Iberdomide + CC-99282 for Lymphoma

Recruiting at 55 trial locations

Overseen By BMS Study Connect Contact Center www.BMSStudyConnect.com

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Celgene

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: CNS involvement, HIV, Hepatitis B/C, others

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

Compensation: Varies

Number of Visits: Unknown

174 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase 1b study consisting of 2 parts: a dose escalation (Part 1) of CC-220 or CC-99282 added to the standard R-CHOP-21 regimen for first-line treatment of a-BCL. The dose escalation (Part 1) will consist of 2 parallel arms in combination with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP-21); CC-220 and R-CHOP-21 or CC-99282 and R-CHOP-21. Part 1 will be followed by a randomized dose expansion (Part 2) with CC-220 and/or CC-99282 at the Recommended Phase 2 Dose (RP2D) in combination with R-CHOP-21. A polatuzumab-R-CHP regimen in combination with CC-220 or CC-99282 will be explored with the addition of a new cohort only after the RP2D for the CC-220 and/or CC-99282 and R-CHOP-21 combination has been defined.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. However, it does exclude participants on chronic systemic immunosuppressive therapy or corticosteroids, which might suggest some restrictions. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Iberdomide + CC-99282 for Lymphoma?

Polatuzumab vedotin, a component of the treatment, has shown effectiveness in treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL) when combined with bendamustine and rituximab, achieving a complete response rate of 40% compared to 18% with bendamustine and rituximab alone. ^{1 2 3 4 5}

What safety data exists for the treatment involving polatuzumab vedotin in lymphoma?

Polatuzumab vedotin, when combined with other drugs like rituximab, cyclophosphamide, doxorubicin, and prednisone, has shown similar safety to standard treatments in lymphoma, with common side effects including peripheral neuropathy (nerve damage causing tingling or numbness) and cytopenias (low blood cell counts). ^{1 3 6 7 8}

What makes the drug Iberdomide + CC-99282 unique for treating lymphoma?

The combination of Iberdomide and CC-99282 for lymphoma is unique because it includes novel agents like Iberdomide, which modulates cereblon, a protein involved in immune response, and CC-99282, which is part of a new class of drugs. This combination is designed to enhance the immune system's ability to fight cancer cells, offering a potentially more effective treatment option compared to traditional therapies. ^{9 10 11 12 13}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

Adults over 18 with a specific type of untreated lymphoma (a-BCL) can join this trial. They must have certain blood and organ function levels, no serious health issues, and agree to pregnancy prevention measures if applicable. People with other lymphoma types, CNS involvement by lymphoma, significant medical conditions or infections like COVID-19, recent major surgery, inability to swallow tablets, HIV or active hepatitis B/C are excluded.

Inclusion Criteria

Participants must have the following laboratory values:

I am a woman who can become pregnant.

- Hemoglobin (Hb) ≥ 8 g/dL.

Exclusion Criteria

I have not had major surgery in the last 2 weeks or have recovered from its effects.

You are allergic to any part of the CHOP/CHP treatment.

You are allergic to thalidomide, pomalidomide, or lenalidomide.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Dose escalation of CC-220 or CC-99282 added to the standard R-CHOP-21 regimen for first-line treatment of aggressive B-cell lymphoma

6 cycles (each cycle is 21 days)

Randomized Dose Expansion

Randomized dose expansion with CC-220 and/or CC-99282 at the Recommended Phase 2 Dose (RP2D) in combination with R-CHOP-21

6 cycles (each cycle is 21 days)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• CC-220
• CC-99282
• Cyclophosphamide
• Doxorubicin
• Polatuzumab vedotin
• Prednisone
• Rituximab
• Vincristine

Trial Overview The study is testing the safety and effectiveness of two drugs (Iberdomide [CC-220] and CC-99282) combined with R-CHOP chemotherapy in treating lymphoma. It has two parts: first determining safe doses (dose escalation), then giving these doses to more people to see how well they work (dose expansion).

Participant Groups

Group I: Administration of CC-99282 with polatuzumab-R-CHP Experimental Treatment 6 Interventions

CC-99282 to be administered orally in combination with Polatuzumab vedotin, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (polatuzumab-R-CHP) for 6 cycles of treatment

Group II: Administration of CC-99282 with R-CHOP-21 Experimental Treatment 6 Interventions

CC-99282 to be administered orally in combination with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP-21) for 6 cycles of treatment

Group III: Administration of CC-220 with polatuzumab-R-CHP Experimental Treatment 6 Interventions

CC-220 to be administered orally in combination with Polatuzumab vedotin, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (polatuzumab-R-CHP) for 6 cycles of treatment

Group IV: Administration of CC-220 with R-CHOP-21 Experimental Treatment 6 Interventions

CC-220 to be administered orally in combination with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP-21) for 6 cycles of treatment

Who Is Running the Clinical Trial?

Celgene

Lead Sponsor

Trials

649

Recruited

130,000+

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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

Findings from Research

Polatuzumab vedotin, an antibody-drug conjugate targeting CD79b, has been approved for treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in patients who are ineligible for transplant, showing a complete response rate of 40% compared to 18% for standard treatment with bendamustine and rituximab (BR).

The most common side effects associated with polatuzumab vedotin treatment include cytopenias (a reduction in blood cells) and peripheral neuropathy, highlighting the need for monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin to treat relapsed or refractory diffuse large B-cell lymphoma, in combination with bendamustine plus rituximab. Amaya, ML., Jimeno, A., Kamdar, M.[2021]

Rituximab (RTX) is a widely used monoclonal antibody for treating diffuse large B-cell lymphoma, often combined with other drugs in the R-CHOP regimen, but some patients experience suboptimal responses or resistance.

New developments in CD20-targeting monoclonal antibodies, including second- and third-generation agents like ofatumumab and obinutumumab, are being actively researched to improve treatment outcomes for B-cell non-Hodgkin's lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel CD20 monoclonal antibodies for lymphoma therapy. Cang, S., Mukhi, N., Wang, K., et al.[2022]

In a phase 3 trial involving 879 patients with untreated intermediate-risk or high-risk diffuse large B-cell lymphoma (DLBCL), the modified regimen pola-R-CHP (which replaces vincristine with polatuzumab vedotin) showed a significantly higher progression-free survival rate at 2 years (76.7%) compared to the standard R-CHOP regimen (70.2%).

The overall survival rates at 2 years were similar between the pola-R-CHP and R-CHOP groups (88.7% vs. 88.6%), indicating that while pola-R-CHP may reduce the risk of disease progression, it does not significantly improve overall survival compared to the standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. Tilly, H., Morschhauser, F., Sehn, LH., et al.[2022]

In a study of patients with transplantation-ineligible relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), the combination of polatuzumab vedotin with bendamustine and rituximab (pola-BR) resulted in a significantly higher complete response (CR) rate of 40% compared to 17.5% with bendamustine and rituximab alone, indicating improved efficacy.

Patients receiving pola-BR also experienced longer progression-free survival (9.5 months vs. 3.7 months) and overall survival (12.4 months vs. 4.7 months), although there were higher rates of certain side effects like neutropenia and peripheral neuropathy, which were mostly manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma. Sehn, LH., Herrera, AF., Flowers, CR., et al.[2021]

Polatuzumab vedotin is an antibody-drug conjugate that has shown significant clinical activity and an acceptable safety profile in treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL), particularly when combined with anti-CD20 monoclonal antibodies and chemotherapy.

The recent POLARIX trial suggests that polatuzumab may also be effective in frontline treatment for DLBCL, potentially changing its role in managing patients who have not responded to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin in relapsed / refractory aggressive B-cell lymphoma. Varma, G., Wang, J., Diefenbach, C.[2022]

In the phase 3 POLARIX study, the combination of polatuzumab vedotin with rituximab and chemotherapy (Pola-R-CHP) significantly improved progression-free survival (PFS) in patients with untreated diffuse large B-cell lymphoma compared to the standard treatment R-CHOP, with a hazard ratio of 0.64 indicating a 36% reduction in the risk of disease progression.

The safety profile of Pola-R-CHP was comparable to R-CHOP, with similar rates of serious adverse events and peripheral neuropathy, suggesting that Pola-R-CHP is both effective and safe for patients in both the global and Asian populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin in previously untreated DLBCL: an Asia subpopulation analysis from the phase 3 POLARIX trial. Song, Y., Tilly, H., Rai, S., et al.[2023]

In pivotal study GO29365 involving patients with relapsed/refractory diffuse large B-cell lymphoma, polatuzumab vedotin (1.8 mg/kg) combined with bendamustine-rituximab showed a favorable risk/benefit profile, supporting its use for six cycles.

Supportive studies indicated that higher exposure to polatuzumab vedotin increased response rates but also raised the risk of side effects like peripheral neuropathy and anemia, suggesting that dosing should not fall below 1.8 mg/kg to maintain efficacy while managing safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure-safety and exposure-efficacy analyses of polatuzumab vedotin in patients with relapsed or refractory diffuse large B-cell lymphoma. Lu, T., Gibiansky, L., Li, X., et al.[2021]

Alpelisib (Piqray) is effective for treating advanced or metastatic breast cancer that is HR-positive, HER2-negative, and has PIK3CA mutations, targeting specific genetic alterations to improve treatment outcomes.

Polatuzumab vedotin-piiq (Polivy) is used for diffuse large B-cell lymphoma, while eculizumab (Soliris) is indicated for neuromyelitis optica spectrum disorder, highlighting the development of targeted therapies for specific cancer types and autoimmune conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmaceutical Approval Update. Choy, M.[2020]

Avadomide, when combined with obinutuzumab, demonstrated manageable toxicity in patients with relapsed or refractory non-Hodgkin lymphoma, with a recommended phase 2 dose established at 3.0 mg.

Although the study did not meet the prespecified threshold for activity, the preliminary antitumor effects suggest that this combination could be a promising chemotherapy-free treatment option for heavily pretreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avadomide plus obinutuzumab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (CC-122-NHL-001): a multicentre, dose escalation and expansion phase 1 study. Michot, JM., Bouabdallah, R., Vitolo, U., et al.[2020]

90Y-ibritumomab tiuxetan, a radioimmunoconjugate targeting CD20, demonstrated an overall response rate (ORR) of 80% in relapsed non-Hodgkin's lymphoma patients, significantly higher than the 44% ORR seen with rituximab alone.

In patients with low-grade non-Hodgkin's lymphoma, the response rate was even more impressive at 82%, indicating that 90Y-ibritumomab tiuxetan may be a more effective treatment option for this specific patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of ibritumomab tiuxetan radioimmunotherapy for patients with relapsed B-cell non-Hodgkin's lymphoma. Witzig, TE.[2016]

In a phase II trial involving 25 patients with diffuse large B-cell lymphoma (DLBCL) who were not candidates for aggressive treatment, (90)Y ibritumomab tiuxetan (90Y-IT) achieved an overall response rate of 36%, with 8 patients achieving a complete response.

The treatment demonstrated an acceptable safety profile, with significant thrombocytopenia in 65% of patients but no major bleeding events, indicating that (90)Y-IT can be a viable option for patients who cannot undergo more aggressive therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Yttrium-90 ibritumomab tiuxetan followed by rituximab maintenance as treatment for patients with diffuse large B-cell lymphoma are not candidates for autologous stem cell transplant. Arnason, JE., Luptakova, K., Rosenblatt, J., et al.[2016]

In a study of 40 patients with low-grade or follicular B-cell non-Hodgkin's lymphoma, the combination of Rituxan (Rituximab) and CHOP chemotherapy resulted in a high overall response rate of 95%, with 55% achieving complete remission.

The combination therapy showed promising safety, with common side effects being manageable, and it also indicated potential for clearing minimal residual disease, as evidenced by the conversion of the bcl-2 translocation from positive to negative in several patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. Czuczman, MS., Grillo-López, AJ., White, CA., et al.[2022]

Rituximab, a monoclonal antibody targeting CD20, has significantly improved treatment outcomes for patients with B-cell lymphoma, validating the use of immunotherapy in this field.

Newer anti-CD20 antibodies and immuno-drug-conjugates are being developed to enhance efficacy and safety, and to target other lymphoma types, indicating a promising direction for future lymphoma therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ongoing development of monoclonal antibodies and antibody drug-conjugates in lymphoma. Boyle, EM., Morschhauser, F.[2021]

References

1. Spain pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin to treat relapsed or refractory diffuse large B-cell lymphoma, in combination with bendamustine plus rituximab. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Novel CD20 monoclonal antibodies for lymphoma therapy. [2022]

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

Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. [2022]

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

Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin in relapsed / refractory aggressive B-cell lymphoma. [2022]

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

Polatuzumab vedotin in previously untreated DLBCL: an Asia subpopulation analysis from the phase 3 POLARIX trial. [2023]

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

Exposure-safety and exposure-efficacy analyses of polatuzumab vedotin in patients with relapsed or refractory diffuse large B-cell lymphoma. [2021]

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

Pharmaceutical Approval Update. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Avadomide plus obinutuzumab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (CC-122-NHL-001): a multicentre, dose escalation and expansion phase 1 study. [2020]

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

The use of ibritumomab tiuxetan radioimmunotherapy for patients with relapsed B-cell non-Hodgkin's lymphoma. [2016]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Yttrium-90 ibritumomab tiuxetan followed by rituximab maintenance as treatment for patients with diffuse large B-cell lymphoma are not candidates for autologous stem cell transplant. [2016]

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

Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. [2022]

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

Ongoing development of monoclonal antibodies and antibody drug-conjugates in lymphoma. [2021]