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

May 13, 2025 updated by: Masonic Cancer Center, University of Minnesota

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

78

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Masonic Cancer Center at University of Minnesota

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 75 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.
Drug: GVHD Prophylaxis
  • Cyclophosphamide (Cy)
  • Tacrolimus (Tac)
  • Mycophenolate mofetil (MMF)
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
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease-free Survival (DFS)
Time Frame: 1 year
Percentage of participants that were disease-free survival (DFS) at 1 year post-transplant
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Grade II-IV and Grade III-IV Acute Graft Versus-host-disease (GVHD)
Time Frame: day 100
Percentage of participants with incidence of grade II-IV and grade III-IV acute graft versus-host-disease (GVHD).
day 100
Treatment Related Mortality (TRM)
Time Frame: 6 month, 1 and 2 year
Percentage of participants experiencing treatment related mortality (TRM).
6 month, 1 and 2 year
Relapse Incidence
Time Frame: 1 and 2 year
Percentage of participants experiencing a relapse incidence at 1 and 2 years.
1 and 2 year
Incidence of Serious Fungal and Viral Infection
Time Frame: at day 100 and 1 year
Percentage of participants experiencing incidence of serious fungal and viral infection post-HCT
at day 100 and 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Masonic Cancer Center, University of Minnesota

Investigators

  • Principal Investigator: Najla El Jurdi, MD, Masonic Cancer Center, University of Minnesota

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 24, 2017

Primary Completion (Actual)

May 2, 2023

Study Completion (Actual)

March 24, 2025

Study Registration Dates

First Submitted

December 7, 2016

First Submitted That Met QC Criteria

December 8, 2016

First Posted (Estimated)

December 9, 2016

Study Record Updates

Last Update Posted (Actual)

May 28, 2025

Last Update Submitted That Met QC Criteria

May 13, 2025

Last Verified

May 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2016LS092
  • MT2016-15 (Other Identifier: University of Minnesota Blood and Marrow Transplant Program)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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