Reduced Intensity (RIC) Conditioning And Transplantation of HLA-Haplo-HCT
Hematologic Malignancies
About this trial
This is an interventional treatment trial for Hematologic Malignancies focused on measuring 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
Eligibility 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)
- 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.
Sites / Locations
- Masonic Cancer Center at University of Minnesota
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Experimental
Experimental
Arm A: Haplo-HCT <55 years old
CLOSED Arm B: 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
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
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.
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.
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.