Ide-cel Combination Therapy for Multiple Myeloma

(KarMMa-7 Trial)

No longer recruiting at 41 trial locations

Overseen By First line of the email MUST contain NCT # and Site #.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Celgene

Must be taking: Immunomodulatory agents

Must not be taking: Anticoagulants

Disqualifiers: Plasma cell leukemia, Amyloidosis, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for people with multiple myeloma, a type of blood cancer that has returned or is difficult to treat. It examines the effectiveness of a drug called bb2121 (also known as Ide-cel) when combined with other medications. The trial consists of two parts: one with bb2121 and CC-220, and another with bb2121 and BMS-986405, though the second part is no longer enrolling. Individuals who have tried several other treatments for multiple myeloma and still have the disease might be suitable candidates for this trial. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering a chance to explore new treatment options.

Do I have to stop taking my current medications for the trial?

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 to get specific guidance based on your situation.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the treatment bb2121, when combined with other drugs, is generally safe. Studies have found that bb2121, a type of CAR T-cell therapy, is usually well-tolerated by patients with multiple myeloma, meaning most people do not experience severe side effects.

One study found that using bb2121 with CC-220 (also known as iberdomide) had a safety profile similar to earlier research, indicating that combining these treatments does not cause unexpected problems. Iberdomide, when used with dexamethasone, was also found to be safe for patients who have tried many other treatments.

For the combination of bb2121 with BMS-986405, the focus remains on the safety of bb2121 itself. Previous research shows that bb2121 is safe and effective for people who have not responded to other treatments.

As this clinical trial is in its early stages, the main goal is to determine the right dose and monitor for any safety issues. Researchers closely observe participants' reactions to these combinations to ensure safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for multiple myeloma because they use a unique approach involving CAR-T cell therapy. BB2121, the study drug, harnesses the power of genetically engineered T cells to specifically target and destroy cancer cells. This is different from traditional treatments like chemotherapy and stem cell transplants, which affect both cancerous and healthy cells. In Arm A, BB2121 is combined with CC-220, potentially enhancing its effectiveness by modulating the immune system. Arm B pairs BB2121 with BMS-986405 (JSMD194), though enrollment for this arm is closed. This innovative approach has the potential to provide more targeted and effective treatment options for patients with multiple myeloma.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

Research has shown that bb2121, also known as Ide-cel, yields promising results for treating multiple myeloma, a type of blood cancer. In one study, Ide-cel helped 73% of patients, with 33% showing no detectable signs of cancer afterward. This trial will test one arm combining Ide-cel with CC-220, also known as iberdomide, which has significantly reduced the number of remaining cancer cells. Another arm will test Ide-cel with BMS-986405. These combinations suggest potential benefits for patients whose multiple myeloma has returned or not responded to other treatments. ^{1 2 3 4 5}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

This trial is for adults with relapsed or refractory multiple myeloma (R/RMM) who've had at least one prior treatment. They should have shown some response to previous treatments and currently show disease progression. Good physical condition (ECOG 0-1) is required, but those with certain blood conditions, severe liver issues, recent bleeding events or specific past treatments like gene therapy are excluded.

Inclusion Criteria

I have undergone at least 3 treatments for multiple myeloma.

I have responded positively to at least one prior treatment.

I have been diagnosed with multiple myeloma and it can be measured.

Exclusion Criteria

I have a specific blood cancer type, not the common multiple myeloma.

If you have any of the following issues in your blood, kidney function, liver function, or clotting, or if you have certain lung or previous treatment problems, you may not be able to participate in this study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Finding (Phase 1)

Participants receive bb2121 in combination with other therapies to determine the recommended Phase 2 dose

Up to 28 days

Multiple visits for dose limiting toxicity evaluation

Dose Expansion (Phase 2)

Participants receive bb2121 in combination with other therapies to evaluate safety and efficacy

Up to 24 months

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 24 months

What Are the Treatments Tested in This Trial?

Interventions

• BB2121
• BMS-986405
• Bortezomib
• CC-220
• Dexamethasone
• Pomalidomide

Trial Overview The study tests bb2121 combined with other drugs in two arms: Arm A pairs it with CC-220 (with/without dexamethasone), while Arm B uses BMS-986405. It's a phase 1/2 trial aiming to find the right doses and expand testing based on safety and effectiveness results from earlier phases.

How Is the Trial Designed?

Group I: Arm B- bb2121 in combination with BMS-986405 (JSMD194) Experimental Treatment 2 Interventions

* bb2121 will be administered at a target dose of 450 x 10\^6 CAR+T cells. The combination agent will be administered during Month 1 starting from the day of bb2121 infusion * Enrollment is closed for this Arm

Group II: Arm A- bb2121 in combination with CC-220 (± low-dose dexamethasone) Experimental Treatment 2 Interventions

bb2121 will be administered at a target dose of 450 x 10\^6 CAR+T cells. The combination agent will be administered at different doses and/ or schedules, depending on dose limiting toxicity (DLT) evaluation.

Who Is Running the Clinical Trial?

Celgene

Lead Sponsor

Trials

649

Recruited

130,000+

Top Products

>- **Revlimid (lenalidomide)**: Multiple myeloma, myelodysplastic syndromes, and mantle cell lymphoma treatment. - **Pomalyst (pomalidomide)**: Relapsed/refractory multiple myeloma treatment. - **Otezla (apremilast)**: Psoriatic arthritis treatment. - **Thalomid (thalidomide)**: Erythema nodosum leprosum and multiple myeloma treatment.

Jay Backstrom

Celgene

Chief Medical Officer since 2016

MD

Mark Alles

Celgene

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0006497121067252

Clinical KarMMa-7, a Phase 1/2, Dose-Finding and ... Long-term results from the pivotal phase 2 KarMMa study showed ide-cel induced an overall response rate (ORR) of 73% (33% complete response [CR] ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04855136

NCT04855136 | Safety and Efficacy of bb2121 (Ide-cel) ... This is a global, open-label, multi-arm, multi-cohort, multi-center, phase 1/2 study to determine the safety, tolerability, efficacy, PK of bb2121 in ...

3. bmsclinicaltrials.com bmsclinicaltrials.com/us/en/clinical-trials/NCT04855136

Trial ID BB2121-MM-007 | NCT04855136 - BMS Clinical Trials This is a global, open-label, multi-arm, multi-cohort, multi-center, phase 1/2 study to determine the safety, tolerability, efficacy, PK of bb2121 in ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10121830/

BCMA-Directed CAR T-Cells: Early Results and Future ... Efficacy Outcomes and Characteristics of Patients with Multiple Myeloma (MM) Who Achieved Sustained Minimal Residual Disease Negativity after Treatment with ...

5. mayo.edu mayo.edu/research/clinical-trials/cls-20519543

Safety and Efficacy of bb2121 (Ide-cel) Combinations in ... The purpose of this study is to determine the safety and effectiveness of bb2121 (Ide-Cel) combinations in subjects with relapsed/refractory ...