CFT7455 for Lymphoma

Not currently recruiting at 14 trial locations

Overseen By Chief Medical officer

Age: 18+

Sex: Any

Trial Phase: Phase 1

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new oral medication, cemsidomide (also known as CFT7455), for individuals with certain blood cancers, specifically Non-Hodgkin's Lymphoma (NHL) and Multiple Myeloma (MM), that have not responded to other treatments. Researchers aim to understand how the body processes the drug and its impact on these cancers, sometimes combining it with dexamethasone for Multiple Myeloma. Individuals with relapsed or treatment-resistant NHL or MM, who have already tried several other treatments, might be suitable for this study. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new medication.

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.

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

Research has shown that cemsidomide, also known as CFT7455, is generally safe. In one study, when administered alone, most side effects were mild to moderate, such as nausea and tiredness, while more serious side effects were less common.

When combined with dexamethasone, a steroid often used in cancer treatment, cemsidomide remained generally safe. The side effects mirrored those seen with cemsidomide alone, suggesting that adding dexamethasone does not significantly increase the risk of serious side effects.

Overall, early results from these studies indicate that cemsidomide, both alone and with dexamethasone, is generally well-tolerated by patients. Further studies will continue to monitor its safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about cemsidomide, especially for treating relapsed or refractory multiple myeloma (r/r MM) and non-Hodgkin lymphoma (r/r NHL), because it offers a fresh approach. Unlike standard treatments like chemotherapy, which can be quite harsh and non-specific, cemsidomide works as a targeted therapy that selectively degrades specific proteins essential for cancer cell survival. This could mean fewer side effects and more precise action against the cancer. Additionally, when combined with dexamethasone, cemsidomide has the potential to enhance the treatment's effectiveness, providing a promising new option for patients who haven't responded well to existing therapies.

What evidence suggests that this trial's treatments could be effective for Non-Hodgkin's Lymphoma and Multiple Myeloma?

Research shows that CFT7455, also known as cemsidomide, may help treat certain blood cancers. In this trial, participants with relapsed or refractory non-Hodgkin's lymphoma (NHL) or multiple myeloma (MM) will receive cemsidomide as a single agent in various arms. For those with multiple myeloma, some trial arms will combine cemsidomide with dexamethasone (a type of steroid). Studies have shown that combining cemsidomide with dexamethasone led to a positive response in up to 50% of participants at higher doses, meaning that half of the participants saw their cancer reduce. These results suggest that cemsidomide could be a strong option for those with relapsed or hard-to-treat lymphoma and multiple myeloma. ^{1 2 3 4 6}

Who Is on the Research Team?

Michelle Mahler, MD

Principal Investigator

C4 Therapeutics, Inc.

Adam Crystal, MD

Principal Investigator

C4 Therapeutics, Inc.

Are You a Good Fit for This Trial?

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

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

I have had at least 3 treatments for myeloma, including 2 cycles of specific drugs.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

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

Group IV: 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 V: 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 VI: 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 VII: 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+

Published Research Related to This Trial

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 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 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]

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]

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]

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]

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]

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/467/531143/Initial-Results-of-a-Phase-1-First-in-Human-Study

Initial Results of a Phase 1 First-in-Human Study of ... Methods: CFT7455-1101 (NCT04756726) is an open-label, phase 1/2, multi-center, first-in-human study evaluating safety, efficacy, ...

2. c4therapeutics.com c4therapeutics.com/wp-content/uploads/CFT7455-ASH-2024-NHL-Oral_FINAL.pdf

Cemsidomide (CFT7455) Background *CFT7455 administered as 14 days on/14 days off in a 28-day cycle; 3 patients at 75µg are excluded as dose escalation meeting has not occurred as of cut-off ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124032142

Initial Results of a Phase 1 First-in-Human Study ... Methods: CFT7455-1101 (NCT04756726) is an open-label, phase 1/2, multi-center, first-in-human study evaluating safety, efficacy, pharmacokinetics (PK) and ...

4. c4therapeutics.com c4therapeutics.com/wp-content/uploads/CFT7455-ASH-Trial-in-Progress-Poster-Presentation.pdf

A Phase 1 Study of CFT7455, a Novel Degrader of IKZF1/3, ... (MCL), and peripheral T-cell lymphoma (PTCL), demonstrated greater activity with CFT7455 than pomalidomide. (Figures 2-5). Figure 2: Potent Anticancer Activity ...

5. sparkcures.com sparkcures.com/trial/1124/nct04756726

Multiple Myeloma Support + Trials Study to Assess the Safety and Tolerability of CFT7455 in Relapsed/Refractory Non-Hodgkin's Lymphoma or Multiple Myeloma. Am I Eligible? Resources. Overview.

6. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04756726/

Clinical Trial: NCT04756726 The purpose of this study is to characterize the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of CFT7455 ...