Donor Stem Cell Transplantation Using α/β+ T-lymphocyte Depleted Grafts From HLA Mismatched Donors

NCT03615105 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: 18-224
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being done to learn whether a new method to prevent rejection between the donor immune system and the patient's body is effective.

Conditions

Acute Lymphoid Leukemia (ALL); Acute Myeloid Leukemia (AML); Chronic Myeloid Leukemia (CML); Hodgkin Lymphoma; Non-Hodgkin Lymphoma; Chronic Lymphocytic Leukemia

Keywords

Allogeneic Hematopoietic Cell Transplantation; α/β+ T-lymphocyte; 18-224

Outcome Measures

Primary Outcomes (1)

• the Number of Incidences of Grade 3-4 Acute GVHD

  The intervention will be considered unpromising if the rate of GVHD is greater than 40% and promising if the rate is 20% or less. Number of participants with and without SAE will be evaluated.

  2 years

Study Arms (3)

Radiation, Thiotepa & Cyclophosphamide

EXPERIMENTAL

Radiation: Hyperfractionated total body irradiation; Drug: Thiotepa; Drug: Cyclophosphamide; Procedure: HPC(A) stem cell allograft; Drug: Rituximab; Device: Rabbit antithymocyte globulin

Busulfan, Fludarabine & Melphalan

EXPERIMENTAL

Drug: Busulfan; Drug: Fludarabine; Drug: Melphalan; Procedure: HPC(A) stem cell allograft; Drug: Rituximab; Device: Rabbit antithymocyte globulin

Clofarabine, Thiotepa & Melphalan

EXPERIMENTAL

Drug: Thiotepa; Drug: Melphalan; Drug: Clofarabine; Procedure: HPC(A) stem cell allograft; Drug: Rituximab; Device: Rabbit antithymocyte globulin

Interventions

Hyperfractionated total body irradiation RADIATION

Hyperfractionated TBI is administered by a linear accelerator at a dose rate of \<20 cGy/minute. Doses of 125 cGy/fraction are administered at a minimum interval of 4 hours between fractions, three times/day for a total of 11 or 12 doses (1,375 or 1,500 cGy) over 4 days (days -9 through -6).

Radiation, Thiotepa & Cyclophosphamide

Thiotepa DRUG

Thiotepa 5 mg/kg IV

Clofarabine, Thiotepa & Melphalan; Radiation, Thiotepa & Cyclophosphamide

Cyclophosphamide DRUG

Cyclophosphamide 60 mg/kg IV

Radiation, Thiotepa & Cyclophosphamide

Busulfan DRUG

Busulfan (adult/ped dose)

Busulfan, Fludarabine & Melphalan

Fludarabine DRUG

Fludarabine 25 mg/m2 IV

Busulfan, Fludarabine & Melphalan

Melphalan DRUG

Melphalan 70 mg/m2 IV

Busulfan, Fludarabine & Melphalan; Clofarabine, Thiotepa & Melphalan

Clofarabine DRUG

Clofarabine 20-30 mg/m2 IV

Clofarabine, Thiotepa & Melphalan

HPC(A) stem cell allograft PROCEDURE

All patients will receive anti-thymocyte globulin based conditioning followed by a G-CSF mobilized, peripheral blood hematopoietic progenitor cell HPC(A) product depleted of TCR-α/β+ Tlymphocytes using the CliniMACS system.

Busulfan, Fludarabine & Melphalan; Clofarabine, Thiotepa & Melphalan; Radiation, Thiotepa & Cyclophosphamide

Rituximab DRUG

Rituximab 200 mg IV flat dose

Busulfan, Fludarabine & Melphalan; Clofarabine, Thiotepa & Melphalan; Radiation, Thiotepa & Cyclophosphamide

Rabbit antithymocyte globulin DEVICE

Rabbit antithymocyte globulin dosing per nomogram. This dynamic nomogram is based on absolute lymphocyte count at the start of conditioning and can result in either 2 or 3 day ATG administration. If a patient requires 2 day administration the subjequent chemotherapies may be moved forward by one day at the treating physician's discretion.

Busulfan, Fludarabine & Melphalan; Clofarabine, Thiotepa & Melphalan; Radiation, Thiotepa & Cyclophosphamide

Eligibility Criteria

• Age: Up to 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with any of the following hematologic malignancies who are considered to be eligible for allogeneic transplantation:
• Acute lymphoid leukemia (ALL) in first complete remission (CR1) with high risk for relapse including:
• Detectable minimal residual disease by either multicolor flow cytometry or by genomic assay after initial induction therapy
• t(9;22) or detected BCR-ABL1 translocation by genomic methodologies
• BCR-ABL1-Like B-ALL \[23\] including mutations of IKZF1 or CRLF2
• Translocations or mutations involving 11q23 (MLL) gene.
• Hypodiploid karyotype
• Deletion of 9p
• Loss of 17p or TP53 mutation
• T-lymphocyte lineage antigen expression (T-ALL)
• Prior CNS or other extramedullary involvement
• WBC count ≥ 100,000 cells/μL at diagnosis
• Acute biphenotypic or bilineal leukemia in CR1
• Acute myeloid leukemia (AML) in CR1 with
• Detectable minimal residual disease (MRD) by either multicolor flow cytometry or by genomic assay after initial induction therapy

You may not qualify if:

• Persons with a HLA matched sibling donor or a 8/8 allele level HLA-matched unrelated donor.
• Female patients who are pregnant or breast-feeding.
• Persons with an infection that is not responding to antimicrobial therapy.
• Persons who are seropositive for HIV.
• Persons with active/detectable central nervous system malignancy.
• Persons who do not meet the age and organ function criteria specified above.
• Presence of psychiatric or neurologic disease, or lack of social support that limits the patient's ability to comply with the treatment protocol including supportive care, followup, and research tests.
• Prior allogeneic hematopoietic cell transplantation are ineligible.
• Patients with history of other malignancy within 5 years of study therapy are ineligible with the following exceptions: Low grade prostate cancer (Gleason's ≤6) treated with curative intent, breast ductal carcinoma in situ treated with curative intent, or nonmelanomatous skin carcinomas.
• Partially HLA-matched unrelated volunteers (allele level matched at 6-7 of 8 HLA loci: -A, -B, -C, and -DRB1) are eligible.
• Related, haploidentical donors are eligible.
• Able to provide informed consent to the donation process
• Meet standard criteria for donor collection as defined by the National Marrow Donor Program Guidelines.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Hodgkin Disease; Lymphoma, Non-Hodgkin; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Thiotepa; Cyclophosphamide; Busulfan; fludarabine; Melphalan; Clofarabine; Rituximab

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; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma; Leukemia, B-Cell

Intervention Hierarchy (Ancestors)

Phosphoramides; Organophosphorus Compounds; Organic Chemicals; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Brian Shaffer, MD
• Organization: Memorial Sloan Kettering Cancer Center

shaffeb1@mskcc.org

646-608-3737

Study Officials

• Brian Shaffer, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will receive one of three myeloablative conditioning regimens followed by a Alpha/beta+ T-cell depleted peripheral blood stem cell product and short course tacrolimus. Donors are HLA mismatched unrelated adults or haploidentical family members.

Study Record Dates

• First Submitted: July 30, 2018
• First Posted: August 3, 2018
• Study Start: July 25, 2018
• Primary Completion: March 6, 2024
• Study Completion: March 6, 2024
• Last Updated: April 6, 2025
• Results First Posted: April 6, 2025

Record last verified: 2024-03

Locations

US (1)