2017-03: A Single-Arm, Open-label Study of Anti-Signaling Lymphocytic Activation Molecule F7 (Anti-SLAMF7) Monoclonal Antibody (mAb) Therapy After Autologous Stem Cell Transplant in Patients With Multiple Myeloma

Study Overview
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Brief Summary
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The Total Therapy treatment regimens developed at the Myeloma Institute have demonstrated great improvement in treatment outcomes for multiple myeloma patients. However, some patients still relapse early during maintenance treatment meaning that better options are still needed. This study will evaluate a treatment regimen that alternates two different 3-drug regimens every eight weeks for patients that have previously completed autologous stem cell transplant. The two regimens are bortezomib, lenalidomide, and dexamethasone (VRD) which will be alternated with Elotuzumab, lenalidomide, and dexamethasone (Elo RD). Effectiveness will be measured by the depth of response (i.e., whether or not minimal residual disease (MRD) negative status is achieved). The rate of MRD negativity from this study will be compared to historical control data from the Total Therapy 4 trial which used continuous VRD maintenance therapy after stem cell transplant(s).

Official Title
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University of Arkansas (UARK# 2017-03): A Single-Arm, Open-label Study of Anti-SLAMF7 mAb Therapy After Autologous Stem Cell Transplant in Patients With Multiple Myeloma (Total Therapy 8)

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Elotuzumab
* Drug: Lenalidomide
* Drug: Dexamethasone
* Drug: Bortezomib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must be at least 18 years of age and not older than 75 years of age at the time of enrollment. Patients must have completed a stem cell transplant regimen for newly diagnosed multiple myeloma (MM) consisting of (at least) induction chemotherapy and single or tandem autologous stem cell transplant (ASCT) within eight months of study enrollment. The completed regimen may have included post-transplant consolidation therapy, but post-transplant consolidation is not required. Patients must have achieved at least a partial response (PR) (according to International Myeloma Working Group (IMWG) criteria) in response to the completed transplant regimen. ECOG ≤ 2 (ECOG of 3 allowed if solely due to symptoms of MM-related bone disease). Patients must have absolute neutrophil count (ANC) ≥ 1,000/mm3 and a platelet count of ≥ 75,000/μL. Patients must have a baseline serum creatinine level of < 3 mg/dL and baseline alanine aminotransferase (ALT) < 3x Upper limit of normal (ULN) Toxicities related to prior therapies must be resolved to ≤ Grade 2 according to NCI Common Terminology for Adverse Events (CTCAE) Version 4. Female patients must be: Postmenopausal for at least 1 year before the screening visit, OR Surgically sterile, OR If they are of childbearing potential, agree to practice 2 simultaneous effective methods of contraception, from the time of signing the informed consent form through 90 days after the last dose of study drug, OR Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.) Male patients, even if surgically sterilized (ie, post-vasectomy) must agree to one of the following: Practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR Practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.) Patients must sign an Institutional Review Board (IRB)-approved informed consent indicating their understanding of the proposed treatment and understanding that the protocol has been approved by the IRB. Exclusion Criteria: Female patients who are nursing or pregnant may not participate. Women of childbearing potential must have a negative pregnancy documented within one week of beginning study treatment. Refer to the Revlimid Risk Evaluation and Mitigation Strategies (REMS) program for more information. History of poorly controlled hypertension, diabetes mellitus, active or uncontrolled hepatitis, or other serious medical or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol, or that in the opinion of the investigator would constitute a hazard for participating in this study. History of clinically significant cardiac disease as determined by the enrolling physician including cardiac amyloidosis. Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has not received treatment for one year prior to enrollment. Other cancers will be acceptable if the patient's life expectancy exceeds five years. Known allergies, hypersensitivity, or intolerance to monoclonal antibodies or human proteins or any of the study medications, their analogues, or excipients in the various formulations of any agent (refer to the latest versions of the package inserts).

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Treatment<br>Elotuzumab (10 mg Days 1 and 15), lenalidomide (15 mg Days 1-21), and dexamethasone (20 mg days 1, 8, 15, and 22) administered in 28-day cycles which will be alternated every 8 weeks with bortezomib (1.0 mg Days 1, 8, and 15), lenalidomide (15 mg Days 1-21), and dexamethasone (20 mg Days 1, 8, 15, and 22) | Drug: Elotuzumab<br>* administered via IV infusion<br>* Other names: Empliciti;Drug: Lenalidomide<br>* taken by mouth<br>* Other names: Revlimid;Drug: Dexamethasone<br>* taken by mouth<br>* Other names: Decadron;Drug: Bortezomib<br>* administered as a subcutaneous injection<br>* Other names: Velcade;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Depth of Response | Depth of response will be measured by minimal residual disease (MRD) status (i.e., positive or negative). | Six months from start of study treatment. |