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

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ClinicalTrials.gov Identifier: NCT03333746
Recruitment Status : Recruiting
First Posted : November 7, 2017
Last Update Posted : July 18, 2018
Sponsor:
Collaborators:
National Cancer Institute (NCI)
American Cancer Society, Inc.
Bristol-Myers Squibb
Information provided by (Responsible Party):
Yvonne Efebera, Ohio State University Comprehensive Cancer Center

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.

Condition or disease Intervention/treatment Phase
Recurrent Plasma Cell Myeloma Refractory Plasma Cell Myeloma Other: Laboratory Biomarker Analysis Drug: Lenalidomide Biological: Nivolumab Other: Pharmacological Study Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Lenalidomide in Combination With Nivolumab In Patients With Relapsed/Refractory Multiple Myeloma
Actual Study Start Date : March 21, 2018
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

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

Drug: Lenalidomide
Given PO
Other Names:
  • CC-5013
  • CC5013
  • CDC 501
  • Revlimid

Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo

Other: Pharmacological Study
Correlative studies




Primary Outcome Measures :
  1. ORR (Overall Response Rate) [ Time Frame: 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 :
  1. Overall survival (OS) [ Time Frame: Up to 3 years ]
    Will evaluate other clinical outcomes using the methods of Kaplan-Meier.

  2. Progression free survival (PFS) [ Time Frame: 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.

  3. Time to progression (TTP) [ Time Frame: Time from start of treatment until the date he or she has progression or dies, assessed up to 3 years ]
    Will be assessed.


Other Outcome Measures:
  1. Immunomonitoring of lymphocytes subsets including natural killer (NK) cell [ Time Frame: Up to 3 years ]
    Will be explored using graphical analyses as well as summarized quantitatively.

  2. Immunomonitoring of lymphocytes subsets including T cell [ Time Frame: Up to 3 years ]
    Will be explored using graphical analyses as well as summarized quantitatively.

  3. Pharmacokinetics: The Maximum Plasma Concentration (Cmax) [ Time Frame: Screening, days 1 and 14 of each cycle ]
    Will be assessed using Cmax for Nivolumab in combination with lenalidomide

  4. Pharmacodynamics Profiles:Time to Maximum Plasma Concentration (Tmax) [ Time Frame: Screening, days 1 and 14 of each cycle ]
    Will be assessed using Tmax for Nivolumab in combination with lenalidomide



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03333746


Contacts
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Contact: The Ohio State University Comprehensive Cancer Center 800-293-5066 OSUCCCClinicaltrials@osumc.edu
Contact: Cassidy Clark 614-688-8821 Cassidy.Clark@osumc.edu

Locations
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United States, Ohio
Ohio State University Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Yvonne A. Efebera, MD    614-293-2268    yvonne.efebera@osumc.edu   
Contact: Misty Fleming    614-688-9498    misty.fleming@osumc.edu   
Principal Investigator: Yvonne A. Efebera, MD         
Sponsors and Collaborators
Yvonne Efebera
National Cancer Institute (NCI)
American Cancer Society, Inc.
Bristol-Myers Squibb
Investigators
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Principal Investigator: Yvonne Efebera, MD Ohio State University Comprehensive Cancer Center

Additional Information:
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Responsible Party: Yvonne Efebera, Principal Investigator, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT03333746     History of Changes
Other Study ID Numbers: OSU-17160
NCI-2017-01653 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
P30CA016058 ( U.S. NIH Grant/Contract )
First Posted: November 7, 2017    Key Record Dates
Last Update Posted: July 18, 2018
Last Verified: July 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Nivolumab
Lenalidomide
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors