Steroid Sparing Treatment With in Newly Diagnosed Transplant Ineligible Patients With Multiple Myeloma

Study Overview
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Brief Summary
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The purpose of this study is to determine the effects of daratumumab and lenalidomide without steroids for treating patients with multiple myeloma.

Detailed Description
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This is an open label, phase 2 study consisting of daratumumab, lenalidomide and dexamethasone, given upfront in newly diagnosed, transplant ineligible patients with myeloma. Patients participating in the study will be recruited from the Wilmot Cancer Institute, University of Rochester in Rochester, New York and all University of Rochester community affiliates. Patients will be treated with 1800 milligrams of Daratumumab subcutaneously or 16 milligrams/kilograms daratumumab intravenously (IV) weekly for 8 treatments, followed by every 2 weeks for 8 treatments, followed by every 4 weeks. Patients will be treated with 25 milligrams of Lenalidomide days 1-21 out of a 28 day cycle (dose adjustments for creatinine clearance) and 20 milligrams of Dexamethasone at least 60 minutes prior to first infusion of daratumumab. Each cycle consists of 28 days (4 weeks). Response assessments by International Myeloma Working Group criteria for myeloma will be performed every 4 weeks while on therapy.

Official Title
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A Phase II Study of Steroid Sparing Treatment With Daratumumab and Lenalidomide in Newly Diagnosed Transplant Ineligible Patients With Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Daratumumab
* Drug: Lenalidomide
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of multiple myeloma with diagnosis Must not have received previous therapy for multiple myeloma Newly diagnosed and not considered candidate for high-dose chemotherapy Adequate organ system function A performance status ≤ 3 Ability to swallow and retain oral medication Female subjects of child bearing potential must be surgically sterile, be post-menopausal Exclusion Criteria: A diagnosis of primary amyloidosis; monoclonal gammopathy of undetermined significance, smoldering multiple myeloma; non-secretory myeloma A diagnosis of Waldenström's disease Receiving cancer therapy Radiation therapy within 14 days of enrollment Major surgery within 2 weeks before enrollment Human immunodeficiency virus -infected patients must be on effective anti-retroviral therapy with undetectable viral load within the past 6 months Seropositive for hepatitis B, or seropositive for hepatitis C Ongoing systemic bacterial, fungal or viral infection Severe and/or uncontrolled medical conditions Malignancy within 2 years of study enrollment Women who are pregnant or lactating Contraindications to required prophylaxis for deep vein thrombosis and pulmonary embolism.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Experimental Arm: Cycle 1-4 All subjects<br>Subjects will be treated with the following: Daratumumab 16 milligrams/kilograms intravenously weekly for 8 treatments, followed by every 2 weeks for 8 treatments, followed by every 4 weeks Lenalidomide 25 milligrams by mouth daily days 1-21 out of a 28 day cycle Dexamethasone 20 milligrams by mouth or intravenously at least 60 minutes prior to first infusion of daratumumab | Drug: Daratumumab<br>* Daratumumab 16 milligrams/kilograms intravenously weekly for 8 treatments, followed by every 2 weeks for 8 treatments, followed by every 4 weeks<br>* Other names: Darzalex;Drug: Lenalidomide<br>* Lenalidomide 25 milligrams by mouth daily days 1-21 out of a 28 day cycle<br>* Other names: Revlimid;Drug: Dexamethasone<br>* Dexamethasone 20 milligrams by mouth or intravenously at least 60 minutes prior to first infusion of daratumumab<br>* Other names: Ozurdex;|
| Experimental: Experimental Arm: Cycle 5+ Partial Response or Better<br>Subjects will be treated the following: Daratumumab 16 milligrams/kilograms intravenously weekly for 8 treatments, followed by every 2 weeks for 8 treatments, followed by every 4 weeks Lenalidomide 25 milligrams/kilograms daily days 1-21 out of a 28 day cycle | Drug: Daratumumab<br>* Daratumumab 16 milligrams/kilograms intravenously weekly for 8 treatments, followed by every 2 weeks for 8 treatments, followed by every 4 weeks<br>* Other names: Darzalex;Drug: Lenalidomide<br>* Lenalidomide 25 milligrams by mouth daily days 1-21 out of a 28 day cycle<br>* Other names: Revlimid;|
| Active Comparator: Experimental Arm: Cycle 5+ Less than Partial Response<br>Subjects will be treated the following: Daratumumab 16 milligrams/kilograms intravenously weekly for 8 treatments, followed by every 2 weeks for 8 treatments, followed by every 4 weeks Lenalidomide 25 milligrams by mouth daily days 1-21 out of a 28 day cycle Dexamethasone 20 milligrams by mouth or intravenously at least 60 minutes prior to first infusion of daratumumab | Drug: Daratumumab<br>* Daratumumab 16 milligrams/kilograms intravenously weekly for 8 treatments, followed by every 2 weeks for 8 treatments, followed by every 4 weeks<br>* Other names: Darzalex;Drug: Lenalidomide<br>* Lenalidomide 25 milligrams by mouth daily days 1-21 out of a 28 day cycle<br>* Other names: Revlimid;Drug: Dexamethasone<br>* Dexamethasone 20 milligrams by mouth or intravenously at least 60 minutes prior to first infusion of daratumumab<br>* Other names: Ozurdex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daratumumab Related Infusion Reactions | To determine the rate of daratumumab related infusion reactions in patients treated for myeloma without steroids compared to historical controls. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of Response Rates | To determine the proportion of patients who do not achieve at least a partial response after 4 cycles and require steroids to be added back to their regimen | 28 days |