A Study of Durvalumab in Combination With Lenalidomide With and Without Dexamethasone in Adults With Newly Diagnosed Multiple Myeloma

NCT02685826 | Completed Phase 1 Results

• 3 other identifiers: MEDI4736-MM-0022015-004831-11U1111-1179-8722
• Study Type: interventional
• Target: 56
• Locations: 8 countries
• Sites: 54

Brief Summary

This is a multicenter, open-label, Phase 1/2 study to determine the recommended dose and regimen of durvalumab in combination with lenalidomide (LEN) with and without dexamethasone (dex) in adults with newly diagnosed multiple myeloma (NDMM). The study will consist of a dose-finding phase as well as a parallel dose-expansion phase to determine the optimal regimen. \*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\* The study was placed on full clinical hold by the United States (US) Food and Drug Administration (FDA) on 05 Sep 2017. The decision by the FDA was based on data from non-Celgene-sponsored studies related to risks of anti-programmed cell death 1 (PD-1), pembrolizumab, in combination with immunomodulatory agents. As the result, the study was closed for further enrollment, and all subjects were discontinued from all study treatments (durvalumab, lenalidomide and dexamethasone). All subjects are being followed for second primary malignancies (SPMs), every 6 months for 5 years after the last subject has been enrolled as per protocol. After stopping data collection in the clinical database, any SPM events will continue to be recorded in the subject's source documents, and reported to Celgene Drug Safety.

Conditions

Multiple Myeloma

Keywords

Open-label; Phase 1/2; Durvalumab; MEDI4736; Lenalidomide (Len); Dexamethasone (dex); Multiple Myeloma; Newly-Diagnosed (NDMM); Transplant Non-eligible (TNE); PD-L1; Durvalumab (DURVA)

Outcome Measures

Primary Outcomes (1)

• Participants With Dose-Limiting Toxicities (DLTs) During the Dose-Determining Timeframe (Day 1 - Day 28)

  A Dose Review Team (DRT) evaluated DLTs to determine the recommended dose (RD) of Durvalumab to use in the Expansion Period. A DLT was defined as: a. Grade 4 neutropenia for \>= 5 days. b. Grade 3 neutropenia associated with fever (≥ 38.5°C / 101.3°F) of any duration. c. Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding, or platelets transfusion. d. Grade 4 hematologic toxicity that does not resolve to baseline level \<=72 hours. e. Grade 4 anemia, unexplained by underlying disease. f. Any nonhematologic toxicity Grade ≥ 3 except for alopecia and nausea. g. Treatment interruption \>= 2 weeks due to AE. If ≤ 1 of the 6 initial participants in each cohort experience a DLT during cycle 1, the RD was Durvalumab 1500 mg; If \>=2 of the 6 initial participants in any cohort experience a DLT during cycle 1, the maximum tolerated dose (MTD) was exceeded and the dose level of Durvalumab was de-escalated to 750 mg

  First treatment cycle: Day 1 to Day 28

Secondary Outcomes (25)

• Participants With Treatment Emergent Adverse Events (TEAE)

  Day 1 up to Week 84 (the longer of 90 days after discontinuing treatment with DURVA, or 28 days after the last dose of LEN or dex)

• Overall Response Rate (ORR) for Cohorts A and B: Percentage of Participants Who Achieved a Partial Response or Better According to the International Myeloma Working Group (IMWG) Uniform Response Criteria

  Day 1 of each cycle starting with Cycle 2 up to Cycle 17 plus one week for the end of treatment visit (Day 29 up to Week 73)

• Response Improvement Rate (RIR) for Cohort C: Percentage of Participants Achieving a Response Improved From Cycle 1 Day 1 as Assessed by the Investigators Using the International Myeloma Working Group (IMWG) Uniform Response Criteria

  Baseline (Cycle 1 Day 1); Treatment: Day 1 of each cycle starting with Cycle 2 up to Cycle 15 plus one week for the end of treatment visit (Day 29 up to Week 61)

• Time to Response (for Cohorts A and B)

  Day 1 of each cycle starting with Cycle 2 up to Cycle 17 plus one week for the end of treatment visit (Day 29 up to Week 73)

• Kaplan-Meier Estimates for Duration of Response (for Cohort A and B)

  Day 1 of each cycle starting with Cycle 2 up to Cycle 17 plus one week for the end of treatment visit (Day 29 up to Week 73)

Study Arms (3)

Cohort A: High risk, TNE

EXPERIMENTAL

High risk, transplant non-eligible \[TNE\], newly diagnosed multiple myeloma (NDMM) participants who were administered * Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle * Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance \[CrCl\]) value on Days 1 to 21 of each 28-day treatment cycle * Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle

Drug: Durvalumab; Drug: Lenalidomide; Drug: Dexamethasone

Cohort B: >=65 years old, TNE

EXPERIMENTAL

\>= 65 years old, transplant non-eligible \[TNE\], newly diagnosed multiple myeloma (NDMM) participants who were not high risk were administered * Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle * Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance \[CrCl\]) value on Days 1 to 21 of each 28-day treatment cycle * Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle, up to 12 cycles

Drug: Durvalumab; Drug: Lenalidomide; Drug: Dexamethasone

Cohort C: High risk, Post-transplant

EXPERIMENTAL

High risk, post-transplant NDMM participants were administered the following as maintenance therapy: * Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle * Oral lenalidomide (LEN) 10 mg/day on Days 1 to 21 of each 28-day treatment cycle

Drug: Durvalumab; Drug: Lenalidomide

Interventions

Durvalumab DRUG

single use vials administered via intravenous infusion

Also known as: MEDI4736, DUR, DURVA

Cohort A: High risk, TNE; Cohort B: >=65 years old, TNE; Cohort C: High risk, Post-transplant

Lenalidomide DRUG

capsules for oral administration

Also known as: LEN, Revlimid

Cohort A: High risk, TNE; Cohort B: >=65 years old, TNE; Cohort C: High risk, Post-transplant

Dexamethasone DRUG

tablets for oral administration

Also known as: corticosteroid, dex

Cohort A: High risk, TNE; Cohort B: >=65 years old, TNE

Eligibility Criteria

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

You may qualify if:

• Subjects must satisfy the following criteria to be enrolled into the study:
• Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF)
• Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted
• Subject is willing and able to adhere to the study visit schedule and other protocol requirements
• Subject must have documented diagnosis with previously untreated (for cohort C, the induction and consolidation treatment along with the first autologous stem cell transplantation (ASCT) are allowed), symptomatic multiple myeloma (MM) as defined by the criteria below:
• MM diagnostic criteria (all 3 required);
• \- Monoclonal protein present in the serum and/or urine
• Clonal bone marrow plasma cells ≥10% or biopsy-proven bony or extramedullary plasmacytoma
• Any one or more of the following myeloma defining events:
• \. one or more of the following Myeloma-related organ dysfunction (at least one of the following);
• (C) Calcium elevation (serum calcium \>11.5 mg/dl )(\>2.65 mmol/L)
• (R) Renal insufficiency (serum creatinine \>2 mg/dl)(177 µmol/L or more) or creatinine clearance \< 40 ml/min
• (A) Anemia (hemoglobin \<10 g/dL or \>2 g/dL below the lower limit of laboratory normal)
• (B) Bone lesions (lytic or osteopenic) one or more bone lesions on skeletal radiography, computed tomography (CT), or positron emission tomography-computed tomography (PET-CT)
• \. one or more of the following biomarkers of malignancy:

You may not qualify if:

• The presence of any of the following will exclude a subject from enrollment:
• Previous treatment with anti-myeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid (ie, less than or equal to the equivalent of dexamethasone 40 mg/day for 4 days; such a short course of steroid treatment must not have been given within 14 days of Cycle 1 Day 1), for Cohort C, the induction and consolidation treatment along with the first Autologous stem cell transplantation (ASCT) are allowed)
• Any of the following laboratory abnormalities:
• Absolute neutrophil count (ANC) \< 1,000/μL
• Untransfused platelet count \< 75,000 cells/μL
• Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase (SGOT/AST) or alanine aminotransferase (SGPT/ALT) \> 2.5\*upper limit of normal (ULN)
• Serum total bilirubin \> 1.5\*ULN or \> 3.0 mg/dL for subjects with documented Gilbert's syndrome
• Corrected serum calcium \>13.5 mg/dL (\> 3.4 mmol/L)
• Renal failure requiring hemodialysis or peritoneal dialysis
• Any serious medical condition that places the subject at an unacceptable risk if he or she participates in this study. Examples of such a medical condition are, but are not limited to, subject with unstable cardiac disease as defined by: cardiac events such as myocardial infarction (MI) within the past 6 months, NYHA (New York Heart Association) heart failure class III-IV, uncontrolled atrial fibrillation or hypertension; subjects with conditions requiring chronic steroid or immunosuppressive treatment, such as rheumatoid arthritis, multiple sclerosis and lupus, that likely need additional steroid or immunosuppressive treatments in addition to the study treatment
• Peripheral neuropathy ≥ Grade 2
• Primary AL (immunoglobulin light-chain) amyloidosis and myeloma complicated by amyloidosis
• Prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥ 5 years with the exception of the following non-invasive malignancies:
• Basal cell carcinoma of the skin
• Squamous cell carcinoma of the skin

Sponsors & Collaborators

• Celgene: lead

Study Sites (54)

University of Alabama Birmingham

Birmingham, Alabama, 35294-000, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Weill Medical College of Cornell University

New York, New York, 10065, United States

Location

Carolinas Healthcare System

Charleston, South Carolina, 28203, United States

Location

Swedish Medical Center

Seattle, Washington, 98104, United States

Location

Local Institution - 206

Calgary, Alberta, T2N 4N2, Canada

Location

Tom Baker Cancer Center

Calgary, Alberta, T2N 4N2, Canada

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

Local Institution - 203

Edmonton, Alberta, T6G 1Z2, Canada

Location

British Columbia Cancer Agency

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Local Institution - 202

Halifax, Nova Scotia, B3H 2Y9, Canada

Location

Queen Elizabeth II Health Sciences Centre

Halifax, Nova Scotia, B3H 2Y9, Canada

Location

Local Institution - 205

Toronto, Ontario, M5G 2M9, Canada

Location

Princess Margaret Hospital and University of Toronto

Toronto, Ontario, M5G 2M9, Canada

Location

Local Institution - 901

Copenhagen, 2100, Denmark

Location

Rigshospitalet University Hospital

Copenhagen, 2100, Denmark

Location

Local Institution - 903

Odense, 5000, Denmark

Location

Odense Universitetshospital

Odense, 5000, Denmark

Location

Local Institution - 902

Vejle, 7100, Denmark

Location

Vejle Hospital

Vejle, 7100, Denmark

Location

Helsinki UniversityCentral Hospital

Helsinki, 00029 HUS, Finland

Location

Local Institution - 801

Helsinki, 00029 HUS, Finland

Location

Universitatsklinikum Essen

Essen, 45122, Germany

Location

Local Institution - 304

Koblenz, 56068, Germany

Location

Praxis fuer Haematologie und Onkologie Koblenz

Koblenz, 56068, Germany

Location

Local Institution - 302

Tübingen, 72076, Germany

Location

University of Tubingen

Tübingen, 72076, Germany

Location

Local Institution - 404

Rome, Roma, 168, Italy

Location

Local Institution - 405

Bologna, 40138, Italy

Location

Policlinico S. Orsola

Bologna, 40138, Italy

Location

I.R.C.C.S. Policlinico San Matteo - Universita di Pavia

Pavia, 27100, Italy

Location

Local Institution - 402

Pavia, 27100, Italy

Location

Local Institution - 403

Reggio Emilia, 42100, Italy

Location

Servizio di Ematologia, A.O. - Arcispedale S.Maria Nuova

Reggio Emilia, 42100, Italy

Location

Policlinico Agostino Gemelli

Rome, 00168, Italy

Location

Azienda Ospedaliera San Giovanni Battista - Ospedale Molinette

Torino, 10126, Italy

Location

Local Institution - 406

Torino, 10126, Italy

Location

Local Institution - 704

Amsterdam, 1081 HV, Netherlands

Location

VU Medical Center

Amsterdam, 1081 HV, Netherlands

Location

Erasmus Medical Center

Rotterdam, 3015 CN, Netherlands

Location

Local Institution - 703

Rotterdam, 3015 CN, Netherlands

Location

Hopsital Germans Trias I Pujol

Badalona, 08918, Spain

Location

Hospital 12 de Octobre

Madrid, 28041, Spain

Location

Local Institution - 505

Madrid, 28041, Spain

Location

Clinica Universitaria de Navarra

Pamplona, 31008, Spain

Location

Local Institution - 501

Pamplona, 31008, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Local Institution - 503

Salamanca, 37007, Spain

Location

Hospital Doctor Peset

Valencia, 46017, Spain

Location

Local Institution - 506

Valencia, 46017, Spain

Location

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, 46026, Spain

Location

Local Institution - 504

Valencia, 46026, Spain

Location

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Multiple Myeloma

Interventions

durvalumab; Lenalidomide; Dexamethasone; Adrenal Cortex Hormones

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; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Limitations and Caveats

The study was placed on full clinical hold by the United States (US) Food and Drug Administration (FDA) on 05 Sep 2017. As the result, the study was closed for further enrollment, and all participants were discontinued from all study treatments (durvalumab, lenalidomide and dexamethasone). All participants were followed for second primary malignancies (SPMs), every 6 months for 5 years after the last participant has been enrolled as per protocol.

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please Email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2016
• First Posted: February 19, 2016
• Study Start: April 25, 2016
• Primary Completion: December 15, 2017
• Study Completion: September 6, 2022
• Last Updated: October 6, 2023
• Results First Posted: February 11, 2019

Record last verified: 2023-09

Locations

DE (5); CA (9); DK (6); IT (10); NL (4); ES (11); FI (2); US (7)