CFT7455 for Lymphoma

Recruiting at 13 trial locations

Overseen By Chief Medical officer

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: C4 Therapeutics, Inc.

Must not be taking: Strong CYP3A modulators

Disqualifiers: CNS disease, Pneumonitis, Cardiac disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days for Phase 1, up to 6 months for Phase 2

224 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to characterize the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of oral cemsidomide (also known as CFT7455) administered at different dosages in subjects with Relapsed/Refractory (r/r) Non-Hodgkin's Lymphoma (NHL) or Multiple Myeloma (MM). Cemsidomide may be administered as a single agent and, in MM only, in combination with oral dexamethasone.

Will I have to stop taking my current medications?

The trial requires that participants stop taking strong CYP3A modulators (certain drugs that affect how the body processes medications) and inhibitors of MDR1 and BCRP before starting the study drug. These must be stopped 5 half-lives or 14 days before the first dose, depending on the type of medication.

What is known about the safety of CFT7455 (Cemsidomide) in humans?

The safety of lenalidomide, a drug similar to CFT7455, has been studied in various blood cancers. Common side effects include fatigue, low blood cell counts, and skin rash, while more serious effects like tumor lysis syndrome (a condition where cancer cells break down rapidly) and tumor flare reactions (painful swelling of lymph nodes) have been observed, especially in chronic lymphocytic leukemia. ^{1 2 3 4 5}

What makes the drug CFT7455 unique for treating lymphoma?

CFT7455, also known as Cemsidomide, is unique because it is a novel drug that may work differently from existing treatments by potentially enhancing the body's immune response against lymphoma cells. This could involve mechanisms similar to lenalidomide, which boosts natural killer and T-cell activity, offering a new approach for patients who may not respond well to standard therapies. ^{1 2 3 6 7}

Research Team

Michelle Mahler, MD

Principal Investigator

C4 Therapeutics, Inc.

Adam Crystal, MD

Principal Investigator

C4 Therapeutics, Inc.

Eligibility Criteria

Adults with relapsed/refractory Non-Hodgkin's Lymphoma or Multiple Myeloma who've had specific prior treatments can join. They must have measurable disease, not be pregnant or planning to conceive, and agree to contraception. Exclusions include active pneumonitis, CNS disease, recent radiotherapy, HIV/Hepatitis B/C infection, certain other cancers within 3 years.

Inclusion Criteria

I am 18 years old or older.

I am not pregnant, not breastfeeding, and meet the specific conditions.

My myeloma did not respond or got worse within 2 months after my last treatment.

Exclusion Criteria

I have no other cancers that have worsened or needed treatment in the last 3 years.

I have a specific blood or bone marrow condition.

You have tested positive for hepatitis C (HCV) infection, regardless of the amount of virus in your body.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral cemsidomide, with or without dexamethasone, to determine safety, tolerability, and antitumor activity

28 days for Phase 1, up to 6 months for Phase 2

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days after the last dose for Phase 1, up to 6 months for Phase 2

Treatment Details

Interventions

• CFT7455
• Dexamethasone Oral

Trial Overview The trial is testing the safety and effectiveness of CFT7455 alone or combined with oral dexamethasone in different dosing schedules for those with certain types of blood cancer that haven't responded well to previous treatments.

Participant Groups

Group I: Phase 2: Arm 4 - CFT7455 Experimental Treatment 1 Intervention

Participants with r/r peripheral T-cell lymphoma (PTCL) treated with oral cemsidomide single agent

Group II: Phase 2: Arm 3 - cemsidomide Experimental Treatment 1 Intervention

Participants with r/r mantle cell lymphoma (MCL) treated with oral CFT7455

Group III: Phase 2: Arm 2 - cemsidomide in combination with dexamethasone Experimental Treatment 2 Interventions

Participants with r/r MM treated with oral cemsidomide in combination with oral dexamethasone

Group IV: Phase 2: Arm 1 - cemsidomide Experimental Treatment 1 Intervention

Participants with r/r MM will be treated with oral cemsidomide single agent

Group V: Phase 1: Arm C - cemsidomide Experimental Treatment 1 Intervention

Participants with r/r NHL will be treated with escalating doses of oral cemsidomide single agent administered according to different dosing schedules in each cohort

Group VI: Phase 1: Arm B2 - cemsidomide in combination with dexamethasone Experimental Treatment 2 Interventions

Participants with r/r MM will be treated with escalating doses of oral cemsidomide in combination with a fixed dose of oral dexamethasone in each cohort

Group VII: Phase 1: Arm B1 - cemsidomide Experimental Treatment 1 Intervention

Participants with r/r MM will be treated with escalating doses of oral cemsidomide as a single agent administered at different dosages and dosing schedules in each cohort, until the determination of maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) or Sponsor discretion.

Group VIII: Phase 1: Arm A - cemsidomide Experimental Treatment 1 Intervention

Participants with r/r NHL or r/r MM will be treated with oral cemsidomide as a single agent administered at different dosages and dosing schedules.

Who Is Running the Clinical Trial?

C4 Therapeutics, Inc.

Lead Sponsor

Trials

3

Recruited

480+

Findings from Research

Lenalidomide enhances the immune response against tumor cells by boosting the activity of natural killer (NK) and T-cells, and it has shown clinical responses in patients with various types of B-cell lymphomas and relapsed/refractory chronic lymphocytic leukemia (CLL).

While lenalidomide has a favorable safety profile and is particularly suitable for elderly or chemotherapy-unfit patients, there are risks of serious side effects like tumor lysis syndrome, which complicate its use in certain patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The emerging role of lenalidomide in the management of lymphoid malignancies. Hernandez-Ilizaliturri, FJ., Batoo, SA.[2021]

Lenalidomide shows distinct anti-tumor activity in chronic lymphocytic leukemia (CLL) compared to its approved uses in myelodysplastic syndromes and multiple myeloma, indicating a unique mechanism of action in this type of cancer.

The use of lenalidomide in CLL can lead to specific toxicities, such as tumor flare reactions and tumor lysis, even at low doses, which are not typically seen in its other approved indications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide alone and in combination for chronic lymphocytic leukemia. Chen, CI.[2021]

Lenalidomide is effective in treating chronic lymphocytic leukemia (CLL) by restoring the body's ability to detect and fight tumors, which is crucial for effective immunotherapy.

While lenalidomide shows promise in CLL treatment, it can cause specific toxic effects like tumor lysis syndrome (TLS) and tumor flare reaction (TFR), requiring careful management compared to other blood cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide and chronic lymphocytic leukemia. González-Rodríguez, AP., Payer, AR., Acebes-Huerta, A., et al.[2021]

Lenalidomide shows promise as a treatment for chronic lymphocytic leukemia (CLL), with a known safety profile from its use in other blood cancers, but it can cause unique side effects like tumor flare reactions and tumor lysis syndrome.

Effective management of these side effects, including monitoring for symptoms and using medications like nonsteroidal anti-inflammatory drugs or corticosteroids, is crucial to help patients maximize the benefits of lenalidomide therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of patients with chronic lymphocytic leukemia treated with lenalidomide. Miller, KC., Musial, L., Whitworth, A., et al.[2018]

Lenalidomide is an effective oral treatment for various hematologic malignancies, including chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), with different starting doses based on the type of cancer.

Common side effects like neutropenia and thrombocytopenia can be managed effectively with proper monitoring and prophylaxis, allowing for safer administration and improved patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Approaches to Managing Safety With Lenalidomide in Hematologic Malignancies. Blumel, S., Broadway-Duren, J.[2020]

In a study of 916 patients with aggressive non-Hodgkin's lymphoma, high-dose therapy (HDT) followed by stem-cell transplantation showed superior outcomes compared to sequential chemotherapy, with an 8-year disease-free survival rate of 55% versus 39%.

The 8-year overall survival rate was also significantly better in the HDT group at 64%, compared to 49% in the sequential chemotherapy group, indicating that HDT is more effective for higher-risk patients who achieve complete remission after initial treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival benefit of high-dose therapy in poor-risk aggressive non-Hodgkin's lymphoma: final analysis of the prospective LNH87-2 protocol--a groupe d'Etude des lymphomes de l'Adulte study. Haioun, C., Lepage, E., Gisselbrecht, C., et al.[2022]

In a study of 22 patients with Waldenström's macroglobulinemia treated with 2-Chlorodeoxyadenosine (2-CdA), the overall response rate was 40.9%, with partial responses in 36.4% of patients, indicating that 2-CdA can be an effective treatment option for this condition.

Myelosuppression was a significant side effect, affecting 77.3% of patients with neutropenia and leading to treatment discontinuation in some cases, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of a 2-hour infusion of 2-chlorodeoxyadenosine in the treatment of refractory or previously untreated Waldenström's macroglobulinemia. Hellmann, A., Lewandowski, K., Zaucha, JM., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

The emerging role of lenalidomide in the management of lymphoid malignancies. [2021]

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

Lenalidomide alone and in combination for chronic lymphocytic leukemia. [2021]

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

Lenalidomide and chronic lymphocytic leukemia. [2021]

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

Management of patients with chronic lymphocytic leukemia treated with lenalidomide. [2018]

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

Approaches to Managing Safety With Lenalidomide in Hematologic Malignancies. [2020]

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

Survival benefit of high-dose therapy in poor-risk aggressive non-Hodgkin's lymphoma: final analysis of the prospective LNH87-2 protocol--a groupe d'Etude des lymphomes de l'Adulte study. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Effect of a 2-hour infusion of 2-chlorodeoxyadenosine in the treatment of refractory or previously untreated Waldenström's macroglobulinemia. [2019]