CLIC-1901 for the Treatment of Patients With Relapsed/Refractory CD19 Positive Hematologic Malignancies

Study Overview
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Brief Summary
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The investigators propose an early phase study defined as a phase I/II trial assessing safety, feasibility and efficacy of CLIC-1901 autologous anti-CD19 Chimeric Antigen Receptor T cells (CAR-T) cells for participants with relapsed/refractory CD19 positive (CD19+) Acute Lymphoblastic Leukemia (ALL) and non-Hodgkin's Lymphoma (NHL). The Initial Stage of the study (n=20 participants) will focus on feasibility and safety while the Extended Stage will include all participants enrolled in the study (n=additional 80 participants for a total of 100) and will focus on efficacy and safety outcomes. In the proposed trial, we will administer our CAR-T cell product to these participants as a single infusion. Participants will undergo (a) lymphodepletion with cyclophosphamide and fludarabine, followed by (b) infusion of autologous CLIC-1901 CAR-T cells. All treatments will be delivered intravenously.

Detailed Description
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The investigators have designed a two-stage, single-arm, open-label early phase study to determine the safety and efficacy of CLIC-1901 cell therapy in patients with CD19+ ALL and NHL. The primary objective in the initial stage of 20 participants will be to evaluate the feasibility of our protocol and the safety and tolerability of infusing autologous CLIC-1901 cells into patients with relapsed/refractory CD19+ ALL or NHL. Once 20 participants have been treated and the treatment is deemed safe, up to 80 more participants will be enrolled in an extension stage where the primary objective will be overall response rate (defined as complete or partial response) at 6 months after CLIC-1901 infusion.

Official Title
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Canadian-Led Immunotherapies in Cancer: CLIC-1901 for the Treatment of Patients With Relapsed/Refractory CD19 Positive Hematologic Malignancies

Conditions
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Acute Lymphoblastic Leukemia, Non-Hodgkin's Lymphoma, Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Biological: CLIC-1901


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must have relapsed or refractory CD19+ disease as defined by one of the following: a. Relapsed or refractory acute lymphoblastic leukemia or chronic lymphocytic leukemia as defined by one of the following: i. Second or greater relapse ii. Any relapse after allogeneic stem cell transplantation (SCT) iii. Chemorefractory as defined by not achieving CR after 2 cycles of a standard induction chemotherapy or one cycle of salvage therapy b. Histologically confirmed B-cell non-Hodgkin's lymphoma including but not limited to diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, or transformed follicular lymphoma, Richter's, Burkitt's or Mantle Cell lymphoma with one of the following: i. Second or greater relapse ii. Any relapse after autologous or allogeneic SCT iii. Chemorefractory as defined by not achieving CR after 2 cycles of a standard chemotherapy or one cycle of salvage therapy All eligible participants must have documentation of CD19 tumour expression demonstrated in tissue biopsy, bone marrow or peripheral blood within the 3 months prior to study screening. Adequate organ function Participant age: 18 to 75 years. Provide written informed consent Exclusion Criteria: An individual who meets any of the following criteria will be excluded from participation in this study: Isolated extra-medullary disease. Participants with concomitant genetic syndrome, such as Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known familial bone marrow failure syndrome. Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease. Prior treatment with any gene therapy product. Participants with polymerase chain reaction (PCR) positive hepatitis B, hepatitis C, or Human Immunodeficiency Virus (tested within 8 weeks of screening), or any uncontrolled infection at screening. Presence of active Graft Versus Host Disease requiring systemic therapy. Participants who have undergone allogeneic SCT less than 6 months prior to CLIC-1901 cell infusion or who have undergone donor lymphocyte infusion less than 6 weeks prior to CLIC-1901 cell infusion. Active Central Nervous System (CNS) involvement by malignancy, defined by CNS-3 per National Comprehensive Cancer Network guidelines. History of anaphylaxis to gentamicin or its derivatives. Participant has received an investigational agent within the 30 days prior to enrolment visit. Pregnant or nursing women.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: CLIC-1901<br>A single Intravenous infusion of CLIC-1901 will be given. | Biological: CLIC-1901<br>* Participants will undergo (a) lymphodepletion with cyclophosphamide and fludarabine, followed by (b) infusion of autologous CLIC-1901 CAR-T cells. All treatments will be delivered intravenously.<br>* Other names: autologous anti-CD19 CAR-T cells;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants experiencing either Grade 3 or 4 cytokine release syndrome. | Grade 3 or 4 neurological toxicity, other Grade 3 or 4 toxicity (by CTCAE 4.03) or non-relapse related death. | Within the first 28 days of CAR-T infusion | 
| Proportion of participants with complete (CR) or partial response (PR) to CLIC-1901 | Complete response, partial response and disease progression reviewed 6 months after CAR-T cell infusion | 6 months after CAR-T cell infusion | 
| Meeting enrollment targets | The feasibility outcome has been met 20 participant in 12 months - currently in next phase and on track to finish on or before October 2024 | First 20 participants within 12 months and next 80 participants within 4 years of opening the second stage. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chimeric Antigen Receptor T cells, CLIC-1901, anti-CD19 CAR-T cells