T-Cell Replete Haploidentical Donor Hematopoietic Stem Cell Plus Natural Killer (NK) Cell Transplantation in Patients With Hematologic Malignancies Relapsed or Refractory Despite Previous Allogeneic Transplant
Condition: Acute Lymphoblastic Leukemia; Acute Myelocytic Leukemia; Chronic Myelocytic Leukemia; Juvenile Myelomonocytic Leukemia; Myelodysplastic Syndrome; Hodgkin or Non-Hodgkin Lymphoma; Sarcoma, Myeloid
MeSH terms: Leukemia; Neoplasms; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Hematologic Neoplasms; Leukemia, Myelomonocytic, Juvenile; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Sarcoma, Myeloid; Myelodysplastic Syndromes
Intervention: clofarabine; cytarabine; busulfan; Plerixafor; cyclophosphamide; antithymocyte globulin (rabbit); stem cells; Tacrolimus; mycophenolate mofetil
Intervention description: Given on Day -9 and Day -8 (Day 0 is first stem cell infusion). Drug class: antineoplastic agent; Given on Day -9 and Day -8 (Day 0 is first stem cell infusion). Drug class: antineoplastic agent; Given on Day -7 and Day -6 (Day 0 is first stem cell infusion). Drug class: antineoplastic agent; Given on Day -7 and Day -6 (Day 0 is first stem cell infusion). Drug class: Hematopoietic Stem Cell Mobilizer; Given on Day -5 and Day +4 (Day 0 is first stem cell infusion). Drug class: antineoplastic agent; immunosuppressive agent.; Given on Day -4, Day -3, Day -2, and Day -1 (Day 0 is first stem cell infusion). Drug class: immunosuppressive agent.; Patients undergo T cell replete Hematopoietic stem cell infusion on Day 0 and Day +1. Patients undergo natural killer (NK) cell transplantation on day +6 (Day 0 is first stem cell infusion).; Given on Day +11 (Day 0 is first stem cell infusion). Drug class: immunosuppressive agent.; Given on Day +11 (Day 0 is first stem cell infusion). Drug class: immunosuppressive agent.
Intervention MeSH terms: Cytarabine; Plerixafor; Mycophenolic Acid; Cyclophosphamide; Busulfan; Clofarabine; Tacrolimus; Thymoglobulin; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: All
Maximum age: 21 Years
Healthy volunteers: No
Keywords: Hematologic malignancy; Hematopoietic cell transplant

Summary:

      The primary aim of this protocol is to evaluate if the one-year survival is significantly
      improved in the group of patients who receive a T-cell replete haploidentical donor
      hematopoietic cell transplant (HCT) with a novel reduced intensity conditioning regimen.
      Study population will consist of patients (21 years or under) with hematologic malignancies
      that have relapsed or are refractory after prior allogeneic transplant. Toxicity will be
      evaluated by the rate of transplant related mortality and the rates of moderate and severe
      graft-versus-host disease (GvHD) at day 100. The investigators will describe event-free, and
      disease-free survival at one year, as well as the rates of hematopoietic recovery and donor
      engraftment and study comprehensively immune reconstitution following T-cell replete
      haploidentical transplantation.
    

Eligibility criteria:

        Inclusion Criteria - for transplant recipient:

          -  Age less than 21 years.

          -  One of the following hematologic malignancies that has relapsed or remains refractory
             after prior allogeneic HCT:

               -  Acute lymphoblastic leukemia (ALL)

               -  Acute myeloid leukemia (AML) (including myeloid sarcoma)

               -  Chronic myelogenous leukemia (CML), juvenile myelomonocytic leukemia (JMML),
                  myelodysplastic syndrome (MDS), Hodgkin or non-Hodgkin lymphoma (NHL)

          -  Has a suitable single haplotype matched (≥ 3 of 6) family member donor.

          -  Does not have any other active malignancy other than the one for which this transplant
             is indicated.

          -  If prior central nervous system (CNS) leukemia, it must be treated and have no
             evidence of CNS disease

          -  Does not have current uncontrolled bacterial, fungal, or viral infection per the
             judgment of the principal investigator.

          -  Patient must fulfill pre-transplant evaluation:

               -  Left ventricular ejection fraction greater than 40%, or shortening fraction
                  greater than or equal to 25%.

               -  Creatinine clearance or Glomerular Filtration Rate of ≥70 ml/min/1.73m^2.

               -  Forced vital capacity (FVC) ≥ 40% of predicted value; or pulse oximetry ≥ 92% on
                  room air if patient is unable to perform pulmonary function testing.

               -  Karnofsky or Lansky (age-dependent) performance score ≥ 50.

               -  Total bilirubin ≤ 1.5 times the upper limit of normal for age.

               -  Alanine aminotransferase (ALT) ≤ 3 times the upper limit of normal for age.

               -  Not pregnant. If female with child bearing potential, must be confirmed by
                  negative serum or urine pregnancy test within 14 days prior to enrollment.

               -  Not breast feeding.

               -  Does not have active acute bronchiolitis obliterans or bronchiolitis obliterans
                  organizing pneumonia.

        Inclusion Criteria - for donor:

          -  At least single haplotype matched (≥ 3 of 6) family member,

          -  At least 18 years of age.

          -  Human immunodeficiency virus (HIV) negative.

          -  Not pregnant as confirmed by negative serum or urine pregnancy test within 14 days
             prior to enrollment (if female).

          -  Not breast feeding.

          -  A suitable donor is identified as either:

               -  Has completed the process of donor eligibility determination as outlined in 21
                  CFR 1271 and agency guidance; OR

               -  Does not meet 21 CFR 1271 eligibility requirements, but has a declaration of
                  urgent medical need completed by the principal investigator or physician
                  sub-investigator per 21 CFR 1271.

        Exclusion Criteria:

          -  Does not meet above inclusion criteria.