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

Multiple Myeloma in Relapse Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03030261
• Other study ID #: 201701084
• Secondary ID: CA204-225PO-CL-M
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 22, 2017
• Est. completion date: September 26, 2027

Study information

• Verified date: December 2023
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 25
• Est. completion date: September 26, 2027
• Est. primary completion date: September 29, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Multiple Myeloma in Relapse
• Neoplasms, Plasma Cell

Intervention

Drug:
• Elotuzumab
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.
• Pomalidomide
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.
• Dexamethasone
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.

Locations

Country	Name	City	State
Canada	University Health Network - Princess Margaret Cancer Centre	Toronto	Ontario
United States	Colorado Blood Cancer Institute (Sarah Cannon)	Denver	Colorado
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (3)

Lead Sponsor	Collaborator
Washington University School of Medicine	Bristol-Myers Squibb, Celgene

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)