CLIC-1901 for the Treatment of Patients With Relapsed/Refractory CD19 Positive Hematologic Malignancies (CLIC-01)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Non-Hodgkin's Lymphoma; Acute Lymphoblastic Leukemia; Chronic Lymphocytic Leukemia
• Intervention / Treatment: Biological: CLIC-1901

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Natasha Kekre, MD; Phone Number: 71064 613-737-8899; Email: nkekre@toh.on.ca
• Study Contact Backup: Name: Anne Marie Clement; Phone Number: 73389 6137378899; Email: amclement@ohri.ca

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z1M9
      • Recruiting
      • Vancouver General Hospital
      • Contact: Kevin Song, MD; Phone Number: 604-875-4863; Email: KSong@bccancer.bc.ca
      • Contact: Claudia Piechnik, BSc; Phone Number: 22958 604-875-4111; Email: claudia.piechnik@bccancer.bc.ca
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • Not yet recruiting
      • CancerCare Manitoba
      • Contact: Chantalle Menard, MD; Phone Number: 2047878687; Email: cmenard@cancercare.mb.ca
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Recruiting
      • The Ottawa Hospital - General Campus
      • Contact: Natasha Kekre, MD, MPH, FRCP; Phone Number: 71064 613-737-8899; Email: nkekre@toh.on.ca
      • Contact: Vanessa Lopez-Ozuna, MD, PhD; Phone Number: 71264 613-737-8899; Email: vlopez@ohri.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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

2. 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.
3. Adequate organ function
4. Participant age: 18 to 75 years.
5. Provide written informed consent

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Isolated extra-medullary disease.
2. Participants with concomitant genetic syndrome, such as Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known familial bone marrow failure syndrome.
3. Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease.
4. Prior treatment with any gene therapy product.
5. 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.
6. Presence of active Graft Versus Host Disease requiring systemic therapy.
7. 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.
8. Active Central Nervous System (CNS) involvement by malignancy, defined by CNS-3 per National Comprehensive Cancer Network guidelines.
9. History of anaphylaxis to gentamicin or its derivatives.
10. Participant has received an investigational agent within the 30 days prior to enrolment visit.
11. Pregnant or nursing women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CLIC-1901; A single Intravenous infusion of CLIC-1901 will be given.	Biological: CLIC-1901; 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.; Other Names: autologous anti-CD19 CAR-T cells

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Ottawa Hospital Research Institute
• Investigators: Principal Investigator: Natasha Kekre, MD, Ottawa Hospital Research Isntitute

Publications and helpful links

General Publications

• Castillo G, Lalu M, Asad S, Foster M, Kekre N, Fergusson D, Hawrysh T, Atkins H, Thavorn K, Montroy J, Schwartz S, Holt R, Broady R, Presseau J; GO CART team. Hematologists' barriers and enablers to screening and recruiting patients to a chimeric antigen receptor (CAR) T cell therapy trial: a theory-informed interview study. Trials. 2021 Mar 25;22(1):230. doi: 10.1186/s13063-021-05121-y.
• Castillo G, Lalu MM, Asad S, Foster M, Kekre N, Fergusson DA, Hawrysh T, Atkins H, Thavorn K, Montroy J, Schwartz S, Holt RA, Broady R, Presseau J. Navigating choice in the face of uncertainty: using a theory informed qualitative approach to identifying potential patient barriers and enablers to participating in an early phase chimeric antigen receptor T (CAR-T) cell therapy trial. BMJ Open. 2021 Mar 19;11(3):e043929. doi: 10.1136/bmjopen-2020-043929.
• Foster M, Fergusson DA, Hawrysh T, Presseau J, Kekre N, Schwartz S, Castillo G, Asad S, Fox G, Atkins H, Thavorn K, Montroy J, Holt RA, Monfaredi Z, Lalu MM. Partnering with patients to get better outcomes with chimeric antigen receptor T-cell therapy: towards engagement of patients in early phase trials. Res Involv Engagem. 2020 Oct 14;6:61. doi: 10.1186/s40900-020-00230-5. eCollection 2020.

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2019
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 31, 2037

Study Registration Dates

• First Submitted: December 4, 2018
• First Submitted That Met QC Criteria: December 4, 2018
• First Posted (Actual): December 5, 2018

Study Record Updates

• Last Update Posted (Estimated): November 3, 2023
• Last Update Submitted That Met QC Criteria: November 1, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Chimeric Antigen Receptor T cells; CLIC-1901; anti-CD19 CAR-T cells
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Neoplasms by Site; Disease Attributes; Hematologic Diseases; Leukemia, Lymphoid; Leukemia, B-Cell; Chronic Disease; Hematologic Neoplasms; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell
• Other Study ID Numbers: CLIC-01 Study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No