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Reduced Intensity (RIC) Conditioning And Transplantation of HLA-Haploidentical Related Hematopoietic

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ClinicalTrials.gov Identifier: NCT02988466
Recruitment Status : Recruiting
First Posted : December 9, 2016
Last Update Posted : January 16, 2019
Sponsor:
Information provided by (Responsible Party):
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 44 patients, using 22 patients separately for arms A and B.

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

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : January 24, 2017
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : January 2021


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 Name: 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 Name: 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 Name: 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 Name: HLA-haploidentical related hematopoietic cells transplant




Primary Outcome Measures :
  1. Disease-free survival (DFS) [ Time Frame: 1 year ]
    estimate disease-free survival (DFS) at 1 year post-transplant


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



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Ages Eligible for Study:   up to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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)

Exclusion Criteria:

  • < 70 years with an available 5-6/6 HLA-A, B, DRB1 matched sibling donor
  • Pregnancy or breastfeeding
  • Evidence of HIV infection or known HIV positive serology
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02988466


Contacts
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Contact: Timothy Krepski 612-273-2800 tkrepsk1@fairview.org

Locations
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United States, Minnesota
Masonic Cancer Center at University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Tim Krepski    612-273-2800    tkrepsk1@fairview.org   
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
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Principal Investigator: Claudio Brunstein, MD, PhD Masonic Cancer Center, University of Minnesota
Principal Investigator: Najla El Jurdi, MD Masonic Cancer Center, University of Minnesota

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Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT02988466     History of Changes
Other Study ID Numbers: 2016LS092
MT2016-15 ( Other Identifier: University of Minnesota Blood and Marrow Transplant Program )
First Posted: December 9, 2016    Key Record Dates
Last Update Posted: January 16, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Masonic Cancer Center, University of Minnesota:
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

Additional relevant MeSH terms:
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Neoplasms