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

NCT ID: NCT03765177

Last Updated: 2025-08-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-16
• Study Completion Date: 2042-06-30

Brief Summary

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

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.

Conditions

Acute Lymphoblastic Leukemia; Non-Hodgkin's Lymphoma; Chronic Lymphocytic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CLIC-1901

A single Intravenous infusion of CLIC-1901 will be given.

Group Type: EXPERIMENTAL

CLIC-1901

Intervention Type: BIOLOGICAL

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.

Interventions

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.

Intervention Type: BIOLOGICAL

Other Intervention Names

autologous anti-CD19 CAR-T cells

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ottawa Hospital Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Natasha Kekre, MD

Role: PRINCIPAL_INVESTIGATOR

Ottawa Hospital Research Isntitute

Locations

Vancouver General Hospital

Vancouver, British Columbia, Canada

Site Status: RECRUITING

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Site Status: NOT_YET_RECRUITING

The Ottawa Hospital - General Campus

Ottawa, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Natasha Kekre, MD

Role: CONTACT

nkekre@toh.on.ca

613-737-8899 ext. 71064

Anne Marie Clement

Role: CONTACT

amclement@ohri.ca

6137378899 ext. 73389

Facility Contacts

Kevin Song, MD

Role: primary

KSong@bccancer.bc.ca

604-875-4863

Claudia Piechnik, BSc

Role: backup

claudia.piechnik@bccancer.bc.ca

604-875-4111 ext. 22958

Chantalle Menard, MD

Role: primary

cmenard@cancercare.mb.ca

2047878687

Natasha Kekre, MD, MPH, FRCP

Role: primary

nkekre@toh.on.ca

613-737-8899 ext. 71064

Vanessa Lopez-Ozuna, MD, PhD

Role: backup

vlopez@ohri.ca

613-737-8899 ext. 71264

References

Kekre N, Hay KA, Webb JR, Mallick R, Balasundaram M, Sigrist MK, Clement AM, Nielsen JS, Quizi J, Yung E, Brown SD, Dreolini L, Waller DD, Smazynski J, Gierc NS, Loveless BC, Clark K, Dyer T, Hogg R, McCormick L, Gignac M, Bell S, Chapman DM, Bond D, Yong S, Fung R, Lockyer HM, Hodgson V, Murphy C, Subramanian A, Wiebe E, Yoganathan P, Medynski L, Vaillan DC, Black A, McDiarmid S, Kennah M, Hamelin L, Song K, Narayanan S, Rodrigo JA, Dupont S, Hawrysh T, Presseau J, Thavorn K, Lalu MM, Fergusson DA, Bell JC, Atkins H, Nelson BH, Holt RA. CLIC-01: Manufacture and distribution of non-cryopreserved CAR-T cells for patients with CD19 positive hematologic malignancies. Front Immunol. 2022 Dec 19;13:1074740. doi: 10.3389/fimmu.2022.1074740. eCollection 2022.

Reference Type: DERIVED

PMID: 36601119 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33766105 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33741670 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33072399 (View on PubMed)

Other Identifiers

CLIC-01 Study

Identifier Type: -

Identifier Source: org_study_id