NMA Haplo or MUD BMT for Newly Diagnosed Severe Aplastic Anemia

• Register: ClinicalTrials.gov
• Last refreshed on: 4 October 2021
• Main ID: NCT02833805
• Date of registration: 12/07/2016
• Prospective Registration: Yes
• Primary sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Public title: NMA Haplo or MUD BMT for Newly Diagnosed Severe Aplastic Anemia
• Scientific title: A Phase II Trial of Non-Myeloablative (NMA) Conditioning and Transplantation of Partially HLA-Mismatched/Haploidentical Related or Matched Unrelated Donor (MUD) Bone Marrow for Newly Diagnosed Patients With Severe Aplastic Anemia
• Date of first enrolment: September 2016
• Target sample size: 21
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02833805
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Amy E DeZern, MD
• Affiliation: Johns Hopkins University

Key inclusion & exclusion criteria

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.

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.



Age minimum: N/A
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Severe Aplastic Anemia

Immunosuppression

Bone Marrow Failure

Aplastic Anemia

Intervention(s)

Drug: Fludarabine

Drug: Mycophenolate mofetil

Drug: Cyclophosphamide

Radiation: Total body irradiation

Drug: Thymoglobulin

Drug: Tacrolimus

Primary Outcome(s)

Overall survival and engraftment at one year [Time Frame: 1 year]

Secondary Outcome(s)

Estimate transplant-related mortality [Time Frame: 1 year]

Incidence of primary graft failure [Time Frame: 1 year]

Incidence of grades III-IV acute GVHD, Day 100 [Time Frame: 1 year]

Incidence of secondary graft failure [Time Frame: 1 year]

Overall survival at one year [Time Frame: 1 year]

Incidence of grades II-IV acute GVHD, Day 100 [Time Frame: Day 100]

Estimate GVHD-free relapse-free survival (GRFS) [Time Frame: 1 year]

Probability of platelet recovery [Time Frame: 1 year]

Estimate full donor chimerism [Time Frame: Day 60]

Incidence of chronic GVHD, one year [Time Frame: 1 year]

Probability of neutrophil recovery [Time Frame: 1 year]

Secondary ID(s)

J1688

IRB00107139

Source(s) of Monetary Support

Please refer to primary and secondary sponsors