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

Phase 2

Terminated

Conditions: Recurrent Plasma Cell Myeloma
Refractory Plasma Cell Myeloma

Interventions: Other: Laboratory Biomarker Analysis
Drug: Lenalidomide
Biological: Nivolumab
Other: Pharmacological Study

Registration Number: NCT03333746

Lead Sponsor: Yvonne Efebera

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 1

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (lenalidomide, nivolumab)	Laboratory Biomarker Analysis	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.
Treatment (lenalidomide, nivolumab)	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.
Treatment (lenalidomide, nivolumab)	Pharmacological Study	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.
Treatment (lenalidomide, nivolumab)	Lenalidomide	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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