Elotuzumab Plus Lenalidomide (Elo/Rev) for Serologic Relapse/Progression While on Lenalidomide
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: 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. |
Drug: Elotuzumab
Elotuzumab according to dosing schedule outlined in treatment arms.
Other Names:
Drug: Lenalidomide
Lenalidomide according to dosing schedule outlined in treatment arms.
Other Names:
Drug: 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.
Other Names:
|
| Active Comparator: 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. |
Drug: Elotuzumab
Elotuzumab according to dosing schedule outlined in treatment arms.
Other Names:
Drug: Lenalidomide
Lenalidomide according to dosing schedule outlined in treatment arms.
Other Names:
Drug: 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.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- Overall Response Rate (ORR) [Up to 60 days post last study treatment]
Overall response rate (ORR) 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.
- Minimum Response (MR) [Up to 60 days post last study treatment]
Minimum response (MR) or better rate 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 to Next Treatment (TTNT) [Up to 60 days post last study treatment]
Time to next treatment (TTNT): Median time free of treatment per study arm.
Eligibility Criteria
Criteria
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)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | H. Lee Moffitt Cancer Center and Research Institute | Tampa | Florida | United States | 33612 |
Sponsors and Collaborators
- H. Lee Moffitt Cancer Center and Research Institute
- Bristol-Myers Squibb
Investigators
- Principal Investigator: Melissa Alsina, M.D., H. Lee Moffitt Cancer Center and Research Institute
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.- MCC-19197
- NCI-2018-00891
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | A: Elotuzumab + Lenalidomide at 25 mg | B: Elotuzumab + Lenalidomide at 10 mg |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Period Title: Overall Study | ||
| STARTED | 9 | 9 |
| COMPLETED | 9 | 9 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | A: Elotuzumab + Lenalidomide at 25 mg | B: Elotuzumab + Lenalidomide at 10 mg | Total |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | Total of all reporting groups |
| Overall Participants | 9 | 9 | 18 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
7
77.8%
|
4
44.4%
|
11
61.1%
|
| >=65 years |
2
22.2%
|
5
55.6%
|
7
38.9%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
3
33.3%
|
4
44.4%
|
7
38.9%
|
| Male |
6
66.7%
|
5
55.6%
|
11
61.1%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
| Not Hispanic or Latino |
9
100%
|
9
100%
|
18
100%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
1
11.1%
|
1
5.6%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
3
33.3%
|
1
11.1%
|
4
22.2%
|
| White |
6
66.7%
|
7
77.8%
|
13
72.2%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
9
100%
|
9
100%
|
18
100%
|
Outcome Measures
| Title | Percentage of Participants With Progression Free Survival (PFS) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | A: Elotuzumab + Lenalidomide at 25 mg | B: Elotuzumab + Lenalidomide at 10 mg |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 9 | 9 |
| Number (95% Confidence Interval) [percentage of participants] |
11.1
123.3%
|
22.2
246.7%
|
| Title | Overall Response Rate (ORR) |
|---|---|
| Description | Overall response rate (ORR) 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Minimum Response (MR) |
|---|---|
| Description | Minimum response (MR) or better rate 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Time to Next Treatment (TTNT) |
|---|---|
| Description | Time to next treatment (TTNT): Median time free of treatment per study arm. |
| Time Frame | Up to 60 days post last study treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
Adverse Events
| Time Frame | Adverse events were collected from cycle 1, day 1, and only while the participants were on study treatment only for up to a total of 12 months. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | A: Elotuzumab + Lenalidomide at 25 mg | B: Elotuzumab + Lenalidomide at 10 mg | ||
| Arm/Group Description | 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. | 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. | ||
All Cause Mortality |
||||
| A: Elotuzumab + Lenalidomide at 25 mg | B: Elotuzumab + Lenalidomide at 10 mg | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/9 (0%) | 0/9 (0%) | ||
Serious Adverse Events |
||||
| A: Elotuzumab + Lenalidomide at 25 mg | B: Elotuzumab + Lenalidomide at 10 mg | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/9 (33.3%) | 0/9 (0%) | ||
| Cardiac disorders | ||||
| Non-cardiac chest pain | 1/9 (11.1%) | 1 | 0/9 (0%) | 0 |
| General disorders | ||||
| Fever | 1/9 (11.1%) | 1 | 0/9 (0%) | 0 |
| Infections and infestations | ||||
| Lung Infection - Probable Pneumonia | 1/9 (11.1%) | 1 | 0/9 (0%) | 0 |
| Lung Infection | 1/9 (11.1%) | 1 | 0/9 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| A: Elotuzumab + Lenalidomide at 25 mg | B: Elotuzumab + Lenalidomide at 10 mg | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/9 (22.2%) | 1/9 (11.1%) | ||
| General disorders | ||||
| Fatigue | 1/9 (11.1%) | 2 | 0/9 (0%) | 0 |
| Investigations | ||||
| Neutrophil count decreased | 0/9 (0%) | 0 | 1/9 (11.1%) | 1 |
| Nervous system disorders | ||||
| Syncope | 1/9 (11.1%) | 1 | 0/9 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Melissa Alsina |
|---|---|
| Organization | Moffitt Cancer Center |
| Phone | 813-745-7202 |
| Melissa.Alsina@moffitt.org |
- MCC-19197
- NCI-2018-00891