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

NCT ID: NCT02790515

Last Updated: 2025-08-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

170 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-07-14

Study Completion Date

2026-07-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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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)

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment

Participants receive a conditioning regimen of antithymocyte globulin (rabbit), cyclophosphamide, mesna, fludarabine, thiotepa, tacrolimus (first 5 participants enrolled), sirolimus (used beginning with 6th enrolled participant), melphalan, rituximab. This is followed by HPC,A infusion (transplant), then by G-CSF and blinatumomab.

Cells for infusion are prepared using the CliniMACS System.

Group Type EXPERIMENTAL

Anti-thymocyte globulin (rabbit)

Intervention Type DRUG

Given intravenous (IV) prior to transplant on Days -14, -13, -12.

Blinatumomab

Intervention Type DRUG

Given by continuous IV infusion at least 2 weeks post-engraftment. Blinatumomab will be given only to patients with CD19+ malignancies.

Cyclophosphamide

Intervention Type DRUG

Given by IV infusion prior to transplant on Day -9.

Fludarabine

Intervention Type DRUG

Given IV prior to transplant on Days -8, -7, -6, -5, and -4.

G-CSF

Intervention Type DRUG

Given IV or subcutaneous (SQ) following transplant on Days 6 and 7.

Melphalan

Intervention Type DRUG

Given IV prior to transplant on Days -2 and -1.

Mesna

Intervention Type DRUG

Given IV prior to cyclophosphamide administration and at approximately 3, 6, and 9 hours after cyclophosphamide infusion.

Rituximab

Intervention Type DRUG

Given IV prior to transplant on Day -1.

Tacrolimus

Intervention Type DRUG

Given oral (PO) or IV beginning prior to transplant on Day -2. The dose will begin to taper at approximately day +60 after transplant in the absence of GVHD. Tacrolimus was used for the first 5 participants enrolled on study. Subsequent participants receive sirolimus.

Thiotepa

Intervention Type DRUG

Given IV prior to transplant on Day -3.

HPC,A Infusion

Intervention Type BIOLOGICAL

Hematopoietic Progenitor Cell, Apheresis (HPC,A) infusion of TCRɑβ+ depleted cells on day of transplant (Day 0) and HPC,A infusion of CD45RA+ depleted cells on Day +1 following transplant.

CliniMACS

Intervention Type DEVICE

The mechanism of action of the CliniMACS Cell Selection System is based on magnetic-activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can then be separated in a magnetic field using an immunomagnetic label specific for the cell type of interest, such as CD3+ human T cells.

Sirolimus

Intervention Type DRUG

Given orally (PO) starting Day 0. The dose will be tapered off over two weeks starting on Day +42 in the absence of GVHD.

Interventions

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Anti-thymocyte globulin (rabbit)

Given intravenous (IV) prior to transplant on Days -14, -13, -12.

Intervention Type DRUG

Blinatumomab

Given by continuous IV infusion at least 2 weeks post-engraftment. Blinatumomab will be given only to patients with CD19+ malignancies.

Intervention Type DRUG

Cyclophosphamide

Given by IV infusion prior to transplant on Day -9.

Intervention Type DRUG

Fludarabine

Given IV prior to transplant on Days -8, -7, -6, -5, and -4.

Intervention Type DRUG

G-CSF

Given IV or subcutaneous (SQ) following transplant on Days 6 and 7.

Intervention Type DRUG

Melphalan

Given IV prior to transplant on Days -2 and -1.

Intervention Type DRUG

Mesna

Given IV prior to cyclophosphamide administration and at approximately 3, 6, and 9 hours after cyclophosphamide infusion.

Intervention Type DRUG

Rituximab

Given IV prior to transplant on Day -1.

Intervention Type DRUG

Tacrolimus

Given oral (PO) or IV beginning prior to transplant on Day -2. The dose will begin to taper at approximately day +60 after transplant in the absence of GVHD. Tacrolimus was used for the first 5 participants enrolled on study. Subsequent participants receive sirolimus.

Intervention Type DRUG

Thiotepa

Given IV prior to transplant on Day -3.

Intervention Type DRUG

HPC,A Infusion

Hematopoietic Progenitor Cell, Apheresis (HPC,A) infusion of TCRɑβ+ depleted cells on day of transplant (Day 0) and HPC,A infusion of CD45RA+ depleted cells on Day +1 following transplant.

Intervention Type BIOLOGICAL

CliniMACS

The mechanism of action of the CliniMACS Cell Selection System is based on magnetic-activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can then be separated in a magnetic field using an immunomagnetic label specific for the cell type of interest, such as CD3+ human T cells.

Intervention Type DEVICE

Sirolimus

Given orally (PO) starting Day 0. The dose will be tapered off over two weeks starting on Day +42 in the absence of GVHD.

Intervention Type DRUG

Other Intervention Names

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Thymoglobulin® rabbit ATG Blincyto Cytoxan Fludara Filgrastim Neupogen® L-phenylalanine mustard Phenylalanine mustard L-PAM L-sarcolysin Alkeran Mesnex Rituxan™ FK506 Prograf® Protopic® Thioplex® by Immunex TESPA TSPA Transplant Cell Selection System Rapamycin Rapamune®

Eligibility Criteria

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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


* 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.
Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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St. Jude Children's Research Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Brandon Triplett, MD

Role: PRINCIPAL_INVESTIGATOR

St. Jude Children's Research Hospital

Locations

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St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status

Countries

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United States

Related Links

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http://www.stjude.org

St. Jude Children's Research Hospital

http://www.stjude.org/protocols

Clinical Trials Open at St. Jude

Other Identifiers

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NCI-2016-00812

Identifier Type: REGISTRY

Identifier Source: secondary_id

REF2HCT

Identifier Type: -

Identifier Source: org_study_id

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