Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: C4 Therapeutics, Inc.
Must not be taking: Strong CYP3A modulators
Disqualifiers: CNS disease, Pneumonitis, Cardiac disease, others
No Placebo Group
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.
12345What 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.
12367Eligibility 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.
My lymphoma or myeloma is resistant to treatment and I can't use known effective treatments.
I am not pregnant, not breastfeeding, and meet the specific conditions.
I have had at least 3 treatments for myeloma, including 2 cycles of specific drugs.
I have been diagnosed with multiple myeloma and it can be measured.
I am a male and will use contraception during and after the study as required.
I have received treatment specific to my type of non-Hodgkin lymphoma.
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.
I am not taking any strong medications that affect liver enzymes.
I have not received a live vaccine in the last 4 weeks.
I have tested positive for Hepatitis B.
I have been diagnosed with HIV.
I have active inflammation in my lungs.
I have a condition affecting my brain or spinal cord.
I have moderate to severe numbness, tingling, or pain in my hands or feet.
Participant Groups
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.
8Treatment groups
Experimental Treatment
Group I: Phase 2: Arm 4 - CFT7455Experimental Treatment1 Intervention
Participants with r/r peripheral T-cell lymphoma (PTCL) treated with oral cemsidomide single agent
Group II: Phase 2: Arm 3 - cemsidomideExperimental Treatment1 Intervention
Participants with r/r mantle cell lymphoma (MCL) treated with oral CFT7455
Group III: Phase 2: Arm 2 - cemsidomide in combination with dexamethasoneExperimental Treatment2 Interventions
Participants with r/r MM treated with oral cemsidomide in combination with oral dexamethasone
Group IV: Phase 2: Arm 1 - cemsidomideExperimental Treatment1 Intervention
Participants with r/r MM will be treated with oral cemsidomide single agent
Group V: Phase 1: Arm C - cemsidomideExperimental Treatment1 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 dexamethasoneExperimental Treatment2 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 - cemsidomideExperimental Treatment1 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 - cemsidomideExperimental Treatment1 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.
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Colorado Blood Cancer Institute (Sarah Cannon Research Institute)Denver, CO
Mayo ClinicJacksonville, FL
Medical College of WisconsinMilwaukee, WI
University of California-San FranciscoSan Francisco, CA
More Trial Locations
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Who is running the clinical trial?
C4 Therapeutics, Inc.Lead Sponsor
References
The emerging role of lenalidomide in the management of lymphoid malignancies. [2021]Lenalidomide, a novel immunomodulatory drug (IMiD), is a promising therapeutic strategy for patients with relapsed/refractory chronic lymphocytic leukemia (CLL) and B-cell lymphomas. Biologically, the mechanisms responsible for lenalidomide activity are yet to be clearly defined. Based on preclinical models and early correlative studies conducted in parallel to clinical trials, lenalidomide has been found to enhance natural killer (NK)- and T-cell activity against tumor cells, alter the balance of pro- and anti-inflammatory cytokines in the tumor bed, inhibit angiogenesis, and, to a lesser degree, induce cell cycle arrest and apoptosis in cancer cells. Together, all of these biological effects appear to play a role in the activity observed in CLL or lymphoma patients treated with lenalidomide. Given the effect in NK- and T-cell function, lenalidomide is an alternative strategy to enhance the antitumor activity of monoclonal antibodies (mAbs). Clinical responses have been observed in patients with relapsed/refractory CLL, follicular lymphoma, small lymphocytic lymphoma, mantle cell lymphoma (MCL), and diffuse large B-cell lymphoma (DLBCL) treated with lenalidomide single agent. The favorable toxicity profile and route of administration made the use of lenalidomide an attractive therapy for certain types of patients (i.e. elderly, chemotherapy unfit, etc.). The erratic but serious incidence of tumor lysis syndrome and/or tumor flare reactions provides challenges in the incorporation of lenalidomide in the management of previously untreated CLL or CLL/lymphoma patients with bulky adenopathy. Correlative studies and/or retrospective analysis of lenalidomide-treated patients had identified several biomarkers associated with clinical endpoints in CLL (i.e. changes in tumor necrosis factor alpha [TNF-α] or vascular endothelial growth factor [VEGF] levels) or DLBCL (non-GCB phenotype) patients, but need to be validated. Early studies evaluating the efficacy and toxicity of lenalidomide in combination with rituximab in previously untreated indolent lymphoma are promising and warrant further study. In addition, the evaluation of lenalidomide in the maintenance setting or in combination with other target-specific agents (i.e. proteasome inhibitors) in aggressive lymphomas is being addressed in ongoing clinical trials. In summary, lenalidomide is emerging as a biologically active and novel agent in the treatment of B-cell neoplasms. Future translational and clinical studies will further define the role of lenalidomide in the management of de novo or relapsed/refractory CLL or B-cell lymphomas and identify the subset of patients most likely to gain clinical benefit.
Lenalidomide alone and in combination for chronic lymphocytic leukemia. [2021]Lenalidomide is a member of the immunomodulatory agents (IMiDs), and is currently approved for use in myelodysplastic syndromes and multiple myeloma. In chronic lymphocytic leukemia (CLL), lenalidomide has anti-tumor activity which appears distinct, both mechanistically and clinically, from that observed in the approved indications. Furthermore, lenalidomide leads to toxicities, such as tumor flare reaction and tumor lysis, even at low dosing, that is not anticipated with lenalidomide therapy in other disorders. This review will discuss the current understanding of the mechanisms of action of lenalidomide in CLL, lessons of administration learned from clinical trials in CLL to date, and the potential role of lenalidomide in CLL for the future.
Lenalidomide and chronic lymphocytic leukemia. [2021]Lenalidomide is an oral immunomodulatory drug used in multiple myeloma and myelodysplastic syndrome and most recently it has shown to be effective in the treatment of various lymphoproliferative disorders such as chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma. The mechanism of action of lenalidomide varies depending on the pathology, and in the case of CLL, it appears to primarily act by restoring the damaged mechanisms of tumour immunosurveillance. This review discusses the potential mechanism of action and efficacy of lenalidomide, alone or in combination, in treatment of CLL and its toxic effects such as tumor lysis syndrome (TLS) and tumor flare reaction (TFR), that make its management different from other hematologic malignancies.
Management of patients with chronic lymphocytic leukemia treated with lenalidomide. [2018]Lenalidomide is an immunomodulatory drug that has shown preliminary activity in the treatment of chronic lymphocytic leukemia (CLL). Much is known about the safety profile of lenalidomide from experience in other hematologic malignancies, such as myelodysplastic syndromes and multiple myeloma. In addition to the known adverse effects associated with lenalidomide (e.g., myelosuppression, rash, fatigue), some unique effects (e.g., tumor flare reactions, tumor lysis syndrome) have arisen during clinical studies of CLL. Typical signs of tumor flare reactions include early onset of painful enlargement of the lymph nodes or spleen, with or without low-grade fever, rash, and bone pain. Management may require nonsteroidal anti-inflammatory drugs or a short course of corticosteroids. Dose delays or reductions usually are not required for tumor flare reactions. Signs of tumor lysis syndrome may include shortness of breath, peripheral edema, generalized weakness, sweating, fever, and tachycardia. Untreated tumor lysis syndrome can result in renal impairment and congestive heart failure. Careful monitoring and appropriate management of treatment-related side effects can help ensure that patients with CLL achieve maximum therapeutic benefit from lenalidomide therapy.
Approaches to Managing Safety With Lenalidomide in Hematologic Malignancies. [2020]Lenalidomide is an oral immunomodulatory agent approved in relapsed multiple myeloma with dexamethasone, for transfusion-dependent anemia in myelodysplastic syndrome associated with deletion 5q, and in relapsed/progressive mantle cell lymphoma following bortezomib. In recent clinical trials, lenalidomide has shown promising activity in hematologic malignancies, including chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL). Starting doses and dosing schedules vary by malignancy, with lenalidomide started at a lower dose for CLL than for NHL or multiple myeloma. Certain adverse events (AEs) are common across tumor types (e.g., neutropenia, thrombocytopenia, fatigue), whereas others are more often associated with CLL patients (e.g., tumor lysis syndrome and tumor flare reaction). Effective management requires awareness of these differences as well as appropriate prophylaxis, monitoring, and treatment of AEs. This article reviews the efficacy and safety of lenalidomide in CLL and NHL, focusing on approaches for the advanced practitioner to improve patient quality of life through optimal management of side effects. With these steps, lenalidomide can be administered safely, at the best starting doses and with minimal dose interruptions or reductions across hematologic malignancies.
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]To present the final analysis, with a median follow-up of 8 years, of the LNH87-2 randomized study, which compares consolidative sequential chemotherapy (ifosfamide plus etoposide, asparaginase, and cytarabine) with high-dose therapy (HDT) using cyclophosphamide, carmustine, and etoposide (CBV regimen) followed by stem-cell transplantation in patients with aggressive non-Hodgkin's lymphoma in first complete remission after induction, focusing on high/intermediate- and high-risk patients identified by the age-adjusted international prognostic index.
Effect of a 2-hour infusion of 2-chlorodeoxyadenosine in the treatment of refractory or previously untreated Waldenström's macroglobulinemia. [2019]2-Chlorodeoxyadenosine (2-CdA) is a new purine analogue active in indolent lymphoid malignancies. In this retrospective study 22 patients with Waldenström's macroglobulinemia (MW) were treated with 2-CdA given in 2-h intravenous infusions. Nine of them were untreated and 13 relapsed or were refractory to previous therapeutic modalities with chlorambucil/prednisone (11 patients) or COP (2 patients). The patients were given 1-11 (median 4) courses of 2-CdA at the dose of 0.14 mg/kg daily in 2-h intravenous infusion for 5 consecutive days. The courses were repeated every 28-35 d. If severe myelosuppression or infection developed, 2-CdA therapy was stopped until the haematological parameters increased. The effectiveness of the treatment was evaluated after the 3 cycles and after completion of therapy. None of the patients has achieved complete response (CR) after 3 courses of treatment and only one (4.5%) has obtained CR after 5 courses. Partial response (PR) was achieved in 8 (36.4%) patients, giving an overall response rate of 40.9%. Ten further patients (45.4%) responded to the treatment with less than 50% decrease in monoclonal protein (defined as stabilisation). There was no significant difference between the response rate in previously pretreated (38.5%) and untreated (44.4%) patients (p>0.05). Mean observed decrease in monoclonal protein was 41%. In the group of 9 patients responding to 2-CdA treatment mean duration of response was 12 months (range 3-34). Myelosuppression was the most prominent side-effect. Neutropenia was present in 17 (77.3%) and thrombocytopenia in 7 (31.8%) patients. In 6 patients myelosuppression was the reason for treatment discontinuation after 1 or 2 courses without significant therapeutic effect. Seven patients died, including 4 from the responding group and all three non-responding patients. Treatment-related thrombocytopenia and fatal haemorrhage was the course of death in 1 patient. In conclusion, the results of our study show that 2-CdA given in 2-h infusions is an effective agent in WM and may be given on an outpatient basis. However, myelosuppression is frequent and the drug must be administered with caution.