graft failure by one year after BMT.
Number of Participants Who Experience Grades III-IV Acute GVHD	Day 100	Number of participants who experience grade III or IV acute GVHD by Day 100.

Trial Locations

Locations (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; 🇺🇸 Baltimore, Maryland, United States