Phase II Multicenter Study of Carfilzomib, Lenalidomide, and Dexamethasone Regimens in Newly Diagnosed Multiple Myeloma Patients Eligible for Autologous Transplant
- Trial ID
- 2024-516630-35-01
- Protocol
- 2024-516630-35-00
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of the combination of Carfilzomib and dexamethasone with either cyclophosphamide or lenalidomide in achieving at least a very good partial response (VGPR) after four cycles of induction treatment in newly diagnosed multiple myeloma patients eligible for autologous stem cell transplantation (ASCT). This is clinically relevant as achieving a VGPR is associated with improved outcomes and progression-free survival in multiple myeloma patients.
Secondary objectives include:
- Determining the stringent complete response (sCR) rate after complete induction/consolidation therapy.
- Assessing progression-free survival in the three induction/consolidation arms.
- Evaluating Minimal Residual Disease (MRD) negativity rate and sustained MRD.
- Assessing overall response and safety in the induction/consolidation and maintenance arms.
- Determining time to next therapy, time to progression, progression-free survival 2, and overall survival.
- Evaluating the duration of response (DOR) and success of stem cell harvest.
- Exploring tumor response and outcomes in subgroups with different prognostic factors.
Participants
The clinical trial involves participants diagnosed with **newly diagnosed multiple myeloma** who are eligible for autologous transplant. The study population includes both male and female subjects aged 18 years and older, with a specific focus on individuals under 65 years of age. Participants are required to have a Karnofsky performance status of at least 60% and meet specific laboratory criteria, including platelet count and neutrophil count thresholds. The trial does not include a vulnerable population. Participants must have a life expectancy of at least three months and agree to use acceptable methods of contraception. The sponsor has not provided information regarding the total number of participants in the study. Lifestyle considerations such as diet and physical activity are not specified in the available data.
Plans and Procedures
The clinical trial is a **randomized**, open-label, phase II study designed to evaluate the efficacy and safety of different combinations of **carfilzomib** in patients with newly diagnosed **multiple myeloma** eligible for autologous transplantation. The trial involves three treatment arms: carfilzomib with cyclophosphamide and dexamethasone, carfilzomib with **lenalidomide** and dexamethasone, and a continuous treatment with carfilzomib, lenalidomide, and dexamethasone without transplantation. The study aims to assess the very good partial response (VGPR) or better after four cycles of induction treatment and to determine progression-free survival in the maintenance arms.
The trial is expected to run until March 31, 2026, with participant involvement lasting up to 72 weeks, depending on the treatment arm. The study includes several key visits: an initial screening visit to confirm eligibility based on criteria such as age, disease status, and laboratory values; regular follow-up visits to monitor treatment response and safety; and an end-of-study visit to assess final outcomes. Participants may be withdrawn from the study early if they experience unacceptable toxicity, withdraw consent, or if the investigator deems it necessary for their safety.
Inclusion criteria require participants to be 18 years or older, with a confirmed diagnosis of multiple myeloma based on standard CRAB criteria, and eligible for autologous stem cell transplantation. Exclusion criteria are not specified in the provided data. The primary endpoint focuses on the VGPR rate at cycle 4, while secondary endpoints include the stringent complete response rate and progression-free survival across the treatment arms. The trial is not classified as low intervention and is conducted under the authorization of relevant regulatory bodies.
Treatment
The clinical trial involves the administration of several experimental medications, primarily focusing on the treatment of **multiple myeloma**. The first experimental medication is **Revlimid** (lenalidomide), available in various dosages: 2.5 mg, 5 mg, 10 mg, and 25 mg, all in the form of hard capsules. These capsules are administered orally. The maximum daily doses for these formulations are 2.5 mg, 5 mg, 10 mg, and 25 mg, respectively, with a maximum treatment period of 72 weeks for the 2.5 mg, 5 mg, and 10 mg doses, and 12 weeks for the 25 mg dose. The total maximum dose amounts are 3780 mg, 7560 mg, 15120 mg, and 6300 mg, respectively. The active substance, lenalidomide, is of chemical origin and is manufactured by Bristol-Myers Squibb Pharma EEIG.
Another experimental medication used in the trial is **Kyprolis** (carfilzomib), which is provided as a 60 mg powder for solution for infusion. This medication is administered intravenously. The maximum daily dose is 36 mg/m², with a total maximum dose amount of 13024 mg/m² over a treatment period of 32 weeks. Carfilzomib is also of chemical origin and is produced by Amgen Europe B.V. This medication is designated as an orphan drug, indicating its use in the treatment of a rare condition.
In addition to the experimental medications, the trial includes non-experimental treatments such as **cyclophosphamide** and **dexamethasone**, which are standard-of-care therapies used in combination with the experimental drugs. These treatments are part of the induction and consolidation phases of the study. The trial aims to evaluate the efficacy of these combinations in achieving at least a very good partial response in newly diagnosed multiple myeloma patients eligible for autologous transplantation. Participant compliance with the dosing schedules is monitored throughout the study to ensure adherence to the treatment protocols.
Efficacy
Efficacy in this clinical trial will be assessed by evaluating the response rates and progression-free survival in patients with newly diagnosed **Multiple Myeloma** (MM) eligible for autologous transplantation. The primary efficacy endpoint is the rate of very good partial response (VGPR) or better, including stringent complete response (sCR) and complete response (CR), after four cycles of induction treatment. This assessment will be conducted in three treatment arms, utilizing the criteria established by the International Myeloma Working Group.
Secondary efficacy endpoints include determining the sCR rate in the three arms following complete induction and consolidation therapy, which involves induction, autologous stem cell transplantation (ASCT), and consolidation for the transplant arms, and after 12 cycles in the long treatment arm. Additionally, progression-free survival will be evaluated in both the maintenance and induction/consolidation arms. These efficacy parameters will be measured and analyzed at specified timepoints throughout the trial to ensure comprehensive assessment of the treatment's impact on disease progression and patient outcomes.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Age ≥ 18 years Newly diagnosed MM based on standard CRAB criteria (see appendix B). Patient < 65 years* eligible for ASCT. Patient has measurable disease according to IMWG criteria. Patient has given voluntary written informed consent. Patient agrees to use acceptable methods for contraception. Patient has a Karnofsky performance status ≥ 60% (see appendix G). Pretreatment clinical laboratory values within 30 days of enrollment: Platelet count ≥75 x 109/L (≥50 x 109 /L if myeloma involvement in the bone marrow is > 50%) Absolute neutrophil count (ANC) ≥ 1 x 109/L without the use of growth factors Corrected serum calcium ≤14 mg/dL (3.5 mmol/L) Alanine transaminase (ALT): ≤ 3 x the ULN Aspartate transaminase (AST): ≤ 3 x the ULN Total bilirubin: ≤ 2 x the ULN Calculated or measured creatinine clearance: ≥ 30 mL/minute. LVEF ≥ 40%. 2-D transthoracic echocardiogram (ECHO) is the preferred method of evaluation. Multigated Acquisition Scan (MUGA) is acceptable if ECHO is not available *until the day before the 66th birthday Life expectancy ≥ 3 months
Exclusion Criteria
- Previous treatment with anti-myeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid < to the equivalent of dexamethasone 40 mg/day for 4 days) Patients with non-secretory MM unless serum free-light chains are present and the ratio is abnormal or a plasmocytoma with minimum largest diameters of > 2 cm Patients ineligible for autologous transplantation Pregnant or lactating females Presence of: Clinical active infectious hepatitis type A, B, C or HIV Acute active infection requiring antibiotics or infiltrative pulmonary disease Myocardial infarction or unstable angina ≤ 4 months or other clinically significant heart disease Peripheral neuropathy or neuropathic pain grade 2 or higher, as defined by National Cancer Institute Common Toxicity Criteria (NCI CTC) 4.0 (Appendix A) Known history of allergy to Captisol ® (a cyclodextrin derivative used to solubilize carfilzomib) Contraindication to any of the required drugs or supportive treatments Invasive malignancy within the past 3 years Serious medical condition, laboratory abnormality or psychiatric illness that prevented the subject from the enrollment or place the subject at unacceptable risk.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Italy | Not Recruiting | 19 Sept 2015 | 477 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Revlimid 25 mg hard capsules | Test | HARD CAPSULES | ORAL USE | 25 | 12 | PRD9264271 |
Revlimid 5 mg hard capsules | Test | HARD CAPSULES | ORAL USE | 5 | 72 | PRD9264284 |
Revlimid 10 mg hard capsules | Test | HARD CAPSULES | ORAL USE | 10 | 72 | PRD9264283 |
Kyprolis 60 mg powder for solution for infusion | Test | POWDER FOR SOLUTION FOR INFUSION | INTRAVENOUS USE | 36 | 32 | PRD3374183 |
Revlimid 2.5 mg hard capsules | Test | HARD CAPSULES | ORAL | 2.5 | 72 | PRD9264293 |