CLIC-1901 CAR-T Therapy for Blood Cancers

(CLIC-01 Trial)

Recruiting at 2 trial locations

Overseen By Anne Marie Clement

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Ottawa Hospital Research Institute

Disqualifiers: Genetic syndromes, Prior malignancy, Hepatitis, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

60 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, since the trial involves specific treatments like lymphodepletion, it's best to discuss your current medications with the trial team to ensure safety.

What data supports the effectiveness of the CLIC-1901 CAR-T treatment for blood cancers?

CAR-T cell therapies targeting CD19, like CLIC-1901, have shown effectiveness in treating B-cell blood cancers, as seen in the success of similar treatments like CTL019, which received 'breakthrough therapy' designation for its promising results. Additionally, CD19-CAR T cells have been effective in treating B-cell leukemia and lymphoma, indicating potential for CLIC-1901 in similar conditions. ^{1 2 3 4 5}

What safety data exists for CLIC-1901 CAR-T Therapy for Blood Cancers?

The safety data for CAR-T therapies targeting CD19, like CLIC-1901, show that common side effects include cytokine release syndrome (a condition where the immune system is overly activated) and neurotoxicity (nerve damage), with rates of 33% each. However, a specific study using a similar therapy reported no serious adverse events directly linked to the treatment, and all dose levels were well tolerated. ^{6 7 8 9 10}

What makes the CLIC-1901 CAR-T treatment unique for blood cancers?

The CLIC-1901 CAR-T treatment is unique because it uses genetically modified T cells to specifically target and attack cancer cells expressing the CD19 protein, which is common in certain blood cancers. This personalized approach harnesses the patient's own immune system to fight the cancer, offering a novel and promising option compared to traditional therapies. ^{1 3 5 11 12}

What is the purpose of this trial?

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.

Research Team

Natasha Kekre, MD

Principal Investigator

Ottawa Hospital Research Isntitute

Eligibility Criteria

This trial is for adults aged 18-75 with relapsed/refractory CD19+ blood cancers, including certain types of leukemia and lymphoma. Participants must have had a previous relapse or been unresponsive to standard treatments, and show CD19 expression in recent tests. They need good organ function but can't join if they've had gene therapy, certain other conditions or treatments, active infections like HIV/Hepatitis B/C, or are pregnant/nursing.

Inclusion Criteria

My B-cell lymphoma has relapsed twice or more, or didn’t respond to standard treatments.

My leukemia has come back or hasn't responded to treatment.

Provide written informed consent

Exclusion Criteria

I have a genetic condition like Fanconi anemia affecting my bone marrow.

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.

You have had a severe allergic reaction (anaphylaxis) to gentamicin or similar medications.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Participants undergo lymphodepletion with cyclophosphamide and fludarabine

1 week

Treatment

Single intravenous infusion of CLIC-1901 CAR-T cells

1 day

Initial Follow-up

Participants are monitored for safety and efficacy, focusing on cytokine release syndrome and other toxicities

4 weeks

Multiple visits (in-person)

Extended Follow-up

Participants are monitored for overall response rate, including complete or partial response

6 months

Treatment Details

Interventions

• CLIC-1901

Trial Overview The study is testing CLIC-1901 CAR-T cell therapy on patients with specific blood cancers who haven't responded well to other treatments. It's given as an IV infusion after pre-treatment with drugs to weaken the immune system (lymphodepletion). The first part checks safety/feasibility in 20 people; the second expands to efficacy/safety in a total of 100 participants.

Participant Groups

Group I: CLIC-1901 Experimental Treatment 1 Intervention

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

CLIC-1901 is already approved in Canada for the following indications:

Approved in Canada as CLIC-1901 for:

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

Who Is Running the Clinical Trial?

Ottawa Hospital Research Institute

Lead Sponsor

Trials

585

Recruited

3,283,000+

Findings from Research

CTL019, an anti-CD19 chimeric antigen receptor T-cell therapy, received 'breakthrough therapy' designation from the FDA, marking it as the first personalized cellular therapy for cancer, with over 100 patients treated in clinical trials.

This therapy shows promise for patients with high-risk B-cell malignancies and is part of a growing field, with nearly 30 ongoing clinical trials targeting CD19 and efforts to expand CAR T-cell therapy to other types of cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Going viral: chimeric antigen receptor T-cell therapy for hematological malignancies. Gill, S., June, CH.[2021]

Lenalidomide significantly enhances the effectiveness of CD19-targeted CAR-T cells by improving their differentiation and reducing exhaustion, which leads to better tumor control in various models of diffuse large B-cell lymphoma (DLBCL).

The combination of lenalidomide and CAR-T therapy not only reduces tumor burden but also increases the survival time of mice with DLBCL, suggesting a promising avenue for future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide overcomes the resistance to third-generation CD19-CAR-T cell therapy in preclinical models of diffuse large B-cell lymphoma. Jin, Z., Xiang, R., Qing, K., et al.[2023]

CAR T cell therapy, particularly targeting B cell maturation antigen (BCMA), has shown promising efficacy in early clinical trials for treating multiple myeloma, indicating its potential as a new treatment option.

Recent research has also demonstrated that CAR T cells targeting activated integrin β7 can effectively eliminate multiple myeloma cells, including specific B cell types, and preparations for a clinical trial are underway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cell therapy for multiple myeloma. Hasegawa, K., Hosen, N.[2020]

The study developed trispecific duoCAR-T cells that target three different B cell leukemia antigens (CD19, CD20, and CD22) to overcome the problem of antigen loss in patients with leukemia and lymphoma, showing promise in preventing relapse.

In mouse models, these duoCAR-T cells effectively rejected tumors composed of various B cell lymphoma variants, while traditional monoCAR-T cells targeting only one antigen failed to prevent tumor progression, highlighting the efficacy of multispecific targeting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trispecific CD19-CD20-CD22-targeting duoCAR-T cells eliminate antigen-heterogeneous B cell tumors in preclinical models. Schneider, D., Xiong, Y., Wu, D., et al.[2021]

In a phase 1 study involving 57 patients with relapsed/refractory multiple myeloma, LCAR-B38M CAR T cell therapy showed an impressive overall response rate of 88%, with 68% of patients achieving a complete response.

While the therapy had a manageable safety profile, with common adverse events including leukopenia and cytokine release syndrome, it demonstrated durable responses with a median progression-free survival of 15 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1, open-label study of LCAR-B38M, a chimeric antigen receptor T cell therapy directed against B cell maturation antigen, in patients with relapsed or refractory multiple myeloma. Zhao, WH., Liu, J., Wang, BY., et al.[2020]

Chimeric antigen receptor (CAR) T cell therapy targeting CD19 and CD20 has shown a promising overall response rate of 61% in treating B-cell hematologic malignancies, with a complete response rate of 42% and partial response rate of 19% across 16 studies involving 195 patients.

However, the therapy is associated with significant adverse events, including cytokine release syndrome and neurotoxicity (both at 33%), and B-cell aplasia in 54% of patients, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD 19 and anti-CD 20 CAR-modified T cells for B-cell malignancies: a systematic review and meta-analysis. Riaz, IB., Zahid, U., Kamal, MU., et al.[2023]

The FDA is currently investigating potential links between BCMA- and CD19-directed CAR T-cell therapies and the development of secondary cancers in patients, highlighting a safety concern.

Despite these concerns, both the FDA and hematologists emphasize that the life-saving benefits of these immunotherapies for treating blood cancers outweigh the risks associated with secondary malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Investigating CAR-Related T-cell Malignancies. [2023]

In a phase 1 clinical trial involving 14 patients with relapsed/refractory acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL), the novel Sleeping Beauty (SB) CD19-specific CAR T-cell therapy demonstrated a strong safety profile, with no serious adverse events directly linked to the treatment and only mild cytokine release syndrome observed.

Efficacy results showed that 38% of patients with ALL achieved complete remission or incomplete count recovery, and 50% of patients with diffuse large B-cell lymphoma (DLBCL) also achieved complete remission, indicating promising antitumor activity of the SB-based CAR constructs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleeping beauty generated CD19 CAR T-Cell therapy for advanced B-Cell hematological malignancies. Singh, H., Srour, SA., Milton, DR., et al.[2023]

Anti-CD19 CAR-modified T cells have demonstrated a 48% overall response rate in treating B-cell malignancies, with complete responses observed in 24% of patients across six phase I clinical trials involving 50 patients.

The study found that conditioning chemotherapy significantly improves progression-free survival (PFS), making it a crucial factor for enhancing the efficacy of CAR T-cell therapy, while the treatment was generally well tolerated with temporary adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD19 chimeric antigen receptor-modified T cells for B-cell malignancies: a systematic review of efficacy and safety in clinical trials. Zhu, Y., Tan, Y., Ou, R., et al.[2022]

CD19-directed CAR T cell therapy has been successfully approved by the FDA and European Medicines Agency for treating specific B cell malignancies, demonstrating significant efficacy across multiple clinical trials.

Despite similar overall effectiveness, there are important differences in manufacturing, availability, and toxicity profiles among various CAR T cell products, highlighting the need for careful consideration of these factors in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

State of the art in CAR T cell therapy for CD19+ B cell malignancies. Frigault, MJ., Maus, MV.[2021]

CAR T-cells are engineered T-cells that target the CD19 antigen, showing promising initial results in treating various B-cell malignancies, including acute lymphocytic leukaemia and chronic lymphocytic leukaemia.

While the treatment shows potential, there are significant differences in patient responses and notable side effects that require careful management, highlighting the need for personalized approaches in therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-cells fighting B-cell lymphoproliferative malignancies: the emerging field of CD19 CAR T-cell therapy. Heijink, DM., Kater, AP., Hazenberg, MD., et al.[2017]

Chimeric antigen receptor (CAR) therapy, particularly targeting CD19, has shown significant efficacy in treating patients with chemorefractory B cell malignancies, leading to its potential regulatory approval as a cell-based immunotherapy.

While CAR therapy is effective, it is associated with toxicities such as cytokine release syndrome, neurotoxicity, and B cell aplasia, which require careful management in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biology and clinical application of CAR T cells for B cell malignancies. Davila, ML., Sadelain, M.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Going viral: chimeric antigen receptor T-cell therapy for hematological malignancies. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Lenalidomide overcomes the resistance to third-generation CD19-CAR-T cell therapy in preclinical models of diffuse large B-cell lymphoma. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cell therapy for multiple myeloma. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Trispecific CD19-CD20-CD22-targeting duoCAR-T cells eliminate antigen-heterogeneous B cell tumors in preclinical models. [2021]

5. England pubmed.ncbi.nlm.nih.gov

A phase 1, open-label study of LCAR-B38M, a chimeric antigen receptor T cell therapy directed against B cell maturation antigen, in patients with relapsed or refractory multiple myeloma. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Anti-CD 19 and anti-CD 20 CAR-modified T cells for B-cell malignancies: a systematic review and meta-analysis. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

FDA Investigating CAR-Related T-cell Malignancies. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Sleeping beauty generated CD19 CAR T-Cell therapy for advanced B-Cell hematological malignancies. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Anti-CD19 chimeric antigen receptor-modified T cells for B-cell malignancies: a systematic review of efficacy and safety in clinical trials. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

State of the art in CAR T cell therapy for CD19+ B cell malignancies. [2021]

11. Netherlands pubmed.ncbi.nlm.nih.gov

T-cells fighting B-cell lymphoproliferative malignancies: the emerging field of CD19 CAR T-cell therapy. [2017]

12. Japan pubmed.ncbi.nlm.nih.gov

Biology and clinical application of CAR T cells for B cell malignancies. [2023]