Elotuzumab, Pomalidomide, & Dexamethasone (Elo-Pom-Dex) With Second Autologous Stem Cell Transplantation for Relapsed Multiple Myeloma

Study Overview
=================
Brief Summary
-----------------
Based on the need to improve outcomes post second autologous stem cell transplant (ASCT) for multiple myeloma (MM) and the benefits seen of maintenance treatment following initial ASCT, the natural next step is to evaluate maintenance/continuation therapy following second ASCT. Pomalidomide is active against MM cells refractory to both bortezomib and lenalidomide, making it an ideal choice for continuation therapy following second ASCT. Adding elotuzumab may increase efficacy and also the durability of responses which is essential to improving outcomes following second ASCT.

Official Title
-----------------
A Phase II Study of Elotuzumab, Pomalidomide, & Dexamethasone (Elo-Pom-Dex) With Second Autologous Stem Cell Transplantation for Relapsed Multiple Myeloma

Conditions
-----------------
Multiple Myeloma in Relapse

Intervention / Treatment
-----------------
* Drug: Elotuzumab
* Drug: Pomalidomide
* Drug: Dexamethasone


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed diagnosis of multiple myeloma. Received prior autologous stem cell transplantation as first line therapy for multiple myeloma with subsequent disease relapse/progression. Failed 1 or 2 lines of treatment for multiple myeloma. A line of treatment includes all therapy including induction, transplant, and maintenance administered in a sequence in the absence of relapse/progression. Once relapse/progression occurs and subsequently the anti-myeloma treatment is changed, a new line of treatment has begun. Local radiation or corticosteroids will not be considered treatment for multiple myeloma. Received 2 to 6 cycles of induction therapy per standard of care prior to 2nd autologous stem cell transplantation Received standard of care melphalan conditioning for 2nd autologous stem cell transplantation, is currently Day +80 to +120 following transplant, and is responding to therapy (partial response or better as compared to pre-induction assessment. All US study participants must be registered into the mandatory POMALYST REMS® program and be willing and able to comply with the requirements of the POMALYST REMS® program. For Canadian sites, patients will followed according to the Pomalidomide pregnancy prevention program Females of reproductive potential within the US must agree to adhere to the scheduled pregnancy testing as required in the POMALYST REMS® program. For Canadian sites, patients will followed according to the Pomalidomide pregnancy prevention program At least 18 and no more than 75 years of age at enrollment. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 Normal bone marrow and organ function as defined as ALL of the following: Absolute neutrophil count ≥ 1000/mm^3 Platelets ≥ 75,000/mm^3 (transfusions not permitted within 7 days of screening) Total bilirubin ≤ 2.0 x institutional upper limit of normal (IULN) AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN Creatinine clearance ≥ 15 mL/min Females of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry through Day +100 visit. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Able to understand and willing to sign an Institutional Review Board (IRB) approved written informed consent document. Exclusion Criteria: Refractory to elotuzumab and/or pomalidomide, defined as progressive disease or clinical relapse on therapy or within 60 days following completion of therapy. Prior exposure to elotuzumab and/or pomalidomide is allowed as long as patient is not refractory to these agents. More than one prior transplant prior to study entry with the exception of tandem transplantation. Tandem transplantation is defined as two autologous stem cell transplants that occur within 9 months of one another, and the patient did not have disease progression in the period between the two transplants. Presence of peripheral neuropathy ≥ grade 3 based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v 4.0 History of plasma cell leukemia or MM central nervous system (CNS) involvement. Receiving renal replacement therapy, hemodialysis, or peritoneal dialysis. Diagnosed with another concurrent malignancy requiring treatment. Known HIV or active hepatitis A, B, or C. Antidoby testing not required for screening Known hypersensitivity to pomalidomide, dexamethasone, or any excipients in elotuzumab, formulation, or recombinant protein Receiving any other investigational agents within 14 days prior to enrollment. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia. Pregnant and/or breastfeeding. Females of childbearing potential must have two negative pregnancy tests. The first test should be performed within 10-14 days of study entry, and the second test within 24 hours prior to prescribing pomalidomide.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Elotuzumab + Pomalidomide + Dexamethasone<br>Patients will receive 2-6 cycles of salvage/induction per standard of care. After protocol version 02/13/2020, patients may have already received their induction therapy prior to enrolling in the study. Following induction, patients will undergo standard of care ASCT melphalan conditioning (ASCT). Administration of melphalan and the second ASCT will be done as part of routine care and procedures are not dictated by this protocol. Continuation therapy with Elo-Pom-Dex will begin between Days 80 and 120 following the second ASCT: 10 mg/kg of elotuzumab on Days 1 and 15 for Cycles 1-6 followed by 20 mg/kg on Day 1 for Cycles 7+ 2 mg pomalidomide daily on Days 1-21 of all cycles 40 mg dexamethasone on Days 1 and 15 of all cycles for Cycles 1-6 followed by 40 mg on Day 1 for Cycles 7+ Continuation therapy may continue until relapse or progression. | Drug: Elotuzumab<br>* During continuation therapy, elotuzumab will be administered on a 28-day cycle as follows: on Days 1 and 15 for Cycles 1-6 and on Day 1 for Cycles 7+. For Cycles 1-6 elotuzumab will be administered intravenously at a dose of 10 mg/kg. For Cycles 7+ elotuzumab will be administered at a dose of 20 mg/kg.<br>* Other names: Empliciti;Drug: Pomalidomide<br>* During continuation therapy, pomalidomide will be taken by mouth daily on Days 1-21 of each 28-day cycle at a starting dose of 2 mg. During continuation, pomalidomide may be dose escalated to 4 mg at the discretion of the treating physician if the 2 mg dose is tolerated.<br>* Other names: Pomalyst;Drug: Dexamethasone<br>* During continuation therapy, dexamethasone will be taken by mouth at a starting dose of 40 mg. It will be given on a 28-day cycle as follows: on Days 1 and 15 for Cycles 1-6 and on Day 1 only for Cycles 7+. Sufficient quantity of drug for one cycle of therapy will be prescribed to the patient at a time.<br>* Other names: Decadron;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-free Survival (EFS) Rate | -Event-free survival (EFS) will be defined as time from ASCT to disease progression, relapse, or death, whichever occurs first. Patients who are removed from study therapy prior to any of these events occurring will be censored at the time of initiation of subsequent anti-myeloma treatment. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | -Overall response rate (ORR) will be defined as the proportion of evaluable patients meeting the criteria for partial response (PR), very good partial response (VGPR), complete response (CR), or stringent complete response (sCR). | 1 year | 
| Complete Response Rate (CRR) | Complete response rate (CRR) will be defined as the proportion of evaluable patients meeting the criteria complete (CR) or stringent complete response (sCR) Stringent complete response (sCR) requires all of the following: CR as defined below Normal free light chain ratio (0.26-1.65) Absence of clonal cells in the bone marrow by immunohistochemistry or immunofluorescence Complete response (CR) requires all of the following: Disappearance of monoclonal protein by both protein electrophoresis and immunofixation studies from the blood and urine If serum and urine monoclonal protein are unmeasurable, Normal free light chain ratio (0.26-1.65) <5% plasma cells in the bone marrow Disappearance of soft tissue plasmacytoma Patients who do not meet the definition of CR based solely on residual monoclonal protein on serum electrophoresis and/or immunofixation, but are MRD-negative as described above, will also be considered CR. | 1 year | 
| Progression-free Survival (PFS) | -Progression-free survival (PFS) will be defined as time from ASCT to disease progression or relapse. Any patient who expires or withdraws prior to disease progression or relapse will be censored at last follow-up. Patients who are removed from study therapy prior to progression or relapse will be censored at the time of initiation of subsequent anti-myeloma treatment. | Up to 5 years post completion of treatment | 
| Overall Survival (OS) | -Overall survival (OS) will be defined as time from ASCT to death due to any causes. Patients who are alive at the time of data analyses will be censored on the last known alive date. Patients who are removed from study therapy prior death will be censored at the time of initiation of subsequent anti-myeloma treatment. | Up to 5 years post completion of treatment | 
| Toxicity of Regimen as Measured by Number of Grade 3-5 Adverse Events | -The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting. | Up to 30 days following completion of treatment (estimated to be 106 weeks) |