TCR Alpha Beta T-cell and CD19 B-cell Depleted Peripheral Blood Stem Cell Transplantation Using the CliniMACS System for Patients With Non-Malignant Hematologic Disorders From Matched or Mismatched, Related or Unrelated Donors

NCT03615144 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: 17-596
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to find out if removing a specific type of white blood cell (called alpha beta T-cell) that help make up the transplant donor's stem cells can improve results of blood stem cell transplant for the participant's disease.

Conditions

Non-Malignant Hematologic Disorders

Keywords

T-cell; B-cell; CliniMACS System; Melphalan; Thiotepa; Clofarabine; Fludarabine; 17-596

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  Overall survival is defined as time from transplant to death or last follow-up. Rate greater than 0.75 would be considered a success.

  2 years

Study Arms (2)

Melphalan/Thiotepa/Clofarabine

ACTIVE COMPARATOR

Melphalan 70 mg/m2/day x 2, Thiotepa 7.5 mg/kg/day x 2 and Clofarabine 20-30 mg/m2/day x 5. Patients will also receive rabbit anti-thymocyte globulin at 2.5 mg/kg/day x 3 doses prior to the start of conditioning.

Drug: Melphalan; Drug: Thiotepa; Drug: Clofarabine; Drug: Anti-Thymocyte Globulin (Rabbit) (Thymoglobulin®); Procedure: CliniMACS reagents

Melphalan/Thiotepa/ Fludarabine

ACTIVE COMPARATOR

Melphalan 70 mg/m2/day x 2, Thiotepa 7.5 mg/kg/day x 2 and Fludarabine 30 mg/m2/day x 5. Patients will also receive rabbit anti-thymocyte globulin at 2.5 mg/kg/day x 3 doses prior to the start of conditioning.

Drug: Melphalan; Drug: Thiotepa; Drug: Fludarabine; Drug: Anti-Thymocyte Globulin (Rabbit) (Thymoglobulin®); Procedure: CliniMACS reagents

Interventions

Melphalan DRUG

Melphalan 70 mg/m2/day x 2

Melphalan/Thiotepa/ Fludarabine; Melphalan/Thiotepa/Clofarabine

Thiotepa DRUG

Thiotepa 7.5 mg/kg/day x 2

Melphalan/Thiotepa/ Fludarabine; Melphalan/Thiotepa/Clofarabine

Clofarabine DRUG

Clofarabine 20-30 mg/m2/day x 5

Melphalan/Thiotepa/Clofarabine

Fludarabine DRUG

Fludarabine 30 mg/m2/day x 5

Melphalan/Thiotepa/ Fludarabine

Anti-Thymocyte Globulin (Rabbit) (Thymoglobulin®) DRUG

antithymocyte globulin (ATG) (rabbit ATG 2.5 mg/kg/day x 3 or equine ATG 15 mg/kg/day x 3 (or 40 mg/kg/day x 1 equine ATG if rabbit ATG is not tolerated) during pre-transplant conditioning to deplete host T-cells that could hamper engraftment.

Melphalan/Thiotepa/ Fludarabine; Melphalan/Thiotepa/Clofarabine

CliniMACS reagents PROCEDURE

Products will then undergo TCR-αβ+ and CD-19 depletion using the CliniMACS.

Melphalan/Thiotepa/ Fludarabine; Melphalan/Thiotepa/Clofarabine

Eligibility Criteria

• Age: 1 Year - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Lethal disorders of Hematopoiesis correctable by transplant for which Alpha βeta T-cell and CD-19 depleted allogeneic hematopoietic stem cell transplantation is indicated including:
• Sickle cell disease (HbSS, HbSC, HbSB0 thalassemia, HbSB+, HbSD, HbSE) with at least one of the following criteria (Walters et al):
• Cerebrovascular accident lasting longer than 24 hours
• Impaired neuropsychological function with abnormal brain MRI/MRA
• Recurrent hospitalizations (\>2 episodes/year over several years) or exchange transfusions for acute chest syndrome
• Recurrent priapism
• Stage I or II sickle chronic lung disease
• Sickle cell nephropathy (moderate to severe proteinuria or glomerular filtration rate 30-50% of predicted normal value for age)
• Bilateral proliferative retinopathy with major visual impairment in at least one eye
• Osteonecrosis of multiple joints
• Red cell alloimmunization during chronic transfusion therapy
• Thalassemia major with at least one of the following criteria:
• Age \<16 years
• Available HLA-identical sibling
• Red blood cell transfusion dependency

You may not qualify if:

• Female patients who are pregnant or breast-feeding
• Active viral, bacterial or fungal infection
• Patient seropositive for HIV-I/II; HTLV-I/II
• Karnofsky (adult)/Lansky (pediatric) \< 70%
• Inherited DNA repair deficiency: Fanconi Anemia and Dyskeratosis Congenita. These are presently undergoing transplantation based on a multi-center protocol
• Patients with Thalassemia major with Pesaro risk score \>II
• Inherited metabolic disorders: Hurler Syndrome, Sly syndrome (MPSVIII), α-Mannosidosis, X- ALD, Osteopetrosis
• Donors who are seropositive for HIV-I/II or HTLV-I/II and female patients who are pregnant or breastfeeding will not be eligible for this study.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (1)

Memorial SloanKettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Interventions

Melphalan; Thiotepa; Clofarabine; fludarabine; Antilymphocyte Serum; thymoglobulin

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Phosphoramides; Organophosphorus Compounds; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Maria Cancio, MD
• Organization: Memorial Sloan Kettering Cancer Center

canciom@mskcc.org

212-639-7196

Study Officials

• Maria Cancio, 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: For this trial, patients will be assigned to receive one of two conditioning regimens, based on their disease, disease severity, organ status and history of red blood cell alloimmunization.

Study Record Dates

• First Submitted: July 30, 2018
• First Posted: August 3, 2018
• Study Start: July 23, 2018
• Primary Completion: November 13, 2020
• Study Completion: November 13, 2020
• Last Updated: March 24, 2021
• Results First Posted: February 24, 2021

Record last verified: 2020-11

Locations

US (1)