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

Sponsor

Masonic Cancer Center, University of Minnesota (Other)

Overall Status

Recruiting

CT.gov ID

NCT02988466

Collaborator

(none)

Enrollment

Location

Arms

82.2

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief 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)

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

Condition or Disease	Intervention/Treatment	Phase
Hematologic Malignancies	Biological: Haplo HCT <55 years old 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	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

84 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Reduced Intensity (RIC) Conditioning And Transplantation of HLA-Haploidentical Related Hematopoietic Cells (Haplo-HCT) For Patients With Hematologic Malignancies

Actual Study Start Date :

Jan 24, 2017

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A: Haplo-HCT <55 years old 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	Biological: Haplo HCT <55 years old Fludarabine (Flu) Cyclophosphamide (Cy) Melphalan (Mel) Total body irradiation (TBI) Non-T-cell depleted donor bone marrow stem cell infusion Day 0 Other Names: HLA-haploidentical related hematopoietic cells transplant Drug: GVHD Prophylaxis Cyclophosphamide (Cy) Tacrolimus (Tac) Mycophenolate mofetil (MMF)
Experimental: CLOSED Arm B: Haplo-HCT ≥55 years old 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.	Biological: Haplo HCT ≥55 years old Fludarabine (Flu) Cyclophosphamide (Cy) Melphalan (Mel): Dose reduction by 30% Total body irradiation (TBI) Non-T-cell depleted donor bone marrow stem cell infusion Other Names: HLA-haploidentical related hematopoietic cells transplant Drug: GVHD Prophylaxis Cyclophosphamide (Cy) Tacrolimus (Tac) Mycophenolate mofetil (MMF)
Experimental: Arm C: Haplo-HCT HCT-CI ≤2 aged ≥55 and < 65yo 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.	Drug: GVHD Prophylaxis Cyclophosphamide (Cy) Tacrolimus (Tac) Mycophenolate mofetil (MMF) Biological: Haplo HCT ≥55 and < 65 years old Fludarabine (Flu) Cyclophosphamide (Cy) Melphalan (Mel) Total body irradiation (TBI) non-T-cell depleted donor bone marrow stem cells Other Names: HLA-haploidentical related hematopoietic cells transplant
Experimental: Arm D: Haplo-HCT aged ≥65 and ≤75yo OR any age HCT-CI ≥3 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.	Drug: GVHD Prophylaxis Cyclophosphamide (Cy) Tacrolimus (Tac) Mycophenolate mofetil (MMF) Biological: Haplo HCT ≥65 and ≤75 years old Fludarabine (Flu) Cyclophosphamide (Cy) Total body irradiation (TBI) Other Names: HLA-haploidentical related hematopoietic cells transplant

Outcome Measures

Primary Outcome Measures

Disease-free survival (DFS) [1 year]
estimate disease-free survival (DFS) at 1 year post-transplant

Secondary Outcome Measures

Incidence of grade II-IV and grade III-IV acute graft versus-host-disease (GVHD) [day 100]
Treatment related mortality (TRM) [6 month, 1 and 2 year]
Relapse incidence [1 and 2 year]
Incidence of serious fungal and viral infection [at day 100 and 1 year]
post-HCT

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 75 Years

Sexes Eligible for Study:

All

Accepts 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.