Elotuzumab, Pomalidomide, and Dexamethasone in Treating Patients with Relapsed or Refractory Multiple Myeloma Undergoing Second Stem Cell Transplant
This phase II trial studies how well elotuzumab, pomalidomide, and dexamethasone work in treating patients with multiple myeloma that has come back or does not respond to treatment who are undergoing a second stem cell transplant. 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. Drugs used in chemotherapy, such as pomalidomide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving elotuzumab, pomalidomide, and dexamethasone may work better in treating patients with multiple myeloma.
- Histologically confirmed diagnosis of multiple myeloma
- Received prior autologous stem cell transplantation as first line therapy for multiple myeloma with subsequent disease relapse/progression
- Refractory to or intolerant of lenalidomide maintenance following first autologous stem cell transplantation; refractory is defined as disease relapse/progression on therapy or within 60 days of completing therapy; intolerance is defined as the inability to administer >= 10 mg per day due to toxicity
- All United States (US) 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; 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
- Candidate for second autologous stem cell transplantation per local institution’s guidelines with at least 2 x 10^6/kg CD34+ autologous stem cells available for transplantation
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- 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)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [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
- Prior exposure to elotuzumab or pomalidomide
- Received systemic multiple myeloma therapy post-relapse/progression; patients that received 1-2 cycles of salvage therapy, local radiation, and/or corticosteroids post-relapse/progression are eligible if there was no further disease progression following administration
- 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 Common Terminology Criteria for Adverse Events version 4.0 (NCI CTCAE v 4.0)
- History of plasma cell leukemia or multiple myeloma (MM) central nervous system (CNS) involvement
- Receiving renal replacement therapy, hemodialysis, or peritoneal dialysis
- Diagnosed with another concurrent malignancy requiring treatment
- Known human immunodeficiency virus (HIV) or active hepatitis A, B, or C; antibody 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
Locations & Contacts
Trial Objectives and Outline
I. To evaluate the one-year event-free survival (EFS) rate of patients with relapsed/refractory multiple myeloma following second autologous stem cell transplantation (ASCT) with elotuzumab-pomalidomide-dexamethasone (Elo-Pom-Dex) induction and continuation therapy.
I. To evaluate the overall response rate (ORR) of patients with relapsed/refractory multiple myeloma following second ASCT with Elo-Pom-Dex induction and continuation therapy.
II. To evaluate the complete response rate (CRR) of patients with relapsed/refractory multiple myeloma following second ASCT with Elo-Pom-Dex induction and continuation therapy.
III. To evaluate the minimal residual disease negative (MRD-negative) rate of patients with relapsed/refractory multiple myeloma following second ASCT with Elo-Pom-Dex induction and continuation therapy.
IV. To evaluate the event-free survival (EFS) of patients with relapsed/refractory multiple myeloma following second ASCT with Elo-Pom-Dex induction and continuation therapy.
V. To evaluate the progression-free survival (PFS) of patients with relapsed/refractory multiple myeloma following second ASCT with Elo-Pom-Dex induction and continuation therapy.
VI. To evaluate the overall survival (OS) of patients with relapsed/refractory multiple myeloma following second ASCT with Elo-Pom-Dex induction and continuation therapy.
VII. To evaluate the toxicity of second ASCT with Elo-Pom-Dex induction and continuation therapy.
I. To evaluate EloShift Assay for more accurate determination of serum monoclonal protein in myeloma patients receiving elotuzumab.
INDUCTION: Patients receive dexamethasone intravenously (IV) or orally (PO) on days 1, 8, 15, and 22, elotuzumab IV on days 1, 8, 15, and 22 of cycles 1-2, and days 1 and 15 of cycles 3-4, and pomalidomide PO daily on days 1-21. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
TRANSPLANT: Patients undergo standard of care second ASCT.
CONTINUATION: Within days 80 and 120 post-ASCT, patients receive dexamethasone IV or PO and elotuzumab IV on days 1 and 15 of cycles 1-6, and day 1 of subsequent cycles. Patients also receive pomalidomide PO daily on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up annually for up to 5 years.
Trial Phase & Type
Siteman Cancer Center at Washington University
Secondary IDs NCI-2017-00101
Clinicaltrials.gov ID NCT03030261