Protocol Summary

Protocol No.: OCR15213

Sponsor Protocol No.: 15-MMUD

Study Title
A Multi-Center, Phase II Trial of HLA-Mismatched Unrelated Donor Bone Marrow Transplantation with Post-Transplantation Cyclophosphamide for Patients with Hematologic Malignancies

Principal Investigator(s)
Norkin, Maxim

This is a multi-center, single arm Phase II study of hematopoietic cell transplantation (HCT) using human leukocyte antigen (HLA)-mismatched unrelated bone marrow transplantation donors and post-transplantation cyclophosphamide (PTCy), sirolimus and mycophenolate mofetil (MMF) for graft versus host disease (GVHD) prophylaxis in patients with hematologic malignancies.

Phase: Phase II

Age Group: Both

Scope: National

Regimen A (RIC: Flu/Cy/TBI): Fludarabine, Cyclophosphamide, Total Body Irradiation and Infusion of non-T-cell depleted bone marrow on Day 0

Regimen B 2a (FIC: Bu/Cy): Busulfan, Cyclophosphamide, and Infusion of non-T-cell depleted bone marrow on Day 0

Regimen B 2b (FIC: Bu/Flu): Busulfan, Fludarabine, and Infusion of non-T-cell depleted bone marrow on Day 0

Regimen C (FIC: Cy/TBI): Cyclophosphamide, Total Body Irradiation, and Infusion of non-T-cell depleted bone marrow on Day 0

All arms: Post-HCT Cyclophosphamide 50mg/kg IV on Day+3, +4

Detailed Eligibility
1. Age >= 15 years and 2. Partially HLA-mismatched unrelated donor: HLA typing will be performed at high resolution (allele level) for the HLA-A, -B, -C, and -DRB1 loci; a minimum match of 4/8 at HLA-A, -B, -C, and -DRB1 is required
3. Product planned for infusion is bone marrow
4. Disease and disease status:
- Acute Leukemias or T lymphoblastic lymphoma in 1st or subsequent complete remission (CR): Acute lymphoblastic leukemia (ALL)/T lymphoblastic lymphoma; acute myelogenous leukemia (AML); acute biphenotypic leukemia (ABL); acute undifferentiated leukemia (AUL)
- Myelodysplastic Syndrome (MDS), fulfilling the following criteria: Subjects with de novo MDS who have or have previously had Intermediate-2 or High risk disease as determined by the International Prognostic Scoring System (IPSS). Current Intermediate-2 or High risk disease is not a requirement; Subjects must have - Chronic Lymphocytic Leukemia (CLL) in CR if RIC is to be used; in CR or partial response (PR) if FIC is to be used
- Chemotherapy-sensitive lymphoma in status other than 1st CR
5. Performance status: Karnofsky or Lansky score ≥ 60% (Appendix A)
6. Adequate organ function defined as:
- Cardiac: left ventricular ejection fraction (LVEF) at rest ≥ 35% (RIC cohort) or LVEF at rest ≥ 40% (FIC cohort), or left ventricular shortening fraction (LVFS) ≥ 25%
- Pulmonary: diffusing capacity of the lungs for carbon monoxide (DLCO), forced expiratory volume (FEV1), forced vital capacity (FVC) ≥ 50% predicted by pulmonary function tests (PFTs)
- Hepatic: total bilirubin ≤ 2.5 mg/dL, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) - Renal: serum creatinine (SCr) within normal range for age (see table 2.3). If SCr is outside normal range for age, creatinine clearance (CrCl) > 40 mL/min/1.73m2 must be obtained (measured by 24-hour (hr) urine specimen or nuclear glomerular filtration rate (GFR), or calculated GFR (by Cockcroft-Gault formula for those aged ≥ 18 years; by Original Schwartz estimate for those 7. Subjects ≥ 18 years of age must have the ability to give informed consent according to applicable regulatory and local institutional requirements. Legal guardian permission must be obtained for subjects 8. Subjects with documentation of confirmed HIV-1 infection (i.e. HIV-positive), and a hematologic malignancy who meets all other eligibility requirements must:
- Receive only RIC regimen (i.e. Regimen A)
- Be willing to comply with effective antiretroviral therapy (ARV)
- Have achieved a sustained virologic response for 12 weeks after cessation of hepatitis C antiviral treatment (in HIV-positive subjects with hepatitis C)

1. HLA-matched related or 8/8 allele matched (HLA-A, -B, -C, -DRB1) unrelated donor available. This exclusion does not apply to HIV-positive subjects who have a CCR5delta32 homozygous donor.
2. Autologous HCT 3. Females who are breast-feeding or pregnant
4. HIV-positive subjects:

**Contact Study Team for complete eligibility details

Applicable Disease Sites
Stem Cell Transplant

Participating Institutions
UF Gainesville

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