Provision of TCRγδ T Cells and Memory T Cells Plus Selected Use of Blinatumomab in Naïve T-cell Depleted Haploidentical Donor Hematopoietic Cell Transplantation for Hematologic Malignancies Relapsed or Refractory Despite Prior Transplantation

  • STATUS
    Recruiting
  • End date
    Jul 1, 2025
  • participants needed
    52
  • sponsor
    St. Jude Children's Research Hospital
Updated on 4 October 2022
cancer
graft versus host disease
fludarabine
hematologic malignancy
tacrolimus
cyclophosphamide
lymphoma
hodgkin's disease
rituximab
filgrastim
ejection fraction
granulocyte colony stimulating factor
melphalan
cell transplantation
leukemia
transplant conditioning
thiotepa
antithymocyte globulin
colony stimulating factor
myelomonocytic leukemia
mesna
juvenile myelomonocytic leukemia

Summary

This study seeks to examine treatment therapy that will reduced regimen-related toxicity and relapse while promoting rapid immune reconstitution with limited serious graft-versus-host-disease (GVHD) and also improve disease-free survival and quality of life. The investigators propose to evaluate the safety and efficacy of selective naive T-cell depleted (by TCRɑβ and CD45RA depletion, respectively) haploidentical hematopoietic cell transplant (HCT) following reduced intensity conditioning regimen that avoids radiation in patients with hematologic malignancies that have relapsed or are refractory following prior allogeneic transplantation.

PRIMARY OBJECTIVE:

  • To estimate engraftment by day +30 post-transplant in patients who receive TCRɑβ-depleted and CD45RA-depleted haploidentical donor progenitor cell transplantation following reduced intensity conditioning regimen without radiation.

SECONDARY OBJECTIVES:

  • Assess the safety and feasibility of the addition of Blinatumomab in the early post-engraftment period in patients with CD19+ malignancy.
  • 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.

Description

Blood progenitor cells will be obtained from a partially matched adult family member (donor). After processing and filtration using the CliniMACS device, cells will be infused into participants meeting eligibility criteria.

Prior to transplant, participants will receive a conditioning treatment of rabbit ATG, cyclophosphamide, fludarabine, thiotepa, melphalan, and rituximab. Mesna will be given to help prevent side effects of cyclophosphamide. Tacrolimus will be given to help reduce the risk of GVHD. G-CSF will be given after transplant to help the donor progenitor cells make white blood cells faster so that the immune system is better able to fight infection.

Blood progenitor cells will be given in two infusions on Day 0 and Day +1. Progenitor cells then move through the blood stream to the bone marrow space where they should begin to grow. Participant blood will be monitored for 100 days to assure that the progenitor cells begin to grow. If the growth is low, additional progenitor cells may be given.

Blood tests will be monitored for up to one year to observe how well the donor cells grow and their effect on the infection-fighting system.

Details
Condition Acute Lymphoblastic Leukemia (ALL), Acute Myeloid Leukemia (AML), Myeloid Sarcoma, Chronic Myeloid Leukemia (CML), Juvenile Myelomonocytic Leukemia (JMML), Myelodysplastic Syndrome (MDS), Non-Hodgkin Lymphoma (NHL)
Treatment Rituximab, G-CSF, cyclophosphamide, melphalan, Fludarabine, Tacrolimus, MESNA, Sirolimus, thiotepa, Blinatumomab, CliniMACs, HPC,A Infusion, Anti-thymocyte globulin (rabbit)
Clinical Study IdentifierNCT02790515
SponsorSt. Jude Children's Research Hospital
Last Modified on4 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Age less than or equal to 21 years
Any of the following hematologic malignancies that has relapsed or remains refractory after prior allogeneic HCT (this includes any stage of disease - such as refractory due to induction failure, refractory in relapse, or in any CR - as long as the hematologic malignancy remained persistent or returned after a previous allogeneic 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 CNS leukemia, it must be treated and in CNS CR
Does not have current uncontrolled bacterial, fungal, or viral infection
There is no minimum time from the previous transplant, but patients must meet the following criteria
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) or aspartate aminotransferase (AST) ≤ 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
Inclusion Criteria for Haploidentical Donor
At least single haplotype matched (≥ 3 of 6) family member
At least 18 years of age
HIV negative
Not pregnant as confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment (if female)
Not breast feeding
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
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