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

NCT03333746 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: OSU-17160NCI-2017-01653P30CA016058
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Overall Survival (OS)

  Up to 3 years

• 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

• Time to Progression (TTP)

  Time from start of treatment until the date he or she has progression or dies, assessed up to 3 years

Other Outcomes (4)

• Immunomonitoring of Lymphocytes Subsets Including Natural Killer (NK) Cell

  Up to 3 years

• Immunomonitoring of Lymphocytes Subsets Including T Cell

  Up to 3 years

• Pharmacokinetics: The Maximum Plasma Concentration (Cmax)

  Screening, days 1 and 14 of each cycle

Study Arms (1)

Treatment (lenalidomide, nivolumab)

EXPERIMENTAL

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; Drug: Lenalidomide; Biological: Nivolumab; Other: Pharmacological Study

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (lenalidomide, nivolumab)

Lenalidomide DRUG

Given PO

Also known as: CC-5013, CC5013, CDC 501, Revlimid

Treatment (lenalidomide, nivolumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Treatment (lenalidomide, nivolumab)

Pharmacological Study OTHER

Correlative studies

Treatment (lenalidomide, nivolumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Yvonne Efebera: lead
• National Cancer Institute (NCI): collaborator
• American Cancer Society, Inc.: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Links

• The Jamesline

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Lenalidomide; Nivolumab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Study was discontinued due to FDA recommendations of the potential toxities of the combination of nivolumab with an immunemodulator(lenalidomide, pomalidomde)

Results Point of Contact

• Title: Dr. Yvonne Efebera
• Organization: The Ohio State University Comprehensive Cancer Center

Yvonne.Efebera@osumc.edu

614-293-7243

Study Officials

• Yvonne Efebera, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 6, 2017
• First Posted: November 7, 2017
• Study Start: March 21, 2018
• Primary Completion: August 13, 2018
• Study Completion: November 16, 2018
• Last Updated: May 30, 2019
• Results First Posted: May 30, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)