CAR T Therapy for Multiple Myeloma

Recruiting at 39 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: AstraZeneca

Must be taking: PI, IMiD, antiCD38

Disqualifiers: Invasive malignancy, Cardiac conditions, CNS involvement, others

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

Compensation: Varies

Number of Visits: 2

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called GC012F, a therapy using modified immune cells to target and fight multiple myeloma, a type of blood cancer. The goal is to determine if this treatment can help individuals whose cancer has returned or isn't responding to other treatments. The trial seeks participants who have undergone at least three different treatments for multiple myeloma and still show signs of the disease. Participants will receive the treatment through a single infusion. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether 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 this treatment is likely to be safe for humans?

In previous studies, GC012F has shown promise in treating multiple myeloma. Research indicates that this treatment was generally safe for patients, with many experiencing lasting improvements. One study found that 89.3% of participants responded well to the treatment, indicating effectiveness for most people.

Regarding safety, GC012F was well-tolerated, meaning patients did not experience severe side effects that outweighed the benefits. However, like any new treatment, some side effects may occur. Earlier trials suggested that GC012F might be a safe option for people with high-risk multiple myeloma, especially those eligible for a transplant.

Overall, the data so far suggests safety and effectiveness, but this trial continues to explore these aspects further. Understanding these findings can help prospective participants make an informed decision. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for multiple myeloma, which often involve chemotherapy and proteasome inhibitors, GC012F offers a new approach by utilizing CAR T-cell therapy. This innovative treatment involves reprogramming a patient's own T-cells to specifically target and destroy myeloma cells. Researchers are excited about GC012F because it has the potential to provide a more personalized and effective treatment, possibly leading to longer-lasting remission with just a single infusion. This approach also aims to reduce the side effects typically associated with traditional therapies.

What evidence suggests that this treatment might be an effective treatment for Multiple Myeloma?

Research has shown that GC012F (also known as AZD0120), a new therapy using modified immune cells, may help treat multiple myeloma, especially in patients unresponsive to other treatments. One study found that 22 patients who received GC012F had good control over their disease, and none experienced a severe immune reaction called cytokine release syndrome. Early results also suggest that GC012F is both effective and safe for patients with high-risk multiple myeloma. These findings offer hope that this therapy could benefit those whose multiple myeloma has returned or not responded to other treatments. ^{1 2 5 6 7}

Who Is on the Research Team?

Yingda Wen

Principal Investigator

Gracell Biopharmaceuticals, Inc.

Are You a Good Fit for This Trial?

Adults with relapsed/refractory Multiple Myeloma who have tried at least three treatment lines including a PI, IMiD, and an antiCD38 antibody. They must have measurable disease, good bone marrow and organ function, be over 18 years old with an ECOG status of 0 or 1. Exclusions include other cancers within the last two years (except certain skin cancers), severe heart issues, CNS involvement by myeloma, specific related diseases like POEMS syndrome or AL amyloidosis.

Inclusion Criteria

My bone marrow and organs are functioning well.

I am fully active or restricted in physically strenuous activity but can do light work.

Your medical records show that your disease has been getting worse according to specific criteria.

Exclusion Criteria

I have a history of severe heart muscle disease not caused by poor blood flow.

I had a stem cell transplant less than 6 months ago and have no GVHD.

My multiple myeloma has affected or is affecting my brain or spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1b Treatment

Evaluation of safety, tolerability, pharmacokinetics, and pharmacodynamics of GC012F (AZD0120) in subjects with relapsed/refractory Multiple Myeloma

4 weeks

1 infusion, multiple follow-up visits

Phase 2 Treatment

Evaluation of efficacy and further characterization of safety, pharmacodynamics, and immunogenicity of GC012F (AZD0120)

2 years

1 infusion, regular follow-up visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• GC012F

Trial Overview The trial is testing GC012F, a dual-targeting CAR T therapy aimed at CD19 and BCMA in patients with multiple myeloma that has come back or hasn't responded to treatment. It's an early-phase study where all participants receive the experimental therapy to evaluate its safety and effectiveness.

How Is the Trial Designed?

Group I: GC012F (AZD0120) Experimental Treatment 1 Intervention

GC012F (AZD0120) will be administrated in one infusion

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Gracell Biopharmaceuticals, Inc.

Lead Sponsor

Trials

2

Recruited

90+

Published Research Related to This Trial

CAR T cell therapies targeting BCMA have shown promising results in early clinical trials for treating multiple myeloma, indicating potential for long-lasting remissions.

However, these therapies are associated with significant toxicities, including cytokine release syndrome and neurotoxicity, highlighting the need for ongoing research to improve their safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cell immunotherapy for multiple myeloma: A review of current data and potential clinical applications. Susanibar Adaniya, SP., Cohen, AD., Garfall, AL.[2020]

A systematic review identified 27 clinical trials of CAR T cell therapies for relapsed/refractory multiple myeloma, showing promising short-term efficacy with low rates of severe toxicities.

Most trials focused on CAR T cells targeting B-cell maturation antigen (BCMA), indicating that while CAR T therapy is a hopeful treatment option, further research is needed to optimize its effectiveness and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging Targets and Cellular Therapy for Relapsed Refractory Multiple Myeloma: A Systematic Review. George, LL., Deshpande, SR., Cortese, MJ., et al.[2022]

In a phase I clinical trial involving 30 multiple myeloma patients, anti-BCMA CAR T cells showed favorable safety with no high-grade cytokine release syndrome and only one case of low-grade neurologic toxicity.

The treatment demonstrated significant efficacy, with 10 out of 15 patients with measurable disease achieving a partial response or better, and 4 patients converting to minimal residual disease-negative complete response, indicating strong antimyeloma activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-BCMA/CD19 CAR T Cells with Early Immunomodulatory Maintenance for Multiple Myeloma Responding to Initial or Later-Line Therapy. Garfall, AL., Cohen, AD., Susanibar-Adaniya, SP., et al.[2023]

BCMA CAR T-cell therapy has shown impressive response rates of 60% to 100% in patients with relapsed/refractory myeloma, indicating its potential as a highly effective treatment option.

While the therapy can lead to severe but reversible toxicities like cytokine release syndrome and neurotoxicity, ongoing studies aim to enhance its safety and efficacy through combinations with other treatments and gene editing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T Cells and Other Cellular Therapies for Multiple Myeloma: 2018 Update. Cohen, AD.[2019]

CAR T-cell therapy targeting B-cell maturation antigen (BCMA) has shown promising results in treating multiple myeloma, with high-quality responses observed in heavily pretreated patients, and ongoing Phase 3 trials are comparing its efficacy against standard treatments.

While CAR T-cell therapy can lead to sustained responses in some patients, most eventually relapse due to factors like loss of CAR T cells or antigen expression, prompting research into improving CAR design and safety measures, such as suicide gene systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy for multiple myeloma: state of the art and prospects. van de Donk, NWCJ., Usmani, SZ., Yong, K.[2021]

Chimeric antigen receptor (CAR)-T cell therapy shows promising efficacy and manageable toxicity in heavily pretreated multiple myeloma patients, with over 50 ongoing clinical trials exploring various CAR-T designs and targets.

The most effective CAR-T therapy so far targets B cell maturation antigen, but challenges remain, including the duration of response and the risk of prolonged cytopenia, necessitating further research to optimize treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of CAR-T cell therapies for multiple myeloma. Gagelmann, N., Riecken, K., Wolschke, C., et al.[2021]

CAR-T cell therapy, particularly targeting B-cell maturation antigen (BCMA), shows promising results in treating heavily pre-treated patients with multiple myeloma, indicating potential for long-term responses similar to those seen in B-cell malignancies like acute lymphoblastic leukemia.

Despite high response rates, challenges such as long-term outcomes, toxicities, and treatment resistance currently limit the widespread use of CAR-T therapies, highlighting the need for ongoing research to improve safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European Myeloma Network perspective on CAR T-Cell therapies for multiple myeloma. Bruno, B., Wäsch, R., Engelhardt, M., et al.[2021]

Chimeric antigen receptor (CAR) T-cell therapy shows great promise for treating relapsed/refractory multiple myeloma (RRMM), building on its success in other blood cancers like acute lymphocytic leukemia and diffuse large B-cell lymphoma.

The review highlights six potential target antigens for CAR T-cell therapy in multiple myeloma and discusses the safety profiles of existing CAR T-cell treatments, indicating a significant advancement in the management of this challenging disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current advances in chimeric antigen receptor T-cell therapy for refractory/relapsed multiple myeloma. Huang, H., Wu, HW., Hu, YX.[2020]

Chimeric antigen receptor (CAR)-modified T cell therapy has shown promising efficacy in treating refractory or relapsed multiple myeloma (MM) in both preclinical and clinical studies, indicating a potential new treatment avenue for this incurable disease.

The toxicities associated with CAR-T cell therapy are manageable, suggesting that this innovative approach could be a safe option for patients with MM, especially as research continues to identify effective targets and improve technologies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cell therapies for multiple myeloma. Wu, C., Zhang, L., Brockman, QR., et al.[2020]

The introduction of second-generation proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies has significantly improved survival rates for multiple myeloma patients, but many still relapse, highlighting the need for new therapies.

B-cell maturation antigen (BCMA)-targeted CAR T-cell therapy shows promise as a new treatment option for patients with multiple myeloma who are resistant to current standard therapies, offering a different mechanism of action to combat the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Cells in Multiple Myeloma Are Ready for Prime Time. Rodríguez-Otero, P., Prósper, F., Alfonso, A., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39052306

B-Cell Maturation Antigen/CD19 Dual-Targeting ... Results: Of 22 patients receiving GC012F treatment, 6 experienced mild to moderate cytokine release syndrome (grade 1-2) and none experienced ...

2. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/1022/502612/Updated-Results-of-a-Phase-I-Open-Label-Single-Arm

Updated Results of a Phase I Open-Label Single-Arm Study of ... High-risk (HR) newly-diagnosed multiple myeloma (NDMM) has poor outcomes with standard first-line therapies, even in transplant-eligible (TE) ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05850234

NCT05850234 | A Study of GC012F (AZD0120), a CAR T ... GC012F (AZD0120) is a BCMA/CD19 dual CAR product under investigation for the treatment of patients with RRMM. What is the study measuring? Primary Outcome ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.8005

Updated results of a phase I, open-label study of BCMA ... Furthermore, initial results showed that GC012F showed considerable efficacy and safety in high-risk transplant-eligible newly diagnosed MM pts ...

5. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2821602

B-Cell Maturation Antigen/CD19 Dual-Targeting ... This single-arm, open-label phase 1 cohort study examines the safety, patient health, and survival outcomes of GC012F in individuals with ...

6. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D8310C00001

A Phase Ib/II Study of AZD0120, Dual-Targeting CAR-T ... Phase II aims to evaluate the efficacy of AZD0120, and to further characterize the safety, pharmacodynamic effects, immunogenicity, and changes in health- ...

7. onclive.com onclive.com/view/gc012f-remains-safe-generates-durable-responses-in-relapsed-refractory-myeloma

GC012F Remains Safe, Generates Durable Responses in ... Previous data from the phase 1 study presented at the 2022 ASCO Annual Meeting showed that treatment with GC012F led to an ORR of 89.3% (n = 25/ ...