CART-ddBCMA for Multiple Myeloma

(iMMagine-1 Trial)

Not currently recruiting at 32 trial locations

Overseen By Clinical Information

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Kite, A Gilead Company

Must not be taking: Steroids, Immunosuppressants, Anticoagulants, others

Disqualifiers: Plasma cell leukemia, Active infection, CNS involvement, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new therapy called anitocabtagene-autoleucel (CART-ddBCMA) for individuals whose multiple myeloma has returned or not responded to treatment. The therapy targets and fights cancer cells using a special type of immune cell called CAR-T cells. It is specifically for those who have tried at least three different treatments, including certain drugs, and still show measurable signs of the disease. Individuals with this type of multiple myeloma who have not succeeded with various treatments might be suitable for this study. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group, offering a chance to benefit from a potentially effective new therapy.

Will I have to stop taking my current medications?

The trial requires that you stop any systemic treatment for multiple myeloma and high-dose steroid therapy at least 14 days before a specific procedure called leukapheresis. If you are on these medications, you will need to stop them before participating.

Is there any evidence suggesting that CART-ddBCMA is likely to be safe for humans?

Research has shown that anitocabtagene-autoleucel, also known as CART-ddBCMA, is safe for people with relapsed or refractory multiple myeloma. In earlier studies, patients tolerated this treatment well, achieving a 97% overall response rate.

The safety profile indicates that side effects are manageable and not severe for most patients. Previous trials have demonstrated significant and lasting effects, suggesting the treatment works well for its intended purpose without causing major harm.

Overall, existing evidence supports the safety of anitocabtagene-autoleucel in treating this condition. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple myeloma?

The treatment CART-ddBCMA is unique because it involves a new approach called CAR T-cell therapy, specifically engineered to target BCMA, a protein found on multiple myeloma cells. Unlike traditional treatments like chemotherapy or proteasome inhibitors, CART-ddBCMA uses a patient's own immune cells, which are modified to better recognize and attack cancer cells. Researchers are excited because this method can potentially provide a more precise and potent attack on the cancer, leading to longer-lasting remissions with fewer side effects.

What evidence suggests that CART-ddBCMA might be an effective treatment for multiple myeloma?

Research has shown that anitocabtagene autoleucel, a type of CAR-T cell therapy targeting BCMA, holds promise for treating relapsed or hard-to-treat multiple myeloma. In one study, 97% of patients experienced a reduction in cancer signs, known as an objective response. Furthermore, 76% of patients achieved a complete response, meaning their cancer became undetectable. Patients in previous trials tolerated the treatment well, with few serious side effects. These findings suggest that anitocabtagene autoleucel could be a strong option for those with challenging cases of multiple myeloma. ^{1 2 3 5 6}

Who Is on the Research Team?

Arcellx, Inc.

Principal Investigator

Arcellx, Inc.

Are You a Good Fit for This Trial?

Adults with relapsed or refractory multiple myeloma who have tried at least three prior treatments, including proteasome inhibitors, IMiDs, and anti-CD38 antibodies. They must show measurable disease signs, be in good physical condition (ECOG 0-1), have a life expectancy over 12 weeks, and proper organ function. Participants should not be pregnant or breastfeeding and must agree to use effective birth control for a year post-treatment.

Inclusion Criteria

My multiple myeloma has not responded to 3 types of treatments including a proteasome inhibitor, IMiD, and anti-CD38 antibody.

Documented measurable disease including at least one or more of the following criteria: Serum M-protein ≥1.0 g/dL, Urine M-protein ≥200 mg/24 hours, Involved serum free light chain ≥10 mg/dL with abnormal κ/λ ratio (i.e., >4:1 or <1:2), Eastern Cooperative Oncology Group (ECOG) performance status 0-1, Life expectancy >12 weeks

Adequate organ function defined as: Oxygen (O2) saturation ≥92% on room air, Left Ventricular Ejection Fraction (LVEF) ≥45% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan, Absolute neutrophil count (ANC) ≥1.0k/µl, platelet count (PLT) ≥50k/µl, Creatinine clearance ≥45 mL/min min (as determined by the Cockgroft-Gault equation) and not on dialysis, Aspartate transaminase (AST)/alanine transaminase (ALT) <3 x upper limits of normal (ULN), Total bilirubin <1.5 x ULN (allow 3x ULN for Gilbert's syndrome), Prothrombin time test (PTT), prothrombin time (PT)/international normalized ratio (INR) <1.5 x ULN, unless on a stable dose of anti-coagulant for a thromboembolic event (Subjects with any history of thromboembolic stroke; or history or Grade 2 (G2) or greater hemorrhage within one year are excluded), Resolution of adverse events (AEs) from any prior systemic anticancer therapy, radiotherapy, or surgery to Grade 1 or baseline (except G2 alopecia and G2 sensory neuropathy), Male and female participants of childbearing potential must agree to use highly effective methods of birth control through 12 months after the dose of study treatment, Willing to comply with and able to tolerate study procedures, including consent to participate in separate Long-term Safety Follow-up lasting up to 15 years per FDA guidance, Subject's leukapheresis product from non-mobilized cells is received and accepted for cell processing by manufacturing site. NOTE: Leukapheresis will be performed only after all other eligibility criteria are confirmed

Exclusion Criteria

I have or had plasma cell leukemia.

Treatment with the following therapies as specified below: Any prior systemic treatment for multiple myeloma within the 14 days prior to scheduled leukapheresis, Receiving high-dose (e.g., >10 mg prednisone or equivalent) systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to leukapheresis, Prior treatment with any gene therapy or gene-modified cellular immune-therapy, Prior B-cell maturation antigen (BCMA) directed therapy, Autologous stem cell transplantation within 3 months prior to leukapheresis, or any prior allogeneic stem cell transplantation, Subjects with solitary plasmacytomas without evidence of other measurable disease are excluded, History of allergy or hypersensitivity to study drug components. Subjects with a history of severe hypersensitivity reaction to dimethyl sulphoxide (DMSO) are excluded, Contraindication to fludarabine or cyclophosphamide, Severe or uncontrolled intercurrent illness or laboratory abnormalities including: Active bacterial, viral, or fungal infection requiring systemic treatment (isolated fever may not constitute active infection in and of itself, (e.g., related to disease), Symptomatic congestive heart failure (i.e., New York Heart Association stage III or IV), Unstable angina, arrhythmia, or myocardial infarction (MI) within 6 months prior to Screening, Significant pulmonary dysfunction, Uncontrolled thromboembolic events or recent severe hemorrhage (i.e., within one year), Any history of pulmonary embolism (PE) in the past 12 months or deep vein thrombosis (DVT) within three months of enrollment. Therapeutic dosing of anticoagulants (e.g., warfarin, low molecular weight heparin, Factor Xa inhibitors) is allowed for history of PE/DVT if greater than twelve and three months, respectively, from time of enrollment, and should be at a stable maintenance dose, Auto-immune disease requiring immunosuppressive therapy within the last 24 months, Seropositive for and with evidence of active hepatitis B or C infection at time of Screening, or HIV seropositive, Subjects with a history of hepatitis B but have received antiviral therapy and have non-detectable viral DNA are eligible, Subjects seropositive because of hepatitis B virus vaccine with no signs or active infection are eligible, Subjects who had hepatitis C but have received antiviral therapy and show no detectable hepatitis C virus (HCV) viral RNA are eligible, Active central nervous system (CNS) involvement by malignancy, Any sign of active or prior CNS pathology including but not limited to history of epilepsy, seizure, paresis, aphasia, stroke, subarachnoid hemorrhage or CNS bleed, severe brain injury, dementia, cerebellar disease, Parkinson's disease, organic brain syndrome or psychosis, Active malignancy not related to myeloma that has required therapy in the last 3 years or is not in complete remission. Exceptions to this criterion include successfully treated non-metastatic basal cell or squamous cell skin carcinoma, or prostate cancer that does not require therapy, Females who are pregnant or breastfeeding or females of childbearing potential not using an effective method of birth control, Subjects with any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in study (or full access to medical records) as written including follow up, the interpretation of data or place the subject at unacceptable risk, Any vaccine ≤ 6 weeks before leukapheresis and/or anticipation of the need for such a vaccine during the subject's participation in the study, Concurrent enrollment on another study using an investigational therapy for the treatment of RRMM

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Enrollment

Participants are enrolled and prepared for treatment

1-2 weeks

Pre-treatment

Participants receive lymphodepleting chemotherapy before CAR-T cell infusion

1 week

Treatment

Single infusion of anitocabtagene-autoleucel is administered

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and efficacy monthly for the first 6 months, then quarterly up to 2 years

24 months

Long-term follow-up

Long-term safety data collection for up to 15 years

15 years

What Are the Treatments Tested in This Trial?

Interventions

• CART-ddBCMA

Trial Overview The trial is testing CART-ddBCMA, which is a type of CAR-T cell therapy targeting BCMA on cancer cells. It's for patients whose multiple myeloma has returned after treatment or hasn't responded to standard therapies. The study will assess the safety and effectiveness of this new intervention.

How Is the Trial Designed?

Group I: anitocabtagene-autoleucel Experimental Treatment 1 Intervention

Single dose of 115±10 x 10e-6 CAR+ anitocabtagene-autoleucel cells infused intravenously

CART-ddBCMA is already approved in United States for the following indications:

Approved in United States as anitocabtagene-autoleucel for:

• Relapsed or refractory multiple myeloma

Who Is Running the Clinical Trial?

Kite, A Gilead Company

Lead Sponsor

Trials

45

Recruited

4,300+

Multiple Myeloma Research Foundation

Collaborator

Trials

11

Recruited

3,600+

Arcellx, Inc.

Industry Sponsor

Trials

5

Recruited

650+

Published Research Related to This Trial

The novel CAR T-cell therapy CART-ddBCMA targeting B-cell maturation antigen was well tolerated in a phase 1 study involving 13 patients with relapsed and refractory multiple myeloma, showing a favorable safety profile with manageable adverse events.

All patients responded to the treatment, with 75% achieving complete or stringent complete responses, and 89% of evaluable patients reaching minimal residual disease negativity after a median follow-up of 56 weeks, indicating durable efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of CART-ddBCMA for the treatment of subjects with relapsed and refractory multiple myeloma. Frigault, MJ., Bishop, MR., Rosenblatt, J., et al.[2023]

In a phase II trial involving 69 patients with relapsed or refractory multiple myeloma, the combination of anti-BCMA and anti-CD19 CAR T cells resulted in a high overall response rate of 92%, with 60% achieving a complete response.

The treatment demonstrated a median progression-free survival of 18.3 months and a manageable safety profile, although 95% of patients experienced cytokine release syndrome, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Follow-Up of Combination of B-Cell Maturation Antigen and CD19 Chimeric Antigen Receptor T Cells in Multiple Myeloma. Wang, Y., Cao, J., Gu, W., 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]

Ciltacabtagene autoleucel (cilta-cel) significantly improved progression-free survival in patients with lenalidomide-refractory multiple myeloma, with a median progression-free survival not reached in the cilta-cel group compared to 11.8 months in the standard-care group, based on a phase 3 trial with 419 participants.

The cilta-cel group also showed higher overall response rates (84.6% vs. 67.3%) and complete response rates (73.1% vs. 21.8%) compared to standard care, although most patients experienced grade 3 or 4 adverse events, including cytokine release syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma. San-Miguel, J., Dhakal, B., Yong, K., et al.[2023]

Ciltacabtagene autoleucel (cilta-cel) demonstrated a significantly higher overall response rate (84% vs. 28%) and longer progression-free survival in patients with relapsed/refractory multiple myeloma compared to standard non-CAR-T therapies, based on a comparison of 113 patients in the CARTITUDE-1 study and 190 patients from the MAMMOTH dataset.

In the modified intent-to-treat population, cilta-cel showed an even more impressive overall response rate of 96% compared to 30% in the MAMMOTH cohort, indicating its potential as a highly effective treatment option for patients who have exhausted other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Cilta-cel, an Anti-BCMA CAR-T Cell Therapy, Versus Conventional Treatment in Patients With Relapsed/Refractory Multiple Myeloma. Costa, LJ., Lin, Y., Cornell, RF., et al.[2022]

Ciltacabtagene autoleucel (cilta-cel) has been approved by the FDA as a fifth-line treatment option for patients with relapsed or refractory multiple myeloma, marking a significant advancement in therapy options for this challenging condition.

Cilta-cel is notable for being the second chimeric antigen receptor T-cell therapy targeting BCMA to receive regulatory approval within a year, highlighting the rapid development of innovative treatments in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cilta-cel OK'd for Multiple Myeloma. [2022]

In a study involving 50 primary multiple myeloma (MM) samples, all expressed B-cell maturation antigen (BCMA), and 78% also expressed TACI, suggesting that targeting both antigens could enhance treatment effectiveness.

The engineered APRIL-based CAR (ACAR) demonstrated significant tumor-killing ability against both BCMA and TACI expressing cells, achieving up to 72.9% killing of primary MM cells, and showed potential to control tumors even in the presence of BCMA-targeting antibodies, indicating a promising strategy to prevent tumor escape.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An APRIL-based chimeric antigen receptor for dual targeting of BCMA and TACI in multiple myeloma. Lee, L., Draper, B., Chaplin, N., et al.[2023]

Patients with multiple myeloma who do not respond to existing therapies have limited survival, but new treatments like CAR T-lymphocytes, bispecific antibodies, and antibody-drug conjugates are showing promise in early trials.

Idecabtagene vicleucel (ide cel) and belantamab mafodotin (belamaf) have been approved for use in relapsed/refractory multiple myeloma based on positive results from phase 2 studies, indicating their potential effectiveness in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T-cells, bispecific antibodies, and antibody-drug conjugates for multiple myeloma: An update. Lakshman, A., Kumar, SK.[2022]

Ciltacabtagene autoleucel (cilta-cel) demonstrated significantly better efficacy compared to physician's choice of treatment in patients with relapsed or refractory multiple myeloma, with a relative risk of 2.95 for overall response rate and 111.70 for complete response or better.

The study showed that cilta-cel also improved progression-free survival and overall survival, with hazard ratios of 0.24 and 0.21 respectively, indicating it could be a promising new treatment option for patients who have already been exposed to multiple therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Efficacy of Ciltacabtagene Autoleucel in CARTITUDE-1 vs Physician's Choice of Therapy in the Long-Term Follow-Up of POLLUX, CASTOR, and EQUULEUS Clinical Trials for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma. Weisel, K., Martin, T., Krishnan, A., et al.[2022]

B-cell maturation antigen (BCMA) CAR T cells are emerging as a highly effective treatment for multiple myeloma, showing promise for inclusion in first-line therapy based on clinical and preclinical data.

Advancements in patient stratification through genomic analysis and improvements in CAR T-cell manufacturing are enhancing early diagnosis, management of side effects, and overall access to this innovative treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Cell Therapy in Multiple Myeloma: Mission Accomplished? Rasche, L., Hudecek, M., Einsele, H.[2023]

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/4825/533294/Phase-1-Study-of-Anitocabtagene-Autoleucel-for-the

Phase 1 Study of Anitocabtagene Autoleucel for the Treatment ... Results: As of May 31, 2024, 40 pts were enrolled; 38 pts (95%) received anito-cel (32, DL1; 6, DL2) and were evaluable for safety and clinical ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9989524/

Phase 1 study of CART-ddBCMA for the treatment of subjects ... Results showed that CART-ddBCMA was well tolerated and demonstrated a favorable toxicity profile. Only 1 case of grade ≥3 cytokine release syndrome and 1 case ...

3. onclive.com onclive.com/view/anitocabtagene-autoleucel-elicits-deep-responses-in-relapsed-refractory-multiple-myeloma

Anitocabtagene Autoleucel Elicits Deep Responses in ... Anitocabtagene autoleucel achieved a 97% objective response rate in relapsed/refractory multiple myeloma, with a stringent complete response ...

4. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/1031/530531/Phase-2-Registrational-Study-of-Anitocabtagene

Phase 2 Registrational Study of Anitocabtagene Autoleucel for ... Phase 2 registrational study of anitocabtagene autoleucel for the treatment of patients with relapsed and/or refractory multiple myeloma.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265024016768

Multiple Myeloma MM-382 iMMagine-3: A Phase 3, ... In a Phase 1 study, anito-cel demonstrated an overall response rate of 100% including a 76% complete response (CR)/stringent CR (sCR) rate in 38 patients with ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07045909

Efficacy and Safety of Anitocabtagene Autoleucel in ... The goal of this clinical trial is to learn if anitocabtagene autoleucel following induction therapy works to treat adult participants with newly diagnosed ...