Elotuzumab, Pomalidomide, Bortezomib, and Dexamethasone in Treating Patients with Relapsed or Refractory Multiple Myeloma

Status: Closed to Accrual

Description

This phase II trial studies the side effects and how well elotuzumab, pomalidomide, bortezomib, and dexamethasone work in treating patients with multiple myeloma that has come back or does not respond to treatment. Immunotherapy with monoclonal antibodies, such as elotuzumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Pomalidomide may enhance or suppress the reaction of the immune system to a stimulus which may help the body destroy cancer cells. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Dexamethasone may act against cancer cells and prevent inflammation in a wide variety of organs. Giving elotuzumab, pomalidomide, bortezomib, and dexamethasone may work better in treating patients with multiple myeloma.

Eligibility Criteria

Inclusion Criteria

  • All laboratory assessments should be performed within 21 days of initiation of protocol therapy unless otherwise specified
  • Participant has given voluntary signed written informed consent before performance of any study-related procedure that is not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to their future medical care
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Measurable disease of multiple myeloma as defined by at least one of the following: * Serum monoclonal protein >= 0.5 g/dL * >= 200 mg of monoclonal protein in the urine on 24 hour electrophoresis * Serum free light chain >= 100 mg/L (10 mg/dL) and abnormal serum free kappa to serum free kappa light chain ratio
  • Previously treated relapsed and refractory multiple myeloma * Patients must have received at least one prior line of therapy * Prior therapy must include at least 2 cycles of lenalidomide and at least 2 cycles of a proteasome inhibitor (either in separate regimens or within the same regimen) * Patients must be refractory and/or relapsed/refractory to lenalidomide or prior lenalidomide * Disease progression on or within 60 days of completion of last therapy
  • Absolute neutrophil count (ANC) >= 1000/uL; granulocyte colony-stimulating factor receptor (G-CSF) is not permitted within 14 days of screening; patients with ANC < 1000/uL can be considered for screening on a case by case basis with additional monitoring, after discussion with the principal investigator (PI)
  • Platelet count >= 50,000/uL; platelet transfusion is not permitted within 7 days of screening
  • Hemoglobin >= 8 g/dL; red blood cell transfusions are permitted to meet eligibility criteria
  • Calculated creatinine clearance of >= 30 mL/min according to Cockcroft-Gault equation
  • Serum bilirubin values < 2 mg/dL
  • Serum aspartate transaminase (alanine aminotransferase [ALT]) and/or aspartate transaminase (aspartate aminotransferase [AST]) values < 3 x the upper limit of normal (ULN) of the institutional laboratory reference range; patients with elevated bilirubin due to Gilbert’s syndrome may be permitted with PI approval
  • Must be able to take acetylsalicylic acid (ASA) daily as prophylactic anticoagulation; patients intolerant to ASA may use low molecular weight heparin or equivalent; warfarin will be allowed provided patient is full anticoagulated, with an international normalized ratio (INR) of 2-3
  • All study participants must be registered into the mandatory pomalidomide (POMALYST) Risk Evaluation and Mitigation Strategy (REMS) program, and be willing and able to comply with the requirements of the POMALYST REMS program
  • Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the POMALYST REMS program
  • Able to swallow capsules whole (pomalidomide capsules cannot be crushed, dissolved or broken)

Exclusion Criteria

  • Prior therapy with elotuzumab
  • Participants who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier; patients may have received dexamethasone within 2 weeks prior to entering study
  • Participants who are receiving any other investigational agents
  • Concomitant high dose corticosteroids except patients may be on chronic steroids (maximum dose 10 mg/day prednisone equivalent) if they are being given for disorders other than myeloma, e.g. adrenal insufficiency, rheumatoid arthritis, etc
  • Pregnant or lactating females
  • Prior history of malignancies, other than multiple myeloma (MM), unless the patient has completed definitive treatment and has been free of the disease for >= 3 years; patients who are free of disease < 3 years may enroll after discussion with the principal investigator; exceptions include the following (i.e. the following are eligible to participate): * Basal or squamous cell carcinoma of the skin * Carcinoma in situ of the cervix * Ductal carcinoma in situ of the breast * Incidental histologic finding of prostate cancer (T1a or T1b) managed with surveillance
  • Another malignancy undergoing active treatment with the exception of non-melanoma skin cancer or in situ cervical cancer
  • Patients with plasma cell leukemia, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, or amyloidosis are excluded from this trial
  • Known human immunodeficiency virus (HIV) infection
  • Known active hepatitis B or active hepatitis C infection; participants who have prior hepatitis C infection but who have received an antiviral treatment and show no detectable viral ribonucleic acid (RNA) for 6 months after completion of treatment are eligible
  • Peripheral neuropathy >= grade 2 despite supportive therapy
  • Hypersensitivity to thalidomide, lenalidomide, pomalidomide, bortezomib, or dexamethasone (such as Stevens-Johnson syndrome); rash to immunomodulatory drug that can be medically managed is allowable
  • Allogeneic stem cell transplant less than 12 months prior to initiation of study treatment and who have not discontinued immunosuppressive treatment for at least four weeks prior to initiation of study treatment and who are currently dependent on such treatment; patients may also not have active graft versus (v.) host disease
  • Patient has a history of significant cardiovascular, neurological, endocrine, gastrointestinal, respiratory, or inflammatory illness that could preclude study participation, pose an undue medical hazard, or interfere with the interpretation of the study results, including, but not limited to, patients with congestive heart failure (New York Heart Association [NYHA] class 3 or 4); unstable angina; cardiac arrhythmia; recent (within the preceding 6 months) myocardial infarction or stroke; hypertension requiring > 2 medications for adequate control; diabetes mellitus with > 2 episodes of ketoacidosis in the preceding 12 months; or chronic obstructive pulmonary disease (COPD) requiring > 2 hospitalizations in the preceding 12 months
  • Patient has any other medical, psychiatric, or social condition that would preclude participation in the study, pose an undue medical hazard, interfere with the conduct of the study, or interfere with interpretation of the study results

Locations & Contacts

See trial information on ClinicalTrials.gov for a list of participating sites.

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To evaluate the objective response rate (partial response or better) of elotuzumab in combination with pomalidomide, bortezomib, and dexamethasone in patients with relapsed and refractory multiple myeloma and who have received at least one prior line of therapy and have had received prior lenalidomide and bortezomib and who are refractory to lenalidomide as last line or prior therapy.

II. To evaluate the safety profile of elotuzumab in combination with pomalidomide, bortezomib, and dexamethasone (elotuzumab-PVD).

SECONDARY OBJECTIVES:

I. To evaluate the progression free survival (PFS) of elotuzumab-PVD.

II. To study clonal evolution, clonal heterogeneity, and correlate with response.

III. Correlate response with tumor genotype and expression profile signature.

OUTLINE:

Patients receive elotuzumab intravenously (IV) over 30-110 minutes on days 1, 8, 15, and 22 of courses 1-2, days 1 and 15 of courses 3-8, and day 1 of subsequent courses and pomalidomide orally (PO) once daily (QD) on days 1-21. Patients also receive bortezomib subcutaneously (SC) on days 1, 8, and 15 of courses 1-8 and days 1 and 15 of subsequent courses and dexamethasone PO or IV on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Dana-Farber Harvard Cancer Center

Principal Investigator
Andrew Jenho Yee

Trial IDs

Primary ID 15-475
Secondary IDs NCI-2016-00943
Clinicaltrials.gov ID NCT02718833