CAR-T Therapy for Multiple Myeloma

No longer recruiting at 15 trial locations

Overseen By Megan Scott

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Marcelo Pasquini, MD

Must be taking: Lenalidomide

Must not be taking: Anticoagulants, Corticosteroids

Disqualifiers: CNS involvement, Organ transplant, 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 2 Jurisdictions 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 bb2121 (also known as idecabtagene vicleucel or Abecma) for individuals with multiple myeloma, a type of blood cancer. The goal is to determine if bb2121, combined with lenalidomide, can enhance responses following a specific type of stem cell transplant. Eligible participants should have undergone a stem cell transplant within the past year and must currently be on a lenalidomide maintenance regimen. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not have received certain treatments like plasmapheresis, major surgery, or radiation therapy less than 14 days before enrolling. You can continue lenalidomide maintenance therapy.

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

Research has shown that the treatment bb2121, also known as idecabtagene vicleucel, has been tested for safety in patients with multiple myeloma. One study found that 74.2% of patients had a complete response, meaning their cancer was not detectable after treatment. This suggests the treatment can be effective and safe, as these results were observed over an average follow-up period of about 28 months.

In another study, 89% of patients responded to the treatment, with many showing significant improvement. This indicates that most participants tolerated the treatment well. While these results are encouraging, side effects can still occur, and each person's experience may differ.

The trial also includes lenalidomide, which previous studies have shown to improve response rates and extend survival in multiple myeloma patients when used with another drug, dexamethasone. Lenalidomide is generally well-tolerated, though some patients have reported a decreased appetite as a side effect.

Overall, bb2121 and lenalidomide have been studied for safety and effectiveness, with many patients showing positive responses. However, as with any treatment, risks may still be involved, and participants should discuss potential side effects with their healthcare provider. ^{1 2 3 4 5}

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

Researchers are excited about bb2121 for multiple myeloma because it represents a significant shift from traditional treatments like proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies. Unlike these current options, bb2121 is a CAR-T cell therapy that specifically targets the BCMA protein on myeloma cells, offering a more personalized and potentially more effective approach. This therapy involves reprogramming a patient's own immune cells to better recognize and attack cancer cells, which could lead to improved outcomes and longer-lasting remissions.

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

Research has shown that bb2121, also known as idecabtagene vicleucel, holds promise for treating multiple myeloma. In studies, it helped 89% of patients, with many experiencing a complete or significant reduction in cancer. On average, patients lived about 8.8 months without disease progression. In this trial, participants will receive a combination of bb2121 and Lenalidomide. Some studies have shown Lenalidomide to have a 55% response rate, helping extend the time patients live without disease progression. Together, these treatments have effectively managed multiple myeloma for patients with limited options. ^{1 2 6 7 8}

Who Is on the Research Team?

Sergio Giralt, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Marcelo C Pasquini, MD, MS

Principal Investigator

Medical College of Wisconsin

Alfred Garfall, MD

Principal Investigator

University of Pennsylvannia

Are You a Good Fit for This Trial?

Adults over 18 with symptomatic multiple myeloma who've had autologous hematopoietic cell transplant within the last year, are on a lenalidomide maintenance regimen, and have good organ function. They must not be pregnant or breastfeeding and agree to use two forms of birth control. Excluded are those with certain medical conditions, previous gene or BCMA-targeted therapies, uncontrolled infections, or unwillingness to follow study protocols.

Inclusion Criteria

Your blood clotting time is not too fast.

My kidney function, measured by creatinine clearance, is good.

My initial treatment for myeloma didn't fully clear the cancer.

Exclusion Criteria

You have had a previous allogeneic hematopoietic cell transplant.

I stopped taking lenalidomide permanently due to severe side effects.

My multiple myeloma does not produce detectable levels of M protein.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Leukapheresis and Manufacturing

Patients undergo leukapheresis for collection of autologous lymphocytes, which are sent to manufacturing facilities

3-4 weeks

Lymphodepleting Chemotherapy

Patients receive cyclophosphamide and fludarabine for 3 consecutive days

1 week

CAR T-cell Infusion

Infusion of BCMA CAR T-cells at a target dose of 450 x106 cells

1 day

Maintenance Therapy

Maintenance lenalidomide is initiated and continues until 12 months post CAR T-cell infusion

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• bb2121
• Lenalidomide

Trial Overview The trial is testing bb2121 CAR-T cells in patients with multiple myeloma post-autologous hematopoietic cell transplant. The goal is to see if this treatment can improve responses in patients already on lenalidomide maintenance therapy. It's a Phase II study where all participants receive the same intervention.

How Is the Trial Designed?

Group I: Lenalidomide and bb2121 Experimental Treatment 5 Interventions

Patients complete apheresis and proceed to lymphodepleting chemotherapy with cyclophosphamide 300mg/m\^2 and fludarabine 30mg/m\^2 for 3 consecutive days followed by the infusion of BCMA CAR T-cells at a target dose of 450 x10\^6 cells. Maintenance lenalidomide, starting at 5mg a day for 21 days of a 28-day cycle will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the patient reaches 12 months post CAR T-cell infusion and continue free of progression.

bb2121 is already approved in United States, European Union for the following indications:

Approved in United States as Abecma for:

• Relapsed or refractory multiple myeloma

Approved in European Union as Abecma for:

• Relapsed or refractory multiple myeloma

Who Is Running the Clinical Trial?

Marcelo Pasquini, MD

Lead Sponsor

Trials

1

Recruited

40+

National Marrow Donor Program

Collaborator

Trials

63

Recruited

202,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Blood and Marrow Transplant Clinical Trials Network

Collaborator

Trials

51

Recruited

14,600+

Celgene a wholly owned subsidiary of BMS

Collaborator

Trials

1

Recruited

40+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9972020/

Real‐world data on lenalidomide dosing and outcomes in ... The objective of our study was to understand the dosing, efficacy, and tolerability of lenalidomide among TI NDMM patients in the real‐world setting.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0959804924017647

Characteristics and outcomes in patients with lenalidomide ... Outcomes were suboptimal: 55 % response rate, 10-mo median PFS, and 28-mo median OS. •. New, effective therapies are needed for this difficult-to-treat ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5774211/

Final analysis of survival outcomes in the phase 3 FIRST ... Rd continuous significantly extended OS compared with MPT and resulted in comparable OS to that with Rd18 in patients with multiple myeloma.

4. esmoopen.com esmoopen.com/article/S2059-7029(25)01383-3/fulltext

A network meta-analysis of randomized clinical trials in ... Comparative efficacy of lenalidomide-free regimens in patients with relapsed/refractory multiple myeloma (RRMM) previously exposed to ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265025000229

Real-World Treatment Patterns and Outcomes in Patients ... We report population-based real-world data on patients aged ≥ 65 years, most (81%) with comorbidities, who have lenalidomide-refractory multiple myeloma.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3256976/

Safety and Efficacy of Lenalidomide in Relapsed or ... Combination lenalidomide and dexamethasone (Len+Dex) has been shown to increase response rates and prolong survival compared with dexamethasone alone.

7. sciencedirect.com sciencedirect.com/science/article/pii/S2152265022017529

Generic Lenalidomide Rivelime Versus Brand-name ... This study aimed to compare use of original brand-name lenalidomide (Revlimid®) vs. generic equivalent (Rivelime®) in terms of efficacy, safety and survival ...

8. myeloma.org myeloma.org/revlimid-lenalidomide

Revlimid (Lenalidomide) In the phase III FIRST clinical trial, 23% of the newly diagnosed patients experienced a decreased appetite. Of those, only 3% had weight loss or malnutrition.