Evaluation of Minimal Residual Disease in Newly Diagnosed Transplant-Eligible Multiple Myeloma Patients Treated with Ixazomib, Lenalidomide, and Dexamethasone
- Trial ID
- 2024-517321-99-00
- Protocol
- IRd, NMSG#23/15
- Sponsor
- HUS-yhtymae
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this prospective phase II study is to evaluate the efficacy of the treatment protocol involving **ixazomib**, **lenalidomide**, and **dexamethasone** (IRd) in newly diagnosed, transplant-eligible patients with **multiple myeloma**. This evaluation is based on serological and bone marrow analyses, including the assessment of minimal residual disease (MRD) using multiparameter flow cytometry (MFC). Additionally, the study aims to assess the safety profile of IRd induction therapy followed by autologous stem cell transplantation (ASCT), IRd consolidation, and maintenance therapy with either IR or R. The clinical relevance of this study lies in its potential to improve treatment outcomes by effectively reducing MRD, which is a critical factor in predicting long-term remission and survival in multiple myeloma patients.
Participants
The clinical trial involves participants diagnosed with **multiple myeloma**, specifically targeting newly diagnosed, transplant-eligible individuals. The study population includes both male and female subjects aged between 18 and 70 years. Participants are required to have a symptomatic and measurable disease as per standard criteria, and they must not have received prior treatment for multiple myeloma, except for a specific dose of dexamethasone or comparable steroids and local radiotherapy for symptom control. The trial does not include a vulnerable population. Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2, and meet specific clinical laboratory criteria, including adequate neutrophil and platelet counts, liver function tests, and creatinine clearance. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as adherence to effective contraception methods are required for participants of childbearing potential, and all participants must be willing and able to comply with the study protocol. The selection process ensures that participants are capable of adhering to the study's visit schedule and other protocol requirements.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, and controlled study to evaluate the efficacy and safety of a treatment regimen for patients with **multiple myeloma**. The trial involves the administration of **ixazomib**, **lenalidomide**, and dexamethasone, collectively referred to as IRd, to newly diagnosed, transplant-eligible patients. The primary objective is to assess the minimal residual disease (MRD) using flow cytometry with a sensitivity of 10^-5. The trial is expected to span from January 2017 to May 2028, with participant involvement lasting up to three years.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, such as age, diagnosis, and laboratory values. Following the screening, participants will enter the treatment phase, which includes induction, consolidation, and maintenance therapy. Regular follow-up visits will be scheduled to monitor treatment response, safety, and MRD status. The end-of-study visit will conclude the participant's involvement, assessing the overall treatment outcomes and any long-term effects.
The expected length of participant involvement is approximately three years, with conditions for early termination including withdrawal of consent, adverse events, or failure to adhere to the study protocol. Participants must meet inclusion criteria, such as being between 18 and 70 years old, having symptomatic and measurable disease, and providing informed consent. Exclusion criteria are not specified in the provided data. The study aims to provide valuable insights into the treatment's efficacy and safety, contributing to the understanding of therapeutic strategies for multiple myeloma.
Treatment
The clinical trial involves the administration of several **experimental medications**. The primary experimental medication is **Revlimid**, which contains the active substance **lenalidomide**. It is available in hard capsule form with varying dosages of 5 mg, 10 mg, 15 mg, 20 mg, and 25 mg. The capsules are administered orally. The maximum daily dose for each variant corresponds to its respective dosage, with a treatment period of up to 3 months. The manufacturer of Revlimid is Bristol-Myers Squibb Pharma EEIG, and the medication is chemically derived.
Another experimental medication used in the trial is **NINLARO**, which contains the active substance **ixazomib citrate**. NINLARO is also provided in hard capsule form with a dosage of 4 mg. The administration route is oral, with a maximum daily dose of 4 mg and a total dose of 12 mg over a treatment period of 3 months. The manufacturer of NINLARO is Takeda Pharma A/S, and the substance is chemically derived. This medication is designated as an orphan drug.
Additionally, the trial includes the use of **IXAZOMIB** as a comparator treatment. IXAZOMIB is provided in capsule form and contains the active substance **ixazomib**. It is administered orally with a maximum daily dose of 4 mg, and the treatment period is up to 3 months. The substance is chemically derived and is also designated as an orphan drug.
Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen. The trial aims to assess the efficacy and safety of these treatments in newly diagnosed transplant-eligible patients.
Efficacy
Efficacy in this clinical trial will be assessed by evaluating the proportion of patients achieving undetectable minimal residual disease (MRD) with a sensitivity of 10-5 at any time during the protocol treatment. The primary endpoint focuses on the detection of MRD using flow cytometry, a method that allows for precise measurement of residual disease levels in patients undergoing treatment. This assessment will be conducted through serological and bone marrow analyses, which are integral to determining the efficacy of the treatment regimen comprising **ixazomib**, **lenalidomide**, and dexamethasone (IRd) for newly diagnosed transplant-eligible patients with multiple myeloma.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Newly diagnosed transplant eligible male or female multiple myeloma patients, 18-70 years of age, who have not received prior treatment for multiple myeloma 2. Symptomatic and measurable disease diagnosed by standard criteria; International Myeloma Working Group, CRAB and SLIM-CRAB (biomarker) criteria 3. Voluntary written informed consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care. 4. Female patients who: • Are postmenopausal for at least 1 year before the screening visit, OR • Are surgically sterile, OR • If they are of childbearing potential, fertile, agree to practice 2 effective methods of contraception (see 7.8 Pregnancy; acceptable contraception methods), at the same time, and agree to ongoing pregnancy testing and adhere to the guidelines of the lenalidomide pregnancy prevention program from the time of signing the informed consent form through 90 days after the last dose of study drug, OR Hospital District of Helsinki and Uusimaa/Helsinki University Hospital (HUS) Clinical Study Protocol [IISR-2015-101282-X16085] EudraCT 2015-004863 35 NMSG 23/15 Confidential 43 V8 05Mar2022 • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.) Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree to one of the following: • Agree to practice effective barrier contraception and adhere to the guidelines of the lenalidomide pregnancy prevention program during the entire study treatment period and through 90 days after the last dose of study drug, OR • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception. 4. Patients must have a diagnosis of a symptomatic multiple myeloma without any previous therapies except dexamethasone 160 mg dose, or comparable dose of other steroids, and local radiotherapy for symptom control 5. Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2. 6. Patients must meet the following clinical laboratory criteria: • Absolute neutrophil count (ANC) ³ 1,000/mm3 (≥ 1.0 x 109/L) and platelet count ³ 75,000/mm3 (75 x 109/L). Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment. • Total bilirubin £ 1.5 ´ the upper limit of the normal range (ULN). • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) £ 3 ´ ULN. • Calculated creatinine clearance ³ 30 mL/min (Cockcroft-Gault estimation of creatinine clearance (CRcl): CRcl (mL/min) = (140 - age) (weight [kg]) / 72 (serum creatinine [mg/dL]); for females, multiply by 0.85 (Cockcroft DW. 1976, Luke DR. 1990). 7. Patient must be willing and able to adhere to the study protocol visit schedule and other protocol requirements. 8. Negative pregnancy test at inclusion if applicable Hospital District
Exclusion Criteria
- Female patients who are lactating or have a positive serum pregnancy test during the screening period. 2. Major surgery within 14 days before enrollment. 3. Radiotherapy within 14 days before enrollment 4. Central nervous system involvement with multiple myeloma. 5. Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment. 6. Inability, unwillingness or contraindication to use thrombosis prophylaxis or antithrombotic therapy or herpes zoster prophylaxis 7. Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension (blood pressure without medication ≥ 200/120), uncontrolled cardiac arrhythmias (other than fibrillatio atriorum with adequate anticoagulation or superventricular or ventricular extrasystolia, symptomatic congestive heart failure (NYHA classification Appendix 14.7), unstable angina, or myocardial infarction within the past 6 months. 8. Systemic treatment, within 14 days before the first dose of ixazomib, strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John’s wort. 9. Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive. 10. Any serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to this protocol. 11. Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent. 12. Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib or lenalidomide including difficulty swallowing. Hospital District of Helsinki and Uusimaa/Helsinki University Hospital (HUS) Clinical Study Protocol [IISR-2015-101282-X16085] EudraCT 2015-004863 35 NMSG 23/15 Confidential 45 V8 05Mar2022 13. Diagnosed or treated for another malignancy within 5 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection. 14. Patient has Grade 1 polyneuropathy with pain or worse on clinical examination during the screening period. 15. Participation in other clinical trials, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial. 16. Patients that have previously been treated for multiple myeloma or smoldering myeloma with ixazomib or any other therapy, or participated in a study with ixazomib whether treated with ixazomib or not. 17. Primary plasma cell leukemia, POEMS syndrome, Waldenström disease, myelodysplastic syndrome or myeloproliferative disease 18. Systemic AL amyloidosis/primary amyloidosis or myeloma associated amyloidosis. 19. Allogeneic stem cell transplantation planned 20. Participants receiving any other investigational agents or received within 60 days
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Finland | Not Recruiting | 02 Jan 2017 | 45 |
 Lithuania | Not Recruiting | 02 Jan 2017 | 13 |
 Norway | Not Recruiting | 02 Jan 2017 | 33 |
 Sweden | Not Recruiting | 02 Jan 2017 | 29 |
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 10 mg hard capsules | Comparator | HARD CAPSULES | ORAL | 10 | 3 | PRD9264283 |
Revlimid 15 mg hard capsules | Comparator | HARD CAPSULES | ORAL | 15 | 3 | PRD9264282 |
Revlimid 20 mg hard capsules | Comparator | HARD CAPSULES | ORAL | 20 | 3 | PRD9264267 |
IXAZOMIB | Test | — | ORAL | 4 | 3 | SUB121332 |
NINLARO 4 mg hard capsules | Test | HARD CAPSULES | ORAL | 4 | 3 | PRD4535103 |
IXAZOMIB | Test | — | ORAL | 4 | 3 | SUB121332 |
Revlimid 25 mg hard capsules | Comparator | HARD CAPSULES | ORAL USE | 25 | 3 | PRD9264271 |
Revlimid 5 mg hard capsules | Comparator | HARD CAPSULES | ORAL | 5 | 3 | PRD9264284 |