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

• Status: Terminated
• Trial end date: 2015-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: St. Jude Children's Research Hospital
• Collaborator: Assisi Foundation
• Treatments: Antilymphocyte Serum; Antineoplastic Agents; Busulfan; Clofarabine; Cyclophosphamide; Cytarabine; Immunosuppressive Agents; JM 3100; Mycophenolate mofetil; Mycophenolic Acid; Plerixafor; Tacrolimus; Thymoglobulin

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.