Multiple Myeloma
Conditions
Keywords
lenalidomide maintenance, hematopoietic cell transplantation, serologic relapse
Brief summary
The purpose of this study is determine Time-to-Progression with elotuzumab plus lenalidomide when elotuzumab is added to multiple myeloma participants with serologic relapse/progression while receiving lenalidomide maintenance for each study arm.
Detailed description
This is a randomized parallel 2-cohort phase 2 study of elotuzumab given at 10 mg/kg weekly during induction in combination with lenalidomide (either 25 mg or 10 mg) in patients with multiple myeloma who progress or relapse serologically while on single agent lenalidomide maintenance. The combination therapy with elotuzumab and lenalidomide will be continued until further progression of myeloma (based on response criteria) or intolerability.
Interventions
DRUGElotuzumab
Elotuzumab according to dosing schedule outlined in treatment arms.
DRUGLenalidomide
Lenalidomide according to dosing schedule outlined in treatment arms.
DRUGDexamethasone
Dexamethasone is a commercially available drug. The description, how supplied, and storage instructions for dexamethasone product are found in the prescribing information. During the study, dexamethasone will be administered as premedication for elotuzumab as indicated in the package insert.
Sponsors
Bristol-Myers Squibb
H. Lee Moffitt Cancer Center and Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with multiple myeloma who demonstrate evidence of serologic relapse/progression while on lenalidomide maintenance given as part of first line therapy (including upfront high-dose chemotherapy followed by autologous hematopoietic cell transplantation (HCT)) without symptomatic relapse/progression. Lenalidomide maintenance is defined as single agent lenalidomide therapy of any doses up to 10 mg PO daily for up to 28 days (28-day cycle). * Male or female patients aged ≥ 18 years old * Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed * Measurable disease as outlined in protocol guidelines * Participants must meet laboratory criteria as outlined in protocol guidelines
Exclusion criteria
* Prior Elotuzumab * Patients with clinical relapse/progression as per the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma defined as one or more of the following criteria: * Development of new soft tissue plasmacytomas or bone lesions (osteoporotic fractures do not constitute progression) * Definite increase in the size of existing plasmacytomas or bone lesions. A definite increase is defined as a 50% (and ≥1 cm) increase as measured serially of the measurable lesion * Hypercalcemia (\>11 mg/dL); * Decrease in hemoglobin of ≥2 g/dL not related to therapy or other non-myeloma-related conditions; * Rise in serum creatinine by 2 mg/dL or more from the start of the therapy and attributable to myeloma * Hyperviscosity related to serum paraprotein * Women who are pregnant or breast feeding or women of childbearing potential (WOCBP) not using an effective method of birth control. Women of childbearing potential must have a negative serum pregnancy testing within 7 days prior to the administration of drug. * Male patients whose sexual partners are WOCBP not using effective birth control * Patients with a prior malignancy with in the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix) * Patients with known positivity for human immunodeficiency virus (HIV)) or hepatitis C; baseline testing for HIV and hepatitis C is not required * Patients with a diagnosis of POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or plasma cell leukemia (\> 2.0 × 10\^9/L circulating plasma cells by standard differential)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Progression Free Survival (PFS) | An average of 8 months | Progression free survival (PFS) is defined as the time of randomization to date of death from any cause, date of relapse/progression, or the last follow-up date, whichever comes first. The Kaplan-Meier method will be used to estimate PFS for each Study Arm. The method of Brookmeyer and Crowley will be used to construct 95% confidence interval. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response | Up to 60 days post last study treatment | Overall response with elotuzumab and lenalidomide for each study arm. Overall Response is defined as best Overall Response, as Complete Response or Partial Response. Response will be assessed per the uniform response criteria of the International Myeloma Working Group(IMWG). Myeloma participants enrolled in this clinical study will be assessed for disease response after every cycle. Complete Response= Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<5% plasma cells in bone marrow aspirates; Partial Response= ≥50% reduction of serum M-protein plus reduction in 24 h urinary M-protein by ≥90% or to \<200 mg per 24 h; |
| Minimum Response (MR) | Up to 60 days post last study treatment | Minimum response (MR) or better with elotuzumab and lenalidomide for each study arm. The Consensus on Uniform Reporting of Response will be used to evaluate response. Myeloma participants enrolled in this clinical study will be assessed for disease response after every cycle. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| A: Elotuzumab + Lenalidomide at 25 mg Elotuzumab 10 mg/kg intravenously (IV) weekly (days 1, 8, 15 and 22) for 2 cycles, then 20 mg/kg every 4 weeks. Dexamethasone will be administered as premedication for elotuzumab.
Lenalidomide 25 mg by mouth (PO) daily days 1-21 out of a 28-day schedule.
Elotuzumab: Elotuzumab according to dosing schedule outlined in treatment arms.
Lenalidomide: Lenalidomide according to dosing schedule outlined in treatment arms.
Dexamethasone: Dexamethasone is a commercially available drug. The description, how supplied, and storage instructions for dexamethasone product are found in the prescribing information.
During the study, dexamethasone will be administered as premedication for elotuzumab as indicated in the package insert. | 9 |
| B: Elotuzumab + Lenalidomide at 10 mg Elotuzumab 10 mg/kg IV weekly (days 1, 8, 15 and 22) for 2 cycles, then 20 mg/kg every 4 weeks. Dexamethasone will be administered as premedication for elotuzumab.
Lenalidomide 10 mg PO daily days 1-21 out of a 28-day schedule.
Elotuzumab: Elotuzumab according to dosing schedule outlined in treatment arms.
Lenalidomide: Lenalidomide according to dosing schedule outlined in treatment arms.
Dexamethasone: Dexamethasone is a commercially available drug. The description, how supplied, and storage instructions for dexamethasone product are found in the prescribing information.
During the study, dexamethasone will be administered as premedication for elotuzumab as indicated in the package insert. | 9 |
| Total | 18 |
Baseline characteristics
| Characteristic | A: Elotuzumab + Lenalidomide at 25 mg | B: Elotuzumab + Lenalidomide at 10 mg | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 5 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 4 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 9 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 7 Participants | 13 Participants |
| Region of Enrollment United States | 9 participants | 9 participants | 18 participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 9 |
| other Total, other adverse events | 2 / 9 | 1 / 9 |
| serious Total, serious adverse events | 3 / 9 | 0 / 9 |
Outcome results
Primary
Percentage of Participants With Progression Free Survival (PFS)
Progression free survival (PFS) is defined as the time of randomization to date of death from any cause, date of relapse/progression, or the last follow-up date, whichever comes first. The Kaplan-Meier method will be used to estimate PFS for each Study Arm. The method of Brookmeyer and Crowley will be used to construct 95% confidence interval.
Time frame: An average of 8 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A: Elotuzumab + Lenalidomide at 25 mg | Percentage of Participants With Progression Free Survival (PFS) | 11.1 percentage of participants |
| B: Elotuzumab + Lenalidomide at 10 mg | Percentage of Participants With Progression Free Survival (PFS) | 22.2 percentage of participants |
Secondary
Minimum Response (MR)
Minimum response (MR) or better with elotuzumab and lenalidomide for each study arm. The Consensus on Uniform Reporting of Response will be used to evaluate response. Myeloma participants enrolled in this clinical study will be assessed for disease response after every cycle.
Time frame: Up to 60 days post last study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| A: Elotuzumab + Lenalidomide at 25 mg | Minimum Response (MR) | 2 Participants |
| B: Elotuzumab + Lenalidomide at 10 mg | Minimum Response (MR) | 3 Participants |
Secondary
Overall Response
Overall response with elotuzumab and lenalidomide for each study arm. Overall Response is defined as best Overall Response, as Complete Response or Partial Response. Response will be assessed per the uniform response criteria of the International Myeloma Working Group(IMWG). Myeloma participants enrolled in this clinical study will be assessed for disease response after every cycle. Complete Response= Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<5% plasma cells in bone marrow aspirates; Partial Response= ≥50% reduction of serum M-protein plus reduction in 24 h urinary M-protein by ≥90% or to \<200 mg per 24 h;
Time frame: Up to 60 days post last study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| A: Elotuzumab + Lenalidomide at 25 mg | Overall Response | 1 Participants |
| B: Elotuzumab + Lenalidomide at 10 mg | Overall Response | 2 Participants |