Lenalidomide and Nivolumab in Treating Patients With Relapsed or Refractory Multiple Myeloma

Phase II Study of Lenalidomide in Combination With Nivolumab In Patients With Relapsed/Refractory Multiple Myeloma

This phase II trial studies how well lenalidomide and nivolumab work in treating patients with multiple myeloma that has come back or does not respond to treatment. Drugs used in chemotherapy, such as lenalidomide, 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. Monoclonal antibodies, such as nivolumab, may interfere with the ability of cancer cells to grow and spread. Giving lenalidomide and nivolumab may work better in treating patients with multiple myeloma.

Study Overview

• Status: Terminated
• Conditions: Refractory Plasma Cell Myeloma; Recurrent Plasma Cell Myeloma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Other: Pharmacological Study; Drug: Lenalidomide

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the efficacy of nivolumab in combination with lenalidomide (Revlimid) in terms of overall response rate in patients with relapse/refractory multiple myeloma (MM).

OUTLINE:

Patients receive lenalidomide orally (PO) on days 1-21 and nivolumab intravenously (IV) over 1 hour on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with evidence of relapse or refractory disease as defined by International Myeloma Working Group (IMWG) criteria and measurable disease as defined by any of the following:

  • Serum m-protein >= 0.5 g/dl (>= 10 g/l)
  • Urine monoclonal protein >= 200 mg/24 hour(h)
  • Involved free light chain (FLC) level >= 10mg/dl (>= 100mg/l) and an abnormal serum free light chain ratio (< 0.26, or > 1.65)
  • Measurable biopsy proven plasmacytoma (should be measured within 28 days of initial investigational agent dosing)
• Patients must have had at least 2 prior line of therapy
• Patients must not have had progression of disease on lenalidomide 25 mg; stable disease on lenalidomide is permitted
• Patient may be enrolled at any time from last line of therapy
• Patients must have absolute neutrophil count (ANC) > 1000/uL
• Platelets >= 75,000/uL, if plasma cell percentage on bone marrow biopsy aspirate or core is > 30%, platelet eligibility requirement will be adjusted to 60,000/ul
• Total bilirubin =< 1.5 mg/dL
• Alkaline phosphatase =< 3 X the upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2 X the ULN
• Patients must have adequate renal function as evidenced by serum creatinine =< 2 mg/dL or calculated creatinine clearance of >= 40 ml/min within 14 days of registration using Modification of Diet in Renal Disease (MDRD) formula
• Patient must be able to swallow capsule or tablet
• Patients must provide informed consent
• Patients must have a left ventricular ejection fraction > 30%, no uncontrolled arrhythmias or New York Heart Association class III-IV heart failure
• Patients must have a Karnofsky performance status >= 70
• A negative pregnancy test will be required for all women of child bearing potential; breast feeding is not permitted

• Fertility requirements

  • Female patients with child bearing potential must have a negative pregnancy test at least 7 days before starting treatment drugs
  • Male patients must agree to use an adequate method of contraception for the duration of the study and for 7 months afterwards
  • Female patients must be either posy-menopausal, free from menses >= 2 years (yrs), surgically sterilized, willing to use two adequate barrier methods of contraception to prevent pregnancy, or agree to abstain from sexual activity starting from screening and for 5 months afterwards
  • Female patients of child bearing potential must agree to comply with the fertility and pregnancy test requirements dictated by the Rev-Assist program

Exclusion Criteria:

• Patients with peripheral neuropathy > Common Terminology Criteria for Adverse Events (CTCAE) grade 2
• Patients receiving concurrent corticosteroids at the time protocol therapy is initiated other than for physiologic maintenance treatment
• History of allergic reaction (including erythema nodosum) to lenalidomide
• Concurrent use of complementary or alternative medicines that would confound the interpretation of toxicities and antitumor activity of the study drugs
• Patients with contraindication to thromboprophylaxis
• Unacceptable cardiac risk factors defined by any of the following criteria: patients with congenital long QT syndrome, any history of ventricular fibrillation or torsade de pointes, bradycardia defined as heart rate (HR) < 50 bpm, left ventricular ejection fraction < 30%
• Patients who have received targeted or investigational agents within 2 weeks or within 5 half-lives of the agent and active metabolites (whichever is longer) and who have not recovered from side effects of those therapies
• Patients who have undergone major surgery =< 2 weeks prior to starting study drug or who have not recovered from the side-effects of surgery
• Patients with known positivity for human immunodeficiency virus (HIV), or hepatitis C; baseline testing for HIV and hepatitis C is not required
• Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention, other than non-melanoma skin cancer and carcinoma in situ of the cervix should not be enrolled; patients are not considered to have a ?currently active? malignancy if they have completed therapy for a prior malignancy, are disease free from a prior malignancy for >= 5 yrs and are considered by their physician to be less than 30% risk of relapse
• Patients with active (untreated or relapsed) central nervous system (CNS) metastasis of the patient?s myeloma
• Patients with a history of gastrointestinal surgery or other procedure that might, in the opinion of the investigator(s), interfere with the absorption or swallowing of the study drugs
• Patients with any significant history of non-compliance to medical regimens or unwilling or unable to comply with the instructions given to them by the study staff
• Any other medical condition, including mental illness or substance abuse, deemed by the investigator(s) to likely interfere with the patient?s ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment (lenalidomide, nivolumab); Patients receive lenalidomide PO on days 1-21 and nivolumab IV over 1 hour on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis; Correlative studies; Biological: Nivolumab; Given IV; Other Names: BMS-936558; MDX-1106; NIVO; ONO-4538; Opdivo; Other: Pharmacological Study; Correlative studies; Drug: Lenalidomide; Given PO; Other Names: CC-5013; Revlimid; CC5013; CDC 501

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR (Overall Response Rate)	Will be assessed by IMWG response criteria. 95% binomial confidence intervals will also be calculated for the estimate of the proportion of responses.	Up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Will evaluate other clinical outcomes using the methods of Kaplan-Meier.	Up to 3 years
Progression Free Survival (PFS)	Will evaluate other clinical outcomes using the methods of Kaplan-Meier.	Time from study entry until disease progression or death at trial closure for the per protocol population, assessed up to 3 years
Time to Progression (TTP)	Will be assessed.	Time from start of treatment until the date he or she has progression or dies, assessed up to 3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunomonitoring of Lymphocytes Subsets Including Natural Killer (NK) Cell	Will be explored using graphical analyses as well as summarized quantitatively.	Up to 3 years
Immunomonitoring of Lymphocytes Subsets Including T Cell	Will be explored using graphical analyses as well as summarized quantitatively.	Up to 3 years
Pharmacokinetics: The Maximum Plasma Concentration (Cmax)	Will be assessed using Cmax for Nivolumab in combination with lenalidomide	Screening, days 1 and 14 of each cycle
Pharmacodynamics Profiles:Time to Maximum Plasma Concentration (Tmax)	Will be assessed using Tmax for Nivolumab in combination with lenalidomide	Screening, days 1 and 14 of each cycle

Collaborators and Investigators

• Sponsor: Yvonne Efebera
• Collaborators: Bristol-Myers Squibb; National Cancer Institute (NCI); American Cancer Society, Inc.

Publications and helpful links

Helpful Links

• The Jamesline

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 21, 2018
• Primary Completion (ACTUAL): August 13, 2018
• Study Completion (ACTUAL): November 16, 2018

Study Registration Dates

• First Submitted: October 6, 2017
• First Submitted That Met QC Criteria: November 2, 2017
• First Posted (ACTUAL): November 7, 2017

Study Record Updates

• Last Update Posted (ACTUAL): May 30, 2019
• Last Update Submitted That Met QC Criteria: May 29, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Immune Checkpoint Inhibitors; Lenalidomide; Nivolumab
• Other Study ID Numbers: OSU-17160; P30CA016058 (U.S. NIH Grant/Contract); NCI-2017-01653 (REGISTRY: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No