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

NCT02988466 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2016LS092MT2016-15
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

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

Conditions

Hematologic Malignancies

Keywords

Acute Leukemias; Acute myeloid leukemia (AML); Acute lymphoblastic leukemia (ALL)/lymphoma; Biphenotypic/Undifferentiated/Prolymphocytic Leukemias; Myelodysplastic syndrome; Chronic myelogenous leukemia; Minimal Residual Disease (MRD) positive leukemia; Leukemia or Myelodysplastic Syndromes (MDS) in aplasia; Myeloproliferative neoplasms/myelofibrosis; Relapsed large-cell lymphoma, mantle-cell lymphoma and Hodgkin lymphoma; Burkitt's lymphoma; Relapsed T-cell lymphoma; Natural Killer cell malignancies; Relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma, follicular lymphoma; Lymphoplasmacytic lymphoma; Relapsed multiple myeloma; Bone marrow failure syndromes

Outcome Measures

Primary Outcomes (1)

• Disease-free Survival (DFS)

  Percentage of participants that were disease-free survival (DFS) at 1 year post-transplant

  1 year

Secondary Outcomes (4)

• 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

Study Arms (4)

Arm A: Haplo-HCT <55 years old

EXPERIMENTAL

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; Drug: GVHD Prophylaxis

CLOSED Arm B: Haplo-HCT ≥55 years old

EXPERIMENTAL

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; Drug: GVHD Prophylaxis

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

EXPERIMENTAL

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; Biological: Haplo HCT ≥55 and < 65 years old

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

EXPERIMENTAL

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; Biological: Haplo HCT ≥65 and ≤75 years old

Interventions

Haplo HCT ≥55 years old BIOLOGICAL

* Fludarabine (Flu) * Cyclophosphamide (Cy) * Melphalan (Mel): Dose reduction by 30% * Total body irradiation (TBI) * Non-T-cell depleted donor bone marrow stem cell infusion

Also known as: HLA-haploidentical related hematopoietic cells transplant

CLOSED Arm B: Haplo-HCT ≥55 years old

GVHD Prophylaxis DRUG

* Cyclophosphamide (Cy) * Tacrolimus (Tac) * Mycophenolate mofetil (MMF)

Arm A: Haplo-HCT <55 years old; Arm C: Haplo-HCT HCT-CI ≤2 aged ≥55 and < 65yo; Arm D: Haplo-HCT aged ≥65 and ≤75yo OR any age HCT-CI ≥3; CLOSED Arm B: Haplo-HCT ≥55 years old

Haplo HCT ≥55 and < 65 years old BIOLOGICAL

* Fludarabine (Flu) * Cyclophosphamide (Cy) * Melphalan (Mel) * Total body irradiation (TBI) * non-T-cell depleted donor bone marrow stem cells

Also known as: HLA-haploidentical related hematopoietic cells transplant

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

Haplo HCT ≥65 and ≤75 years old BIOLOGICAL

* Fludarabine (Flu) * Cyclophosphamide (Cy) * Total body irradiation (TBI)

Also known as: HLA-haploidentical related hematopoietic cells transplant

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

Eligibility Criteria

• Age: Up to 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• \< 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.

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Hematologic Neoplasms; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Neoplasm, Residual; Leukemia; Myeloproliferative Disorders; Primary Myelofibrosis; Dendritic Cell Sarcoma, Interdigitating; Lymphoma, Mantle-Cell; Hodgkin Disease; Burkitt Lymphoma; Lymphoma, T-Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Follicular; Multiple Myeloma; Bone Marrow Failure Disorders

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Neoplasms by Histologic Type; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes; Histiocytic Disorders, Malignant; Histiocytosis; Lymphoma, Non-Hodgkin; Lymphoma; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Leukemia, B-Cell; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Results Point of Contact

• Title: Mark Juckett, MD
• Organization: University of Minnesota, Masonic Cancer Center

juck0001@umn.edu

(612) 626-5654

Study Officials

• Najla El Jurdi, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2016
• First Posted: December 9, 2016
• Study Start: January 24, 2017
• Primary Completion: May 2, 2023
• Study Completion: March 24, 2025
• Last Updated: May 28, 2025
• Results First Posted: May 28, 2025

Record last verified: 2025-05

Locations

US (1)