Study Evaluating Safety and Efficacy of UCART Targeting CS1 in Patients With Relapsed/Refractory Multiple Myeloma (MELANI-01)

Study Overview
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Brief Summary
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This is a Phase I, FIH, open-label, dose escalation study evaluating Safety and Efficacy of UCART targeting CS1 in patients with Relapsed or Refractory Multiple Myeloma (MM). The purpose of this study is to evaluate the safety and clinical activity of UCARTCS1A and to determine the Maximum Tolerated Dose (MTD).

Official Title
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Phase I, Open-label Dose-escalation Study to Evaluate the Safety, Expansion, Persistence and Clinical Activity of UCARTCS1A (Allogenic Engineered T-cells Expressing Anti-CS1 Chimeric Antigen Receptor) Administered in Patients With Relapsed/Refractory Multiple Myeloma

Conditions
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Relapsed/Refractory Multiple Myeloma

Intervention / Treatment
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* Biological: UCARTCS1A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with confirmed diagnosis of active multiple myeloma (as defined by International Myeloma Working Group [IMWG] criteria) who have relapsed/refractory disease after and have received at least 3 prior lines of prior therapy. Eastern Cooperative Oncology Group Performance Status of 0 or 1; No previous treatment with investigational gene targeting CS1 or chimeric antigen receptor therapy targeting CS1 Adequate organ function, including bone marrow, renal, hepatic, pulmonary, and cardiac function based on the last assessment performed within the screening period. Other criteria may apply. Exclusion Criteria: Previous treatment with investigational gene therapy targeting CS1 or chimeric antigen receptor therapy targeting CS1; Any cellular therapy (other than autologous or allogenic HSCT) within 60 days prior to enrollment; Prior treatment with rituximab or other anti-CD20 therapy within 3 months Any known active or uncontrolled infection Autologous hematopoietic stem cell transplantation (HSCT) within 12 weeks prior to enrollment; any cellular therapy (other than autologous) within 60 days prior to enrollment; prior allogeneic HSCT. Seropositive for Hepatitis C virus or positive for Hepatitis B surface antigen or core antibody. Presence of active and clinically relevant central nervous system disorder, such as epilepsy, generalized seizure disorder, paresis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, or organic brain syndrome.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation<br>Several tested doses of UCARTCS1A until the Maximum Tolerated Dose (MTD) is identified. | Biological: UCARTCS1A<br>* Allogenic engineered T-cells expressing anti- CS1 Chimeric Antigen Receptor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of UCARTCS1A | Incidence, nature and severity of adverse events and serious adverse events (SAEs) throughout the study. | 24 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Assessment | At Day 35, Day 56 (M2), Day 84 (M3), Follow-up [Q3M up to Month 24; i.e., Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 21 and Month 24 | 24 months | 
| Duration of Response | Time Frame: From the date of the initial response to the date of disease progression or death from any cause, whichever occurs first, assessed up to Month 24] | 24 months | 
| Progression Free Survival | From the first day of study treatment to the date of disease progression or death from any cause, whichever occurs first, assessed up to Month 24 | 24 months | 
| Overall Survival | From the first day of study treatment to the date of death from any cause, assessed up to Month 24 | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Myeloma, Chimeric Antigen Receptor T-Cell (CART-T) therapy, Transcription Activator-Like Effector Nuclease (TALEN), Allogeneic