Clinical trial NCT02988466: Reduced Intensity (RIC) Conditioning And Transplantation of HLA-Haplo-HCT
Official title: Reduced Intensity (RIC) Conditioning And Transplantation of HLA-Haploidentical Related Hematopoietic Cells (Haplo-HCT) For Patients With Hematologic Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2016-12-09
Enrollment: 78
Sex: ALL
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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.

Primary outcomes:
measure: Disease-free Survival (DFS)
timeFrame: 1 year
Secondary outcomes:
measure: Incidence of Grade II-IV and Grade III-IV Acute Graft Versus-host-disease (GVHD)
timeFrame: day 100
measure: Treatment Related Mortality (TRM)
timeFrame: 6 month, 1 and 2 year
measure: Relapse Incidence
timeFrame: 1 and 2 year
measure: Incidence of Serious Fungal and Viral Infection
timeFrame: at day 100 and 1 year
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Masonic Cancer Center at University of Minnesota
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Najla El Jurdi, MD
role: PRINCIPAL_INVESTIGATOR
References: