Repeat Transplantation for Relapsed or Refractory Hematologic Malignancies Following Prior Transplantation
Condition: Acute Lymphoblastic Leukemia (ALL); Acute Myeloid Leukemia (AML); Myeloid Sarcoma; Chronic Myelogenous Leukemia (CML); Juvenile Myelomonocytic Leukemia (JMML); Myelodysplastic Syndrome (MDS); Non-Hodgkin Lymphoma (NHL)
MeSH terms: Leukemia; Leukemia, Myeloid, Acute; Neoplasms; Lymphoma, Non-Hodgkin; Preleukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Hematologic Neoplasms; Leukemia, Myelomonocytic, Juvenile; Sarcoma, Myeloid; Myelodysplastic Syndromes
Intervention: Cyclophosphamide; Fludarabine; G-CSF; Interleukin-2; Melphalan; Thiotepa; Rituximab; Natural killer cell therapy; T-cell depleted HPC transplant; CD45RA-depleted HPC transplant
Intervention description: Given intravenously (IV); Given IV; Given IV or subcutaneously (SQ); Given SQ; Given IV; Given IV; Given IV; Given IV; T-cell depleted hematopoietic stem cells will be infused on day 0.; CD45RA depleted stem cells will be infused on day 1.
Intervention MeSH terms: Aldesleukin; Cyclophosphamide; Melphalan; Mechlorethamine; Thiotepa; Rituximab; Fludarabine; Fludarabine phosphate; Interleukin-2
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Maximum age: 21 Years
Healthy volunteers: No
Keywords: Hematological malignancies; Allogeneic hematopoietic cell transplant; Refractory hematologic malignancy; Relapsed hematologic malignancy

Summary:

      This pilot phase II trial studies how well a new reduced intensity conditioning regimen that
      includes haploidentical donor NK cells followed by the infusion of selectively T-cell
      depleted progenitor cell grafts work in treating younger patients with hematologic
      malignancies that have returned after or did not respond to treatment with a prior
      transplant. Giving chemotherapy and natural killer cells before a donor progenitor cell
      transplant may help stop the growth of cells in the bone marrow, including normal
      blood-forming cells (progenitor cells) and cancer cells. It may also stop the patient's
      immune system from rejecting the donor's cells. When the healthy progenitor cells from a
      related donor are infused into the patient they make red blood cells, white blood cells, and
      platelets. Sometimes the transplanted cells from a donor can make an immune response against
      the body's normal cells (called graft-versus-host disease). Removing specific T cells from
      the donor cells before the transplant may prevent this.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age less than or equal to 21 years.

          -  One of the following hematologic malignancies that has relapsed or remains refractory
             after prior allogeneic hematopoietic cell transplant (HCT):

               -  ALL, AML, Myeloid Sarcoma, CML, Juvenile myelomonocytic leukemia (JMML),
                  myelodysplastic syndrome (MDS), 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 in CNS complete
             remission (CR)

          -  Does not have current uncontrolled bacterial, fungal, or viral infection.

          -  Patient must fulfill pre-transplant evaluation:

          -  Left ventricular ejection fraction > 40%, or shortening fraction ≥ 25%.

          -  Creatinine clearance (CrCl) or glomerular filtration rate (GFR) ≥ 50 ml/min/1.73m2.

          -  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 (See Appendix A).

          -  Bilirubin ≤ 3 times the upper limit of normal for age.

          -  Alanine aminotransferase (ALT) ≤ 5 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

          -  DONOR: At least single haplotype matched (≥ 3 of 6) family member

          -  DONOR: At least 18 years of age.

          -  DONOR: HIV negative.

          -  DONOR: Not pregnant as confirmed by negative serum or urine pregnancy test within 14
             days prior to enrollment (if female).

          -  DONOR: Not breast feeding.

          -  DONOR: Regarding donation eligibility, is identified as either:

               -  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.