Reduced Intensity (RIC) Conditioning And Transplantation of HLA-Haplo-HCT

• Status: Recruiting
• Trial end date: 2022-01-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a single institution phase II study of a reduced intensity conditioning (RIC) followed by a haploidentical hematopoietic cell transplant (haplo-HCT) in persons with diagnosis of hematologic malignancy. Conditioning will consists of fludarabine, cyclophosphamide, melphalan and total body irradiation (TBI) preparative regimen with a melphalan dose reduction for patients ≥55 years old and those with HCT Comorbidity Index (CI) >3. This study uses a two-stage phase II design with accrual goal of 84 patients, using 28 patients separately for arms A, C and D

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

Details

• Lead Sponsor: Masonic Cancer Center, University of Minnesota

Criteria

Inclusion Criteria:

• Karnofsky performance status of ≥70% or Lansky play score ≥ 70%

• A related haploidentical bone marrow donor with up to 2 or 3 HLA locus-mismatches

• The donor and recipient must be HLA identical for at least one haplotype (using high resolution DNA based typing) at the following genetic loci: HLA-A, HLA-B, HLA-C, and HLA-DRB1.

• Adequate liver and renal function

• Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction ≥ 40%

• Diffusion capacity corrected (DLCOcorr) > 40% predicted, and absence of O2 requirements

• > 6 months after prior autologous transplant (if applicable)

• Agrees to use contraception during study treatment

• Voluntary written consent (adult or parent/guardian with presentation of the minor information sheet, if appropriate)

• Patients who are HIV+ must have undetectable viral load. All HIV+ patients must be evaluated by Infectious Disease (ID) and a HIV management plan establish prior to transplantation

Exclusion Criteria:

• < 70 years with an available 5-6/6 HLA-A, B, DRB1 matched sibling donor

• Pregnancy or breastfeeding

• Current active and uncontrolled serious infection

• Acute leukemia in morphologic relapse/persistent disease defined as > 5% blasts in normocellular bone marrow OR any % blasts if blasts have unique morphologic markers (e.g. Auer rods).

• CML in blast crisis

• Large cell lymphoma, mantle cell lymphoma and Hodgkin disease that is progressive on salvage therapy.

• stable non-bulky disease is acceptable.

• Active central nervous system malignancy

Criteria For Donor Selection:

• Donors must be HLA-haploidentical relatives of the patient, defined as having a shared HLA haplotype between donor and patient at HLA-A, -B, -C, and -DRB1.

• Eligible donors (14-70 years old) include biological children, siblings or half siblings, or parents, able and willing to undergo bone marrow harvesting.

• For donors <18 years, the maximum recipient weight (actual body weight) should not exceed 1.25 times the donor weight (actual body weight)1 In addition, bone marrow product volume should be limited to 20 ml/kg donor weight for donors <18 years.