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

Phase 2

Active, not recruiting

• Conditions: Hematologic Malignancies
• Interventions: 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

• Registration Number: NCT02988466
• Lead Sponsor: Masonic Cancer Center, University of Minnesota

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) \>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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-12-07
• Study First Submitted QC: 2016-12-08
• Study First Posted: 2016-12-09
• Study Start: 2017-01-24
• Primary Completion: 2023-05-02
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-13
• Last Update Posted: 2024-08-14
• Study Completion: 2024-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 78

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A: Haplo-HCT <55 years old	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
Arm A: Haplo-HCT <55 years old	GVHD Prophylaxis	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
CLOSED Arm B: Haplo-HCT ≥55 years old	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.
CLOSED Arm B: Haplo-HCT ≥55 years old	GVHD Prophylaxis	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.
Arm C: Haplo-HCT HCT-CI ≤2 aged ≥55 and < 65yo	GVHD Prophylaxis	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.
Arm C: Haplo-HCT HCT-CI ≤2 aged ≥55 and < 65yo	Haplo HCT ≥55 and < 65 years old	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.
Arm D: Haplo-HCT aged ≥65 and ≤75yo OR any age HCT-CI ≥3	GVHD Prophylaxis	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.
Arm D: Haplo-HCT aged ≥65 and ≤75yo OR any age HCT-CI ≥3	Haplo HCT ≥65 and ≤75 years old	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.

Primary Outcome Measures

Name	Time	Method
Disease-free survival (DFS)	1 year	estimate disease-free survival (DFS) at 1 year post-transplant

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Masonic Cancer Center at University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States