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

University of Minnesota (UMN)

Status and phase: Active, not recruiting; Phase 2

Conditions: Hematologic Malignancies

Treatments: Biological: Haplo HCT <55 years old; Drug: GVHD Prophylaxis; Biological: Haplo HCT ≥55 and < 65 years old; Biological: Haplo HCT ≥65 and ≤75 years old; Biological: Haplo HCT ≥55 years old

Study type: Interventional

Funder types: Other

Identifiers

NCT02988466

2016LS092

MT2016-15 (Other Identifier)

Details and patient eligibility

About

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

Enrollment: 78 patients

Sex: All

Ages: Under 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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78 participants in 4 patient groups

Arm A: Haplo-HCT <55 years old

Experimental group

Description:

Reduced-intensity conditioning and transplantation of human leukocyte antigen (HLA) -haploidentical related donor stem cells for patients \<55 years old with hematopoietic cell transplantation Comorbidity Index (HCT-CI) ≤2

Treatment:

Drug: GVHD Prophylaxis

Biological: Haplo HCT <55 years old

CLOSED Arm B: Haplo-HCT ≥55 years old

Experimental group

Description:

Reduced-intensity conditioning and transplantation of human leukocyte antigen (HLA) -haploidentical related donor stem cells for patients ≥55 years old or younger with hematopoietic cell transplantation Comorbidity Index (HCT-CI) ≥3.

Treatment:

Biological: Haplo HCT ≥55 years old

Drug: GVHD Prophylaxis

Arm C: Haplo-HCT HCT-CI ≤2 aged ≥55 and < 65yo

Experimental group

Description:

Reduced-intensity conditioning and transplantation of human leukocyte antigen (HLA) -haploidentical related donor stem cells for patients with hematopoietic cell transplantation Comorbidity Index (HCT-CI) ≤2 aged ≥55 and \< 65 years old.

Treatment:

Biological: Haplo HCT ≥55 and < 65 years old

Drug: GVHD Prophylaxis

Arm D: Haplo-HCT aged ≥65 and ≤75yo OR any age HCT-CI ≥3

Experimental group

Description:

Reduced-intensity conditioning and transplantation of human leukocyte antigen (HLA) -haploidentical related donor stem cells for patients patients ≥65 and ≤75 years old OR any age group with hematopoietic cell transplantation Comorbidity Index (HCT-CI) ≥3.

Treatment:

Biological: Haplo HCT ≥65 and ≤75 years old

Drug: GVHD Prophylaxis