NMA Haplo or MUD BMT for Newly Diagnosed Severe Aplastic Anemia

NCT02833805 | Completed Phase 2 Results

• 2 other identifiers: J1688IRB00107139
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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.

Conditions

Severe Aplastic Anemia; Aplastic Anemia; Bone Marrow Failure; Immunosuppression

Keywords

immunosuppression; nonmyeloablative; non-myeloablative; allogeneic; tacrolimus; bone marrow; bone marrow transplant; cyclophosphamide; thymoglobulin; ATG; fludarabine

Outcome Measures

Primary Outcomes (1)

• Overall Survival and Engraftment at One Year

  Number of enrolled participants who receive BMT, achieve engraftment, and are alive at one year post bone marrow transplant (BMT).

  1 year

Secondary Outcomes (11)

• Overall Survival at One Year

  1 year

• Probability of Neutrophil Recovery as Assessed by the Number of Participants Who Have Recovered Neutrophil Counts

  1 year

• Probability of Platelet Recovery as Assessed by Number of Participants Who Have Recovered Platelet Counts

  1 year

• Number of Participants Who Experience Primary Graft Failure

  1 year

• Number of Participants Who Experience Secondary Graft Failure

  1 year

Study Arms (1)

Bone marrow transplant

EXPERIMENTAL

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.

Drug: Thymoglobulin; Drug: Fludarabine; Drug: Cyclophosphamide; Radiation: Total body irradiation; Drug: Tacrolimus; Drug: Mycophenolate mofetil

Interventions

Thymoglobulin DRUG

Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily

Also known as: Anti-thymocyte globulin, ATG

Bone marrow transplant

Fludarabine DRUG

Days -6 through -2: 30 mg/m\^2 IV daily

Also known as: Fludara

Bone marrow transplant

Cyclophosphamide DRUG

Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily

Also known as: Cytoxan, Cy, CTX

Bone marrow transplant

Total body irradiation RADIATION

Day -1: 200 centigray (cGy) in a single fraction

Also known as: TBI

Bone marrow transplant

Tacrolimus DRUG

Start on Day 5 through Day 365

Also known as: FK-506, FK506, Prograf

Bone marrow transplant

Mycophenolate mofetil DRUG

Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)

Also known as: MMF, CellCept

Bone marrow transplant

Eligibility Criteria

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

You may qualify if:

• Confirmed diagnosis of inherited or acquired severe aplastic anemia (SAA)
• One of the following available donors:
• HLA-haploidentical relative
• If recipient is \>= 40 years old, may use HLA-matched related donor
• 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%

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

Related Publications (2)

• DeZern AE, Zahurak M, Symons HJ, Cooke KR, Huff CA, Jain T, Swinnen LJ, Imus PH, Wagner-Johnston ND, Ambinder RF, Levis M, Luznik L, Bolanos-Meade J, Fuchs EJ, Jones RJ, Brodsky RA. Alternative donor BMT with posttransplant cyclophosphamide as initial therapy for acquired severe aplastic anemia. Blood. 2023 Jun 22;141(25):3031-3038. doi: 10.1182/blood.2023020435.

  PMID: 37084383 DERIVED

• DeZern AE, Zahurak ML, Symons HJ, Cooke KR, Rosner GL, Gladstone DE, Huff CA, Swinnen LJ, Imus P, Borrello I, Wagner-Johnston N, Ambinder RF, Luznik L, Bolanos-Meade J, Fuchs EJ, Jones RJ, Brodsky RA. Haploidentical BMT for severe aplastic anemia with intensive GVHD prophylaxis including posttransplant cyclophosphamide. Blood Adv. 2020 Apr 28;4(8):1770-1779. doi: 10.1182/bloodadvances.2020001729.

  PMID: 32343796 DERIVED

MeSH Terms

Conditions

Anemia, Aplastic; Bone Marrow Failure Disorders

Interventions

thymoglobulin; Antilymphocyte Serum; fludarabine; fludarabine phosphate; Cyclophosphamide; Whole-Body Irradiation; Tacrolimus; Mycophenolic Acid

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Radiotherapy; Therapeutics; Investigative Techniques; Macrolides; Lactones; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Results Point of Contact

• Title: Dr. Amy DeZern
• Organization: Johns Hopkins University

adezerb1@jhmi.edu

410-502-7208

Study Officials

• Amy E DeZern, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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 12, 2016
• First Posted: July 14, 2016
• Study Start: September 1, 2016
• Primary Completion: July 1, 2021
• Study Completion: July 1, 2021
• Last Updated: July 12, 2022
• Results First Posted: July 12, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)