CAR-T Cell Therapy for Acute Myeloid Leukemia

(AMpLify Trial)

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CB-012, a type of cell therapy designed to target and attack specific cancer cells in people with acute myeloid leukemia (AML). The goal is to determine if CB-012 is safe and effective for those whose leukemia has returned or hasn't responded to other treatments. Participants should have AML that has either returned or not responded to treatment and must have tried at least one but no more than three different treatment plans. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

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.

Is there any evidence suggesting that CB-012 is likely to be safe for humans?

Research has shown that CAR-T cell therapies, such as CB-012, are under investigation for treating acute myeloid leukemia (AML). These therapies use specially altered immune cells to target cancer cells. Safety remains a major concern when testing new treatments like CB-012.

In past studies with CAR-T therapies, some patients experienced side effects such as fever, low blood pressure, or difficulty breathing. However, medical care can manage many of these side effects. For CB-012, researchers aim to find a dose that is both safe and effective.

Since this trial is in an early phase, the main focus is on safety. The treatment has not been tested in many people yet. This trial will help researchers understand how well patients tolerate CB-012 and what side effects might occur. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for acute myeloid leukemia, which typically involve chemotherapy and stem cell transplants, CB-012 is a CAR-T cell therapy that uses genetically engineered T cells to specifically target and destroy cancer cells. This approach is exciting because it harnesses the body's own immune system, offering a more precise attack on leukemia with potentially fewer side effects. Additionally, CAR-T cell therapy has shown promise in other blood cancers, suggesting that it might provide a more effective and long-lasting response for patients with acute myeloid leukemia. Researchers are particularly interested in CB-012's ability to deliver targeted treatment while minimizing damage to healthy cells, potentially leading to improved outcomes for patients.

What evidence suggests that CB-012 might be an effective treatment for acute myeloid leukemia?

Research has shown that CAR-T cell therapies hold promise for treating acute myeloid leukemia (AML). One study found that similar treatments helped some patients remain disease-free for over a year. Another study demonstrated that CAR-T cells targeting a different marker were safe and effective against leukemia in children with AML. In this trial, participants will receive the specific therapy CB-012, which targets a molecule called CLL-1 found on AML cells. By focusing on CLL-1, CB-012 aims to attack and destroy leukemia cells. Early results suggest that CAR-T therapies can be safe and might work well for AML, but more research is needed to confirm these findings. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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).

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11938459/

Recent advances of CAR-T cells in acute myeloid leukemia The overall and disease-free survival rates at 1 year were 4/7 and 3/7, respectively. This approach directly realizes the “seamless interface” ...

2. cell.com cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(25)00261-8

CAR-T cell therapy for treatment of acute myeloid leukemia ... Safety and anti-leukemic activity of CD123-CAR T cells in pediatric patients with AML: preliminary results from a phase 1 trial. Blood. 2022 ...

3. nature.com nature.com/articles/s41392-025-02269-w

CAR-T cell therapy for cancer: current challenges and ... 2-targeted CAR has proven effective in treating gastrointestinal tumors in a study including 37 patients (NCT04196413), with an overall response ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06128044

CRISPR-Edited Allogeneic Anti-CLL-1 CAR-T Cell Therapy ... 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 ...

5. ehoonline.biomedcentral.com ehoonline.biomedcentral.com/articles/10.1186/s40164-025-00651-6

Breakthroughs of CAR T-cell therapy in acute myeloid ... A trial of CD19 CAR T-cell in ten t(8;21) AML patients showed a high safety profile, without severe non-hematological toxicities, and remarkable ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11987445/

Breakthroughs of CAR T-cell therapy in acute myeloid ... The 2024 ASH Meeting highlighted several cutting-edge advancements in AML-directed CAR T therapies, including clinical trials targeting CD33, CD123, CLL1, CD19 ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S014521262400064X

Safety and efficacy of chimeric antigen receptor T-cell ... This meta-analysis highlights the potential of CAR T-cell therapy in AML treatment, especially when integrated with certain prior treatments and conditioning ...