A Phase 1/2 interventional study of carfilzomib, lenalidomide plus dexamethasone and carfilzomib, lenalidomide plus dexamethasone in Multiple Myeloma, sponsored by University of Michigan Rogel Cancer Center. Completed at 4 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-01-30.
Sponsored by University of Michigan Rogel Cancer Center · Phase 1/2, Interventional, and Health services research
This study is designed to evaluate the safety and to determine the maximum tolerated dose of carfilzomib + lenalidomide in combination with dexamethasone in newly diagnosed Multiple Myeloma patients who have not received treatment.
During the Phase I portion of this clinical trial, the dose of Revlimid® and carfilzomib will be increased until the best and safest amount (or dose) is identified in combination with standard doses of Revlimid® and dexamethasone. "Investigational" means that the drug combination is still being studied and that research doctors are trying to find out more about it such as the safest dose to use, the side effects it may cause and how effective the Revlimid® and carfilzomib and dexamethasone investigational combination is for treating newly diagnosed multiple myeloma. In this clinical trial we are looking for the highest dose of the combination that can be given safely and see how well it works as a combination in newly diagnosed patients.
The drug, carfilzomib, has not yet been approved by the FDA (U.S. Food and Drug Administration). Revlimid® and Dexamethasone have been approved by the FDA. The drugs have not been approved in this combination for use for your type of cancer or any other type of cancer. Carfilzomib is being researched to treat multiple myeloma. Dexamethasone is commonly used, either alone, or in combination with other drugs, to treat multiple myeloma. Revlimid® is currently approved by the US FDA in combination with dexamethasone for the treatment of patients with multiple myeloma who have received at least 1 prior therapy.
After the Phase I clinical trial defines the safest doses of Revlimid® and carfilzomib and dexamethasone that can be taken together, the research study will move on to its second portion, a Phase II clinical trial. The Phase II portion of the clinical trial will test the clinical effectiveness of the best dose combination of the three drugs.
3,712 studies on the registry are indexed under Multiple Myeloma; 752 are open to participants now.
This study's enrollment of 53 is above the median of 41 across 2,965 interventional studies indexed under Multiple Myeloma.
Browse Multiple Myeloma studies →University of Michigan Rogel Cancer Center is the lead sponsor of 322 studies on the registry; 47 are open to participants now.
Of its 46 completed or terminated interventional studies of FDA-regulated products, 31 (67%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Measurable disease, per IMWG (International Myeloma Working Group) criteria (>= one of the following) within the past 4 weeks:
Exclusion Criteria
Patient must not have been previously treated with any prior systemic therapy for the treatment of multiple myeloma
Phase I: carfilzomib will be taken with a combination of lenalidomide plus dexamethasone in a series of escalating dosages to determine the maximum tolerated dose level Phase II: carfilzomib will be given at the MTD established in the Phase I portion of the study
Drug: carfilzomib, lenalidomide plus dexamethasone
Drug pages: Carfilzomib · Lenalidomide · Dexamethasone
Phase I: Carfilzomib will be administered at the dosage assigned for the subject's cohort as an IV infusion on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle for Cycles 1 - 8 (induction) and on Days 1, 2, 15, and 16 of a 28-day cycle for Cycles 9+ (maintenance). Lenalidomide will be administered PO daily at 25 mg on Days 1- 21 of the 28-day cycle for Cycles 1 - 8+. Dexamethasone 40 mg will be administered PO or IV between 30 minutes and 4 hours preceding the carfilzomib push.
Drug pages: Carfilzomib · Lenalidomide · Dexamethasone
Phase II: Carfilzomib will be administered at the Maximum Tolerated Dose (MTD) established in Phase I as an IV infusion on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle for Cycles 1 - 8 (induction) and on Days 1, 2, 15, and 16 of a 28-day cycle for Cycles 9+ (maintenance). Lenalidomide will be administered PO daily at 25 mg on Days 1- 21 of the 28-day cycle for Cycles 1 - 8+. Dexamethasone will be administered PO or IV between 30 minutes and 4 hours preceding the carfilzomib push on Days 1, 8, 15, and 22 as follows: Cycles 1-4: 40 mg; Cycles 5-8: 20 mg; and Cycles 9 and higher: 10 mg.
The Maximum Tolerated Dose (MTD) of Carfilzomib
Determine the MTD of Carfilzomib when combined with Lenalidomide and Dexamethasone. The estimated time to determine the MTD is 6 months.
Time frame: 6 Months
The Percentage of Patients That Achieve a Response to Treatment
The percentage of patients that achieve at least a sCR (Stringent Complete Response), at least a VGPR (Very Good Partial Response) and at least a PR (Partial Response) will be determined. sCR is defined as: * Negative immunofixation on the serum and urine and * Disappearance of any soft tissue plasmacytomas and * \< 5% plasma cells in bone marrow and * Normal SFLC ratio and * Absence of clonal cells in bone marrow VGPR is defined as: * Serum and urine M-protein detectable by immunofixation but not on electrophoresis or * ≥ 90% reduction in serum M-component with urine M-component \< 100 mg per 24 hours PR is defined as: * ≥ 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥ 90% or to \< 200 mg per 24 hours * If present at baseline, a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required
Time frame: 4 Months After Treatment Start
The Percentage of Patients Alive Without Progression
The Progression Free Survival (PFS) rate will be determined at 12 and 24 months post treatment. Progressive Disease (PD) is defined as an increase of greater than or equal to 25% from lowest response level in serum M-component and/ or urine M-component and/ or the difference between involved or uninvolved SFLC levels and/ or bone marrow % plasma cells. PD may also be the development of new bone lesions or soft tissue plasmacytomas or the increase in size of existing lesions. PD may also be the development of hypercalcemia.
Time frame: 12 Months and 24 Months Post Treatment
| Milestone | Dose Escalation Cohort 1 | Dose Escalation Cohort 2 | Dose Escalation Cohort 3 |
|---|---|---|---|
| Started | 4 | 13 | 18 |
| Completed | 4 | 13 | 18 |
| Not completed | 0 | 0 | 0 |
| Milestone | Dose Escalation Cohort 1 | Dose Escalation Cohort 2 | Dose Escalation Cohort 3 |
|---|---|---|---|
| Started | 0 | 0 | 18 |
| Completed | 0 | 0 | 18 |
| Not completed | 0 | 0 | 0 |
Determine the MTD of Carfilzomib when combined with Lenalidomide and Dexamethasone. The estimated time to determine the MTD is 6 months.
| mg/m^2 | Carfilzomib, Lenalidomide w/Dexamethasone |
|---|---|
| The Maximum Tolerated Dose (MTD) of Carfilzomib | 36 |
The Progression Free Survival (PFS) rate will be determined at 12 and 24 months post treatment. Progressive Disease (PD) is defined as an increase of greater than or equal to 25% from lowest response level in serum M-component and/ or urine M-component and/ or the difference between involved or uninvolved SFLC levels and/ or bone marrow % plasma cells. PD may also be the development of new bone lesions or soft tissue plasmacytomas or the increase in size of existing lesions. PD may also be the development of hypercalcemia.
| percentage of patients | Carfilzomib, Lenalidomide w/Dexamethasone |
|---|---|
| Percentage of Patients Without Progression at 12 m | 97 |
| Percentage of Patients Without Progression at 24 m | 92 |
The percentage of patients that achieve at least a sCR (Stringent Complete Response), at least a VGPR (Very Good Partial Response) and at least a PR (Partial Response) will be determined. sCR is defined as: * Negative immunofixation on the serum and urine and * Disappearance of any soft tissue plasmacytomas and * \< 5% plasma cells in bone marrow and * Normal SFLC ratio and * Absence of clonal cells in bone marrow VGPR is defined as: * Serum and urine M-protein detectable by immunofixation but not on electrophoresis or * ≥ 90% reduction in serum M-component with urine M-component \< 100 mg per 24 hours PR is defined as: * ≥ 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥ 90% or to \< 200 mg per 24 hours * If present at baseline, a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required
| percentage of patients | Carfilzomib, Lenalidomide w/Dexamethasone |
|---|---|
| % of patients that achieve at least a sCR | 42 |
| % of patients that achieve at least a VGPR | 81 |
| % of patients that achieve at least a PR | 98 |
Collected over All Adverse Events (AEs) that occurred after the subject signed consent were documented.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Carfilzomib, Lenalidomide w/Dexamethasone | — | 23/53 (43.4%) | 53/53 (100%) |
| Event | Carfilzomib, Lenalidomide w/Dexamethasone |
|---|---|
| PneumoniaInfections and infestations | 4/53 |
| Urinary Tract InfectionInfections and infestations | 3/53 |
| Acute Renal FailureRenal and urinary disorders | 2/53 |
| DyspneaRespiratory, thoracic and mediastinal disorders | 2/53 |
| HyperglycemiaMetabolism and nutrition disorders | 2/53 |
| AnemiaBlood and lymphatic system disorders | 2/53 |
| Acute Mental Status ChangeNervous system disorders | 1/53 |
| AppendicitisInfections and infestations | 1/53 |
| Atrial FibrillationCardiac disorders | 1/53 |
| Clostridium DifficileInfections and infestations | 1/53 |
| Event | Carfilzomib, Lenalidomide w/Dexamethasone |
|---|---|
| HyperglycemiaMetabolism and nutrition disorders | 38/53 |
| ThrombocytopeniaBlood and lymphatic system disorders | 36/53 |
| AnemiaBlood and lymphatic system disorders | 32/53 |
| EdemaGeneral disorders | 25/53 |
| HypophosphatemiaMetabolism and nutrition disorders | 24/53 |
| FatigueGeneral disorders | 20/53 |
| Muscle CrampingMusculoskeletal and connective tissue disorders | 17/53 |
| NeutropeniaBlood and lymphatic system disorders | 16/53 |
| RashSkin and subcutaneous tissue disorders | 15/53 |
| Elevated Liver Function TestInvestigations | 15/53 |
| Age, Continuous(years) | Carfilzomib, Lenalidomide w/Dexamethasone |
|---|---|
| Median | 59 (35 to 81) |
| Gender(Participants) | Carfilzomib, Lenalidomide w/Dexamethasone |
|---|---|
| Female | 14 |
| Male | 39 |
This study is completed, as verified in Dec 2016. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Carfilzomib · Lenalidomide · Dexamethasone
University of Michigan Rogel Cancer Center →