CAR T Cells +/− Lenalidomide for Multiple Myeloma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

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

Compensation: Varies

Number of Visits: 4

Duration: Up to 7 days

20 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this phase I clinical trial is to test the safety of these CAR T cells in patients with myeloma. There are two parts of this study. Part 1 of the study consists of screening for BCMA, Lenalidomide assignment and cell collection. Part 2 of the study is treatment with modified CAR T cells.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on systemic steroids (except for adrenal replacement) within two weeks of cell collection.

What data supports the effectiveness of the treatment CAR T Cells +/− Lenalidomide for Multiple Myeloma?

Research shows that combining lenalidomide with anti-BCMA CAR T-cell therapy can be effective for patients with multiple myeloma who did not respond to previous treatments, achieving a significant response in some cases. Additionally, studies indicate that CAR T-cell therapies targeting BCMA can reduce tumor burden and improve survival in multiple myeloma models. ^{1 2 3 4 5}

What safety data exists for CAR T Cells with or without Lenalidomide in treating multiple myeloma?

CAR T cell treatments, with or without Lenalidomide, have shown some safety concerns, including cytokine release syndrome (a condition where the immune system releases too many proteins into the blood too quickly) and blood-related issues like low white blood cell counts. However, these side effects were generally manageable and reversible with treatment. ^{1 3 6 7 8}

How is the CAR T cell treatment with lenalidomide different for multiple myeloma?

This treatment combines CAR T cells, which are engineered immune cells targeting cancer, with lenalidomide, a drug that boosts immune function. The combination enhances the effectiveness of CAR T cells, especially in challenging environments, and has shown promising results in patients who did not respond to CAR T cells alone. ^{1 2 3 7 8}

Research Team

Sham Mailankody, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults over 18 with Multiple Myeloma, who've had at least two prior treatments including specific therapies (IMiD and PI), and have persistent or worsening disease. They must have adequate organ function and not be pregnant, without certain severe health conditions like heart issues, active infections, or other cancers needing treatment.

Inclusion Criteria

Your blood levels of hemoglobin, white blood cells, and platelets are within a certain range without needing extra blood or medication for at least 1 week.

I am 18 years old or older.

Your creatinine and bilirubin levels are not too high, and your liver enzymes (AST and ALT) are within a certain range.

Exclusion Criteria

I do not have any active cancer needing treatment except for skin cancer.

My heart's pumping ability is below normal.

I do not have HIV or active hepatitis B or C.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Cell Collection and Lenalidomide Assignment

Screening for BCMA, Lenalidomide assignment, and cell collection

2-4 weeks

Treatment

Participants receive treatment with modified CAR T cells

Up to 7 days

Up to 3 infusions

Follow-up

Participants are monitored for safety and effectiveness after treatment

36 months

Treatment Details

Interventions

• Cyclophosphamide
• EGFRt/BCMA-41BBz CAR T cell
• Lenalidomide

Trial Overview The study tests the safety of BCMA-targeted CAR T cells in treating myeloma. It has two parts: screening/assignment/cell collection and then treatment with modified CAR T cells. Some patients will also receive Lenalidomide to see if it improves outcomes.

Participant Groups

Group I: BCMA Targeted CAR T Cells with or without Lenalidomide Experimental Treatment 3 Interventions

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Juno Therapeutics, Inc.

Industry Sponsor

Trials

8

Recruited

810+

Juno Therapeutics, Inc., a Bristol-Myers Squibb Company

Industry Sponsor

Trials

19

Recruited

3,100+

Findings from Research

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]

Modified Vγ9Vδ2 T cells, engineered with a BCMA-specific CAR, showed strong ability to kill multiple myeloma cells while leaving normal cells unharmed, indicating a targeted and effective approach to treatment.

In a mouse model, treatment with these CAR-modified T cells, combined with Zometa, significantly reduced tumor burden and improved survival rates, suggesting promising potential for this therapy in human patients with multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vγ9Vδ2 T cells expressing a BCMA-Specific chimeric antigen receptor inhibit multiple myeloma xenograft growth. Zhang, X., Ng, YY., Du, Z., et al.[2022]

In a phase 1 study of 33 patients with relapsed or refractory multiple myeloma, the CAR T-cell therapy bb2121 demonstrated a high objective response rate of 85%, with 45% of patients achieving complete responses.

While bb2121 showed promising antitumor activity, it also had significant safety concerns, with 76% of patients experiencing cytokine release syndrome and 42% experiencing neurological toxic effects, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma. Raje, N., Berdeja, J., Lin, Y., et al.[2021]

In a study involving 16 patients with relapsed or refractory multiple myeloma, the bispecific CS1-BCMA CAR-T cells showed a high overall response rate of 81%, with 38% achieving a stringent complete response, indicating strong efficacy in targeting this challenging cancer.

The treatment had a manageable safety profile, with 38% of patients experiencing mild cytokine release syndrome and significant hematological adverse events, but no neurological toxicities were reported, suggesting a favorable safety outcome for this innovative therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific CS1-BCMA CAR-T cells are clinically active in relapsed or refractory multiple myeloma. Li, C., Xu, J., Luo, W., et al.[2023]

The study developed novel chimeric antigen receptors (CAR) targeting CS1 for treating multiple myeloma, showing that these CAR T cells effectively attack tumor cells in mice.

Combining lenalidomide with CS1 CAR T cells significantly enhanced their immune functions and antitumor activity, suggesting a promising approach for future clinical trials in treating relapsed multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide Enhances the Function of CS1 Chimeric Antigen Receptor-Redirected T Cells Against Multiple Myeloma. Wang, X., Walter, M., Urak, R., et al.[2023]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Lenalidomide enhances the efficacy of anti-BCMA CAR-T treatment in relapsed/refractory multiple myeloma: a case report and revies of the literature. [2023]

2. United States 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. [2022]

3. United States 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. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Vγ9Vδ2 T cells expressing a BCMA-Specific chimeric antigen receptor inhibit multiple myeloma xenograft growth. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Bispecific CS1-BCMA CAR-T cells are clinically active in relapsed or refractory multiple myeloma. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Anti-B-cell Maturation Antigen Chimeric Antigen Receptor T cell Function against Multiple Myeloma Is Enhanced in the Presence of Lenalidomide. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Lenalidomide Enhances the Function of CS1 Chimeric Antigen Receptor-Redirected T Cells Against Multiple Myeloma. [2023]