Nivolumab, Ixazomib, Cyclophosphamide, and Dexamethasone in Relapsed/Refractory Myeloma

NCT04119336 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 19-283
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 2

Brief Summary

This research is being done to assess the effectiveness and safety of the combination of nivolumab with ixazomib, cyclophosphamide, and dexamethasone in relapsed and refractory multiple myeloma.

Conditions

Relapsed Multiple Myeloma; Refractory Multiple Myeloma

Keywords

Refractory Multiple Myeloma; Relapsed Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR is defined as percentage of participants with complete response (CR) and partial response (PR) per International Myeloma Working Group (IMWG) criteria below. * CR = Negative immunofixation on serum and urine; disappearance of soft tissue plasmacytomas, and \<5% plasma cells in bone marrow * Stringent CR = Above definition plus normal FLC ration and absence of clonal cells in bone marrow by IHC or 2-4 color flow cytometry * PR = At least 50% reduction of serum M-protein and reduction in 24 urinary M-protein by at least 90% or to \<200 mg/24 h. If serum and urine M-protein unmeasurable, require at least 50% decrease in difference between involved and uninvolved FLC levels. If serum free light assay also unmeasurable, require at least 50% reduction in plasma cells, provided baseline was at least 30% * Very Good PR (VGPR) = Serum and urine M-protein detectable by immunofixation but not on electrophoresis, or \>90% reduction in serum M-protein plus urine M-protein level \<100 mg/24 h

  up to 8 months

Secondary Outcomes (1)

• Progression Free Survival

  Up to 2 years

Study Arms (1)

Nivolumab and Ixazomib

EXPERIMENTAL

\- Participants will receive Nivolumab, Ixazomib, Cyclophosphamide, and Dexamethasone on a 28-day cycle. * Oral: * Ixazomib given weekly on days 1, 8, 15 * Dexamethasone given weekly during cycle * Infused: * Nivolumab given once per cycle * Cyclophosphamide given on days 1, 8, 15 during cycle

Drug: Nivolumab; Drug: Ixazomib; Drug: Dexamethasone; Drug: Cyclophosphamide

Interventions

Nivolumab DRUG

Given intravenously once per cycle

Also known as: Opdivo

Nivolumab and Ixazomib

Ixazomib DRUG

Given orally on days 1, 8, 15.

Also known as: Ninlaro

Nivolumab and Ixazomib

Dexamethasone DRUG

Given orally on days 1, 8, 15, 22

Also known as: Decadron

Nivolumab and Ixazomib

Cyclophosphamide DRUG

Given intravenously on days 1, 8, 15.

Also known as: Cytoxan

Nivolumab and Ixazomib

Eligibility Criteria

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

You may qualify if:

• Previously treated relapsed and refractory multiple myeloma per International Myeloma Working Group consensus criteria (Rajkumar et al., 2011).
• Patients must have received at least three prior lines of therapy, including an immunomodulatory drug (e.g. lenalidomide, pomalidomide), a proteasome inhibitor (e.g. bortezomib, carfilzomib), and anti-CD38 monoclonal antibody (e.g. daratumumab)
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (see Appendix A).
• Age ≥ 18 years
• All laboratory assessments for eligibility should be performed within 21 days of initiation of protocol therapy unless otherwise specified.
• Measurable disease of multiple myeloma as defined by at least one of the following (IgD and IgA with monoclonal protein \< 0.5 g/dL may be permitted after discussion with PI):
• Serum monoclonal protein ≥ 0.5 g/dL (or quantitative IgA ≥ 1000 mg/dL), or
• ≥ 200 mg of monoclonal protein in the urine on 24-hour urine protein electrophoresis, and/or
• Serum free light chain ≥ 100 mg/L (10 mg/dL) and abnormal serum free kappa to serum free kappa light chain ratio
• ANC ≥ 1000/μL. G-CSF is not permitted within 14 days of screening.
• Platelet count ≥ 75,000/µL. Platelet transfusions are not permitted within 7 days of screening.
• Hemoglobin ≥ 8 g/dL. Red blood cell transfusions are permitted to meet eligibility criteria.
• Calculated creatinine clearance of ≥ 30 mL/min according to Cockroft-Gault equation.
• Adequate hepatic function, as evidenced by each of the following:
• Serum aspartate transaminase (ALT) and/or aspartate transaminase (AST) values \< 3 × the institutional upper limit of normal (ULN).

You may not qualify if:

• Prior therapy with ixazomib
• Prior therapy with any anti-PD1 antibody (e.g. nivolumab, pembrolizumab) or anti-PDL1 antibody (e.g. atezolizumab, avelumab, durvalumab)
• Participants who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) or with monoclonal antibodies 3 weeks of C1D1 or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier. Patients may have received dexamethasone within 2 weeks prior to C1D1.
• Participation in other clinical trials, including those with other investigational agents, within five half-lives prior to C1D1and throughout the duration of this trial. Prior treatment with an investigational agent within five half lives prior to C1D1 may be permitted after discussion with the PI.
• Concomitant high-dose corticosteroid use except chronic steroids (maximum dose 10 mg/day prednisone equivalent) if they are being given for disorders other than myeloma, e.g. adrenal insufficiency, rheumatoid arthritis, etc.
• Female patients who are lactating or have a positive serum pregnancy test during the screening period (within 21 days of C1D1).
• Prior history of malignancies, other than MM, unless the patient has been free of the disease for ≥ 3 years. Exceptions include the following if the patient has undergone complete resection:
• Basal or squamous cell carcinoma of the skin
• Carcinoma in situ of the cervix
• Ductal carcinoma in situ of the breast
• Incidental histologic finding of prostate cancer (T1a or T1b)
• Patients with another malignancy undergoing active treatment with the exception of non-melanoma skin cancer or in situ cervical cancer.
• Patients with plasma cell leukemia, POEMS syndrome, or amyloidosis are excluded from this trial.
• HIV infection.
• Active hepatitis B infection or active hepatitis C infection. Participants who have prior hepatitis C infection and who have received an antiviral treatment and show no detectable viral RNA for 6 months prior to screening are eligible.

Sponsors & Collaborators

• Andrew Yee, MD: lead
• Bristol-Myers Squibb: collaborator
• Takeda Pharmaceuticals North America, Inc.: collaborator

Study Sites (2)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Mass General/North Shore Cancer Center

Danvers, Massachusetts, 01923, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Nivolumab; ixazomib; Dexamethasone; Calcium Dobesilate; Cyclophosphamide

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Andrew Yee, MD
• Organization: Massachusetts General Hospital

AYEE1@mgh.harvard.edu

617-724-4000

Study Officials

• Andrew Yee, MD

  Massachusetts General Hospital

  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 5, 2019
• First Posted: October 8, 2019
• Study Start: February 14, 2020
• Primary Completion: November 12, 2020
• Study Completion: March 30, 2022
• Last Updated: August 21, 2023
• Results First Posted: August 21, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: MGH - Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (2)