Carfilzomib, Lenalidomide, and Dexamethasone in New Multiple Myeloma Patients
- Carfilzomib is an experimental anti-cancer drug that has not yet been approved for treating multiple myeloma. Lenalidomide is a drug that may stop tumor growth and help the immune system kill cancer cells. Dexamethasone is a drug that helps stop inflammation. It is sometimes used to treat (alone or with other drugs) certain types of cancer, especially multiple myeloma. This combination of drugs has not been tested in people with multiple myeloma. Researchers want to see whether it is safe and effective for this group.
- To test the effectiveness of combined carfilzomib, lenalidomide, and dexamethasone in treating multiple myeloma.
- People at least 18 years of age who have multiple myeloma that has not been treated.
- Participants will be screened with a medical history and physical exam. They will also have blood and urine tests, a bone marrow sample, and molecular imaging studies.
- Participants will have eight 28-day cycles of treatment. The combined study drugs will be given as tablets and injections. Those in the study will be monitored with frequent blood tests, bone marrow samples, and molecular imaging studies. In addition to current standard measures to determine clinical responses, molecular tests will be conducted to define evidence of minimal residual disease.
- After the first four cycles of therapy, those who are eligible for a stem cell transplant will have stem cells collected and stored for use if the cancer returns.
After stem cell collection, participants will have the second four treatment cycles.
-, If the disease has improved or is stable at the end of eight cycles, those in the study may have another 12 cycles of low-dose (maintenance) lenalidomide alone.
- Participants will have regular follow-up visits after the end of the study chemotherapy.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Carfilzomib, Lenalidomide, and Dexamethasone in Newly Diagnosed Multiple Myeloma: Clinical and Correlative Phase II Study|
- Evaluate toxicity [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
- Best Response [ Time Frame: 4 years ] [ Designated as safety issue: No ]
|Study Start Date:||July 2011|
|Estimated Study Completion Date:||September 2017|
|Estimated Primary Completion Date:||July 2016 (Final data collection date for primary outcome measure)|
Patients will receive 8 cycles of induction combination therapy of CRd. Patients achieving stable disease or better after 8 cycles of CRd will receive lenalidomide extended dosing (phase I) for 12 cycles. After 12 cycles, patients will have the option to continue extended dosing (phase II) for one additional year
Cycle 1: 20 mg/m2 IV infusion over 30 minutes on days 1 and 2, then 36 mg/m2 IV on days 8, 9, 15, and 16 Cycle 2-8: 36mg/ m2 IV infusion over 30 minutes on days 1, 2, 8, 9, 15, and 16Drug: Lenalidomide
Cycle 1: 25 mg oral days 2-21 of 28-day cycle Cycle 2 - 8: 25 mg oral days 1-21 of 28-day cycleDrug: Dexamethasone
Cycle 1: 20 mg oral or IV on days 2, 8, 9, 15, 16, 22, and 23 Cycle 2-4: 20 mg oral or IV on days 1, 2, 8, 9, 15, 16, 22, and 23 Cycle 5-8: 10 mg oral or IV on days 1, 2, 8, 9, 15, 16, 22, and 23
- Multiple myeloma (MM) is an incurable plasma cell neoplasm with a median survival of 3-4 years.
- Novel agent combinations with proteasome inhibitors demonstrate improved response rates while increasing survival in MM patients.
- A common debilitating side effect of the proteasome inhibitor bortezomib is neuropathy.
- Carfilzomib is a new proteasome inhibitor with potent anti-MM effects and decreased peripheral neuropathy
-Evaluate toxicity, including peripheral neuropathy, of carfilzomib, lenalidomide, and dexamethasone (CRd) in untreated MM patients
- Newly diagnosed patients with histologically confirmed multiple myeloma
- Age greater than or equal to 18 years
- Creatinine Clearance (CrCl) greater than or equal to 60 ml/min. CrCl will be calculated using the Cockcroft- Gault method. If the calculated CrCl based on Cockcroft-Gault method is < 60 mL/min, patient will have a 24 hr urine collection to measure CrCl. The measured CrCl must also be greater than or equal to 60 ml/min.
- Without serious co-morbidity that would interfere with receipt of CRd
- Absolute neutrophil count (ANC) greater than or equal to 1.0 K/uL, hemoglobin greater than or equal to 8 g/dL, and platelet count greater than or equal to 75 K/uL
- Adequate hepatic function, with bilirubin less than 1.5 x the ULN, and AST and ALT less than 3.0 x ULN
- Single arm, single stage phase II trial of combination therapy (carfilzomib, lenalidomide, and dexamethasone) for untreated multiple myeloma patients with an early stopping rule for toxicity
- Patients will receive 8 cycles of induction combination therapy of CRd
- Each cycle consists of 28-days
- After 4 cycles of therapy, transplant eligible patients will undergo stem cell collection
- Patients achieving stable disease or better after 8 cycles of CRd will receive lenalidomide extended dosing (phase I) for 12 cycles. After 12 cycles, patients will have the option to continue extended dosing (phase II) for one additional year.
- Patients will have routine blood work with SPEP and free light chains monthly
- Pre- and post-treatment bone marrow biopsies will be obtained for confirmation of diagnosis and correlative studies
- Patients will also undergo evaluation for minimal residual disease at regular interval time points, using multi-parametric flow cytometry and FDG PET-CT
- A single stage phase II design will be employed, with an early stopping rule. Unless 4 or more patients in the first 20 have Grade 3 or higher neurologic toxicity in the first 2 completed cycles, a total of 45 evaluable patients will be enrolled in this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01402284
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Mark J Roschewski, M.D.||National Cancer Institute (NCI)|