This trial has been completed.

Conditions 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)
Treatments cyclophosphamide, fludarabine, g-csf, interleukin-2, melphalan, thiotepa, rituximab, natural killer cell therapy, t-cell depleted hpc transplant, cd45ra-depleted hpc transplant
Phase phase 2
Target CD20
Sponsor St. Jude Children's Research Hospital
Start date October 2014
End date April 2015
Trial size 12 participants
Trial identifier NCT02259348, NCI-2014-01925, REFNK1


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.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Participants undergo a conditioning regimen with cyclophosphamide, fludarabine, aldesleukin (interleukin-2), natural killer cell therapy, anti-thymocyte globulin, rituximab, thiotepa, and melphalan prior to transplantation of T-cell depleted HPC transplant on day 0 and CD45RA-depleted HPC transplant on day 1. Beginning Day 6 post-transplant, patients receive G-CSF daily until ANC recovers to normal level.
cyclophosphamide Cytoxan
Given intravenously (IV)
fludarabine Fludara
Given IV
g-csf Filgrastim
Given IV or subcutaneously (SQ)
interleukin-2 IL-2
Given SQ
melphalan L-phenylalanine mustard
Given IV
thiotepa ThioplexV
Given IV
rituximab Rituxan™
Given IV
natural killer cell therapy NK cell therapy
Given IV
t-cell depleted hpc transplant HPC,A Infusion(ɑ/β T cell depleted)
T-cell depleted hematopoietic stem cells will be infused on day 0.
cd45ra-depleted hpc transplant
CD45RA depleted stem cells will be infused on day 1.

Primary Outcomes

Percentage of Participants Engrafted by Day 42 Post-transplant
time frame: Day 42 post transplantation

Secondary Outcomes

Incidence of Malignant Relapse
time frame: one year post transplantation
Event-free Survival (EFS)
time frame: one year post transplantation
Overall Survival (OS)
time frame: one year post transplantation
Incidence and Severity of Acute GvHD
time frame: 100 days post transplantation
Incidence and Severity of Chronic GvHD
time frame: one year post transplantation
Rate of Transplant-related Mortality (TRM)
time frame: 100 days post transplantation

Eligibility Criteria

Male or female participants up to 21 years old.

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.

Additional Information

Official title CD45A-Depleted Haploidentical Hematopoietic Progenitor Cell and Natural Killer Cell Transplantation for Hematologic Malignancies Relapsed or Refractory Despite Prior Transplantation
Principal investigator Brandon Triplett, MD
Description PRIMARY OBJECTIVE: - To estimate engraftment by day +42 post-transplant in patients who receive CD45RA-depleted haploidentical donor progenitor cell transplantation following reduced intensity conditioning regimen that includes haploidentical natural killer (NK) cells. SECONDARY OBJECTIVES: - Estimate the incidence of malignant relapse, event-free survival, and overall survival at one-year post-transplantation. - Estimate incidence and severity of acute and chronic (GvHD). - Estimate the rate of transplant related mortality (TRM) in the first 100 days after transplantation. Blood progenitor cells will be collected from adult donors to be used for transplantation. Donor cells will be processed and filtered in a laboratory at St. Jude using a machine called the CliniMACS™ device, and later infused (transplanted) into the participant through his/her veins. Participants undergo a conditioning regimen beginning Day 21 prior to progenitor cell transplantation that includes chemotherapy medications and natural killer cells in preparation for transplantation. They will then receive T-cell depleted HPC transplant followed by CD45RA-depleted HPC transplant the following day.
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by St. Jude Children's Research Hospital.
Location data was received from the National Cancer Institute and was last updated in September 2016.