CAR-T Cell Therapy for Acute Myeloid Leukemia

(AMpLify Trial)

Recruiting at 9 trial locations

Overseen By Caribou Biosciences

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Caribou Biosciences, Inc.

Must not be taking: CAR-T therapy

Disqualifiers: Acute promyelocytic leukemia, HIV, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

12 Participants Needed

Trial Summary

What is the purpose of this trial?

CB-012 is an allogeneic chimeric antigen receptor (CAR-T) cell therapy that targets C-type lectin-like molecule-1 (CLL-1). This is a Phase 1 study to evaluate the safety, preliminary efficacy, and pharmacokinetics, of CB-012 (the study treatment) in adults with acute myeloid leukemia (AML) that has come back after prior treatment (relapsed) or did not respond or is no longer responding to other treatment (refractory). Participants must have received at least 1 but not more than 3 prior lines of treatment for AML .

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment CB-012 for acute myeloid leukemia?

CAR T-cell therapy, which is similar to CB-012, has shown success in treating other blood cancers like B-cell malignancies and acute lymphoblastic leukemia (ALL), leading to complete remission in many patients. This suggests potential for effectiveness in acute myeloid leukemia (AML) as well, although AML presents unique challenges. ^{1 2 3 4 5}

Is CAR-T cell therapy safe for humans?

CAR-T cell therapies have been approved for some blood cancers, but they can have complex side effects like cytokine release syndrome (a severe immune reaction) and neurotoxicity (nerve damage). Research shows that some CAR-T cells, like those targeting LILRB4 in AML, can be effective without harming normal cells, suggesting potential safety improvements. ^{6 7 8 9 10}

How is the treatment CB-012 different from other treatments for acute myeloid leukemia?

CB-012 is a CAR-T cell therapy, which is a unique treatment that uses genetically engineered T cells to specifically target and destroy leukemia cells. This approach is different from traditional treatments because it aims to improve outcomes by directly targeting cancer cells, although finding specific targets for AML remains challenging. ^{1 2 3 5 11}

Eligibility Criteria

This trial is for adults with acute myeloid leukemia (AML) that's returned after treatment or isn't responding to current treatments. They should be fit for a stem cell transplant, have an ECOG score of 0-1, and can't have had more than three prior AML treatments. Participants need good kidney, liver, lung, and heart function and must use effective birth control if they can have children.

Inclusion Criteria

There are no treatments left that doctors think could significantly extend my life.

My AML cancer has come back or is not responding to treatment.

I have had 3 or fewer previous cancer treatments.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Part A: Participants receive increasing doses of CB-012 using a 3+3 design to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE)

4 weeks

Multiple visits (in-person)

Dose Expansion

Part B: Participants receive CB-012 at the RDE and/or MTD determined in Part A to determine the recommended phase 2 dose (RP2D)

12 months

Regular visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• CB-012

Trial Overview The study tests CB-012, a CRISPR-edited CAR-T therapy targeting CLL-1 in AML patients. It's a Phase 1 trial focusing on safety, how well it works (efficacy), and how the body processes the drug (pharmacokinetics).

Participant Groups

Group I: Dose Expansion of CB-012 Experimental Treatment 1 Intervention

Part B (Dose Expansion) - participants will be enrolled to receive CB-012 at the RDE and/or MTD determined in Part A in order to the determine the RP2D.

Group II: Dose Escalation of CB-012 Experimental Treatment 1 Intervention

Part A (Dose Escalation) of CB-012 with increasing doses using a 3+3 design, during which the MTD and/or RDE will be identified.

CB-012 is already approved in United States for the following indications:

Approved in United States as CB-012 for:

Who Is Running the Clinical Trial?

Caribou Biosciences, Inc.

Lead Sponsor

Trials

5

Recruited

360+

Findings from Research

CAR T-cell therapy shows promise in improving outcomes for patients with acute myeloid leukemia (AML), a condition with historically poor prognosis.

A significant challenge for the effectiveness of CAR T-cell therapy in AML is the identification of specific target antigens on leukemia cells, as well as the risk of immune escape due to changes in these antigens and a suppressive tumor environment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current challenges for CAR T-cell therapy of acute myeloid leukemia. Sauer, T., Rooney, CM.[2020]

CAR T-cell therapy has the potential to improve outcomes for patients with acute myeloid leukemia (AML) by specifically targeting leukemia cells, but there are significant challenges to its effectiveness and safety.

Strategies being explored to enhance CAR T-cell therapy in AML include targeting specific leukemia antigens to reduce side effects, using checkpoint inhibitors to counteract immune suppression caused by leukemia, and developing allogenic CAR T cells to make the treatment more accessible to patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospect of CAR T-cell therapy in acute myeloid leukemia. Badar, T., Manna, A., Gadd, ME., et al.[2022]

Immunotherapy, particularly chimeric antigen receptor (CAR) T cell therapy, is being explored as a promising approach to treat acute myeloid leukemia (AML), building on the understanding of how leukemic cells interact with their bone marrow environment.

While CAR T cell therapy has shown success in treating B-cell malignancies, there are significant challenges in adapting this treatment for AML, and ongoing preclinical and clinical studies are working to address these issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CARving the Path to Allogeneic CAR T Cell Therapy in Acute Myeloid Leukemia. Pasvolsky, O., Daher, M., Alatrash, G., et al.[2022]

CD123 chimeric antigen receptor (CAR) redirected T cells have shown strong antileukemic activity, indicating a promising new approach for treating acute myeloid leukemia.

The development of CD123 CARs provides insights into enhancing immunotherapy strategies, highlighting the need for novel treatments in this challenging disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myeloid leukemia therapeutics: CARs in the driver's seat. Mardiros, A., Brown, CE., Budde, LE., et al.[2021]

CAR-T cell therapy, which targets specific antigens on tumor cells, has shown promising results in achieving complete remission in patients with relapsed and refractory B-type acute lymphoblastic leukemia (ALL), leading researchers to explore its application in other blood cancers like acute myeloid leukemia (AML).

Despite the challenges posed by AML, which has a lower 5-year survival rate of 31.7% due to treatment resistance, CAR-T therapies targeting antigens such as CD33, CD123, FLT3, and CLL-1 are being investigated, highlighting the potential for improved outcomes in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cells Immunotherapies for the Treatment of Acute Myeloid Leukemia-Recent Advances. Zarychta, J., Kowalczyk, A., Krawczyk, M., et al.[2023]

In a phase I trial involving 12 younger patients with relapsed or refractory B-cell acute lymphoblastic leukemia, the use of chimeric antigen receptor T cells targeting CD19 and CD22 showed manageable toxicity levels.

Out of the 12 patients, 5 achieved complete responses, indicating promising efficacy of this treatment approach in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting CD19-CD22 Aids Younger Patients with ALL. [2021]

Chimeric antigen receptor (CAR) T-cell therapies targeting myeloid antigens have been under research for over a decade for treating relapsed/refractory acute myeloid leukemia (AML), but none have reached approval yet due to limited clinical benefits.

A first-in-human clinical trial of GMR CAR T-cells targeting CD116-positive myeloid neoplasms, including AML, began in 2021, indicating a potential new treatment avenue for patients with these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current status and future perspective of CAR T-cell therapy for acute myeloid leukemia]. Nakazawa, Y.[2022]

The study identifies LILRB4 as a promising tumor-associated antigen specifically expressed on monocytic acute myeloid leukemia (AML) cells, allowing for targeted therapy without affecting normal blood stem cells.

The novel anti-LILRB4 CAR-T cells demonstrated effective targeting and destruction of LILRB4+ AML cells in laboratory tests, while showing no toxicity to normal hematopoietic progenitors, suggesting a safer treatment option for patients with monocytic AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel Anti-LILRB4 CAR-T Cell for the Treatment of Monocytic AML. John, S., Chen, H., Deng, M., et al.[2020]

CAR-T cell therapies, while effective for treating relapsed or refractory blood cancers, can lead to serious adverse effects such as cytokine release syndrome (CRS) and neurotoxicity, which complicate patient management.

The review discusses the pathophysiology and management strategies for these adverse events, and highlights ongoing research aimed at modifying CAR-T cells to reduce toxicity and improve patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complete spectrum of adverse events associated with chimeric antigen receptor (CAR)-T cell therapies. Yang, C., Nguyen, J., Yen, Y.[2023]

A novel second-generation chimeric antigen receptor (CAR) targeting CD33 has been developed, showing effectiveness in redirecting T cells to kill acute myeloid leukemia (AML) cells, which express CD33 in about 90% of cases.

In pre-clinical studies, this CAR therapy demonstrated significant anti-leukemia effects both in vitro and in vivo, effectively preventing leukemia development and delaying disease progression in mice, supporting its potential as a clinical treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD33 chimeric antigen receptor targeting of acute myeloid leukemia. O'Hear, C., Heiber, JF., Schubert, I., et al.[2021]

CAR T-cell therapy for acute myeloid leukemia (AML) faces challenges due to the lack of specific surface antigens, but advancements are being made to improve its effectiveness.

Potential strategies to enhance the safety and efficacy of CAR T-cell therapy for AML include reducing the potency of CAR T cells, using transient CAR T cells during pre-transplant conditioning, and employing gene-edited allogeneic stem cell transplants to support sustained anti-AML activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How close are we to CAR T-cell therapy for AML? Gill, SI.[2021]

References

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

Current challenges for CAR T-cell therapy of acute myeloid leukemia. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Prospect of CAR T-cell therapy in acute myeloid leukemia. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

CARving the Path to Allogeneic CAR T Cell Therapy in Acute Myeloid Leukemia. [2022]

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

Acute myeloid leukemia therapeutics: CARs in the driver's seat. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

CAR-T Cells Immunotherapies for the Treatment of Acute Myeloid Leukemia-Recent Advances. [2023]

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

Targeting CD19-CD22 Aids Younger Patients with ALL. [2021]

7. Japan pubmed.ncbi.nlm.nih.gov

[Current status and future perspective of CAR T-cell therapy for acute myeloid leukemia]. [2022]

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

A Novel Anti-LILRB4 CAR-T Cell for the Treatment of Monocytic AML. [2020]

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

Complete spectrum of adverse events associated with chimeric antigen receptor (CAR)-T cell therapies. [2023]

10. Italy pubmed.ncbi.nlm.nih.gov

Anti-CD33 chimeric antigen receptor targeting of acute myeloid leukemia. [2021]

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

How close are we to CAR T-cell therapy for AML? [2021]