Transplantation of Partially Mismatched Related or Matched Unrelated Bone Marrow for Patients With Refractory Severe Aplastic Anemia

• Status: Active, not recruiting
• Trial end date: 2023-11-01
• Target enrollment: 0
• Participant gender: All

Summary

Our primary objective is to determine if it is feasible for SAA patients to be transplanted using non-myeloablative conditioning and post transplantation cyclophosphamide with partially HLA-mismatched donors.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Treatments: Cyclophosphamide; Fludarabine; Fludarabine phosphate; Mesna; Mycophenolate mofetil; Mycophenolic Acid; Tacrolimus; Thymoglobulin

Criteria

Inclusion Criteria:

• Patients with relapsed or refractory SAA or very SAA defined:

• Bone marrow (< 25% cellular)

• Peripheral cytopenias (at least 2 of 3)

• ANC < 500 per ml

• Platelets < 20,000 per ml

• Absolute retic < 60,000 or corrected retic < 1%

• Very severe: as above, but ANC < 200

• Disease may be designated as acquired or inherited if previous counts known (these other bone marrow failure disorders that are characterized by aplastic anemia may go by additional names such as dyskeratosis congenita or PNH)

• Failed at least one course of immunosuppressive therapy (if presumed acquired disease). Patients with inherited disease will be characterized as refractory and do not require immunosuppressive first.

• Age 0- upper age limit as determined by current institutional standards

• Good performance status (ECOG 0 or 1; Karnofsky and Lansky 70-100)

• Patients and donors must be able to sign consent forms (or if a minor the parent will sign). Donors should be willing to donate.

• Patients must be geographically accessible and willing to participate in all stages of treatment.

• Adequate end-organ function as measured by:

1. Left ventricular ejection fraction > or = to 35%, or shortening fraction > 25% (For pediatric patients, a normal ejection fraction is required)

2. Bilirubin ≤ 3.0 mg/dL (unless due to Gilbert's syndrome or hemolysis), and ALT and AST ≤ 5 x ULN

3. FEV1 and FVC > or = to 40% of predicted; or in pediatric patients, if unable to perform pulmonary function tests due to young age, oxygen saturation >92% on room air

Exclusion Criteria:

• Patients will not be excluded on the basis of sex, racial or ethnic background.

• Prior transfusions from selected donor (as this could have cause recipient alloimmunization against the donor)

• Women of childbearing potential who currently are pregnant (HCG+) or who are not practicing adequate contraception.

• Patients who have any debilitating medical or psychiatric illness that would preclude their giving informed consent or their receiving optimal treatment and follow up.

• Uncontrolled viral, bacterial, or fungal infections (HIV infection permitted if viral load undetectable)