A Study of MT-101 in Subjects With CD5+ Relapsed/Refractory TCL

Study Overview
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Brief Summary
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This is a Phase 1/2 study to test the safety, tolerability, and efficacy of the investigational agent MT-101 in patients with T cell Lymphoma. MT-101 is made with myeloid cells collected from the patient's blood. The myeloid cells are modified and later infused back into their veins. The modified myeloid cells recognize the tumor cells and are designed to target and kill them.

Detailed Description
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The research study is divided into two parts. The first part will be to determine the safety and tolerability of the study drug product. During this part of the study, there will be 4 groups of study patients. The first group of patients will receive a low dose of cells, the second group will receive the low dose of cells and lymphodepleting chemotherapy to reduce the number of T cells in the blood, the third group will receive a higher dose of cells, and the fourth group will receive the higher dose of cells and lymphodepleting chemotherapy to reduce the number of T cells in the blood. In the second part of the study, cells with or without chemotherapy will be administered based on results of Part 1 and the safety, tolerability, and efficacy of MT-101 will be assessed. All patient groups will receive 6 doses of drug product over 3 weeks.

Official Title
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A Phase 1/2, Open-Label, First-in-human, Multiple Ascending Dose Multicenter Study of MT-101 in Subjects With CD5+ Relapsed/Refractory T Cell Lymphoma

Conditions
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Lymphoma, T-Cell, Peripheral, Lymphoma, T-Cell, Cutaneous, Mycosis Fungoides, Adoptive Cellular Immunotherapy, Cell Therapy

Intervention / Treatment
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* Biological: MT-101
* Other: MT-101 + Conditioning (Lymphodepleting) Chemotherapy


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Adults age > or equal to18 at the time the Informed Consent is signed Refractory or relapsed pathologically confirmed T Cell Lymphoma (TCL): Peripheral T cell Lymphoma not otherwise specified (PTCL-NOS) , Angioimmunoblastic T cell Lymphoma (AITL), ALK-negative anaplastic large cell lymphoma (ALCL), ALK-positive ALCL, or Mycosis Fungoides (MF) stage IIB-IV including large cell transformation CD5-expressing tumor by IHC or flow cytometry of tumor biopsy within 3 months of Screening or at Screening Eastern Cooperative Oncology Group performance status < 2 Adequate organ function as defined in the protocol. Key Exclusion Criteria: B1 and B2 disease (as defined in protocol for subjects with MF) Known central nervous system involvement by PTCL History of allogeneic transplant History of intolerance to leukapheresis, plasmapheresis, or blood donation Pregnant or nursing women Any acute illness including fever (> 100.4°F or > 38°C), except fever related to tumor Active systemic bacterial, fungal, or viral infection Active chronic infection Other primary malignancies, except adequately treated malignancies or complete remission Active autoimmune disease that has required systemic therapy in the last 2 years History of hemophagocytic lymphohistiocytosis History of severe, immediate hypersensitivity reaction attributed to penicillin Any other condition that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with the study requirements.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Multi-ascending dose escalation
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 and Cohort 3<br>MT-101 | Biological: MT-101<br>* CD5 ATAK cells<br>|
| Experimental: Cohort 2 and Cohort 4<br>MT-101 preceded by conditioning (lymphodepleting) chemotherapy | Other: MT-101 + Conditioning (Lymphodepleting) Chemotherapy<br>* IV administration of fludarabine and cyclophosphamide<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability of MT-101 | Safety and tolerability of the drug will be determined based on observed adverse events (AEs), including all potential dose limiting toxicities. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MT-101 cell kinetics in blood | The quantity of MT-101 RNA in the blood. | 4 weeks | 
| The objective response rate | The ORR is defined as the number (%) of subjects achieving a best overall response of complete response (CR) or partial response (PR) | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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T Cell Lymphoma, PTCL, CTCL, MF, MT-101, CD5 chimeric antigen receptor, Myeloid cells, Monocytes, Chimeric Antigen Receptor, CAR Monocyte Therapy