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

NCT02790515 | Active Not Recruiting Phase 2 FDA Drug FDA Device

• 2 other identifiers: REF2HCTNCI-2016-00812
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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)

Outcome Measures

Primary Outcomes (1)

• The number of patients engrafted by day +30 post-transplant

  ANC engraftment is defined as the first of 3 consecutive tests performed on different days of an ANC ≥ 500/mm\^3 with evidence of donor cell engraftment.

  30 days post-transplant

Secondary Outcomes (4)

• The number of patients experiencing Blinatumomab permanent discontinuation due to toxicity

  3 months post-transplant

• The estimate of cumulative incidence of relapse

  One year post-transplant

• The cumulative incidence of acute and chronic Graft-Versus-Host Disease (GVHD)

  One year post transplant

• The cumulative incidence of transplant related mortality

  100 days post transplant

Study Arms (1)

Treatment

EXPERIMENTAL

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.

Drug: Anti-thymocyte globulin (rabbit); Drug: Blinatumomab; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: G-CSF; Drug: Melphalan; Drug: Mesna; Drug: Rituximab; Drug: Tacrolimus; Drug: Thiotepa; Biological: HPC,A Infusion; Device: CliniMACS; Drug: Sirolimus

Interventions

Anti-thymocyte globulin (rabbit) DRUG

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

Also known as: Thymoglobulin®, rabbit ATG

Treatment

Blinatumomab DRUG

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

Also known as: Blincyto

Treatment

Cyclophosphamide DRUG

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

Also known as: Cytoxan

Treatment

Fludarabine DRUG

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

Also known as: Fludara

Treatment

G-CSF DRUG

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

Also known as: Filgrastim, Neupogen®

Treatment

Melphalan DRUG

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

Also known as: L-phenylalanine mustard, Phenylalanine mustard, L-PAM, L-sarcolysin, Alkeran

Treatment

Mesna DRUG

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

Also known as: Mesnex

Treatment

Rituximab DRUG

Given IV prior to transplant on Day -1.

Also known as: Rituxan™

Treatment

Tacrolimus 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.

Also known as: FK506, Prograf®, Protopic®

Treatment

Thiotepa DRUG

Given IV prior to transplant on Day -3.

Also known as: Thioplex® by Immunex, TESPA, TSPA

Treatment

HPC,A Infusion 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.

Also known as: Transplant

Treatment

CliniMACS 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.

Also known as: Cell Selection System

Treatment

Sirolimus 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.

Also known as: Rapamycin, Rapamune®

Treatment

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Sarcoma, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myelomonocytic, Juvenile; Myelodysplastic Syndromes; Lymphoma, Non-Hodgkin

Interventions

Antilymphocyte Serum; thymoglobulin; blinatumomab; Cyclophosphamide; fludarabine; fludarabine phosphate; Granulocyte Colony-Stimulating Factor; Filgrastim; Melphalan; Mesna; Rituximab; Tacrolimus; Thiotepa; Transplantation; Sirolimus

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Sarcoma; Neoplasms, Connective and Soft Tissue; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Myelodysplastic-Myeloproliferative Diseases; Lymphoma

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Macrolides; Lactones; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Surgical Procedures, Operative

Study Officials

• Brandon Triplett, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2016
• First Posted: June 6, 2016
• Study Start: July 14, 2016
• Primary Completion: July 1, 2025
• Study Completion (Estimated): July 1, 2026
• Last Updated: August 12, 2025

Record last verified: 2025-08

Locations

US (1)