Multiple myeloma - bone marrow cancer
Conditions
Interventions
The dose of durvalumab will depend on the cohort (Cohort -1: 750 mg
Cohort 1:
1500 mg
Cohort 2: 2250 mg
Cohort 3: 3000 mg). Additional/or and intermediate
dose levels may be added as deemed appropriate by the Dose Review Team (DRT).
The DRT consists of the Celgene medical monitor, Celgene lead safety
Sponsors
Celgene Corporation
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Subject is >= 18 years of age at the time of signing the informed consent form (ICF). 2. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted. 3. Subject is willing and able to adhere to the study visit schedule and other protocol requirements. 4. Subject has documented diagnosis of multiple myeloma and have measurable disease by serum protein electrophoresis (sPEP) or urine protein electrophoresis (uPEP): sPEP >= 0.5 g/dL or uPEP >= 200 mg/24 hours (except for subjects in the EMP sub-group). 5. Subject had at least 2 prior anti-myeloma regimens. (Note: Induction, bone marrow transplant with or without maintenance therapy is considered one regimen.) 6. Subject achieved at least a stable disease (SD) for at least 1 cycle of treatment to at least 1 prior anti-myeloma regimen before developing PD. 7. Subject had documented PD during or within 60 days after the last anti-myeloma regimen. 8. Subject received prior treatment with a lenalidomide-containing regimen for at least 2 consecutive cycles. 9. Subject received prior treatment with a proteasome inhibitor-containing regimen for at least 2 consecutive cycles. 10. Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2. 11. Females of childbearing potential (FCBP ) must: a. Have 2 negative pregnancy tests as verified by the investigator prior to starting study treatment. She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. This applies even if the subject practices true abstinence from heterosexual contact. b. Either practice true abstinence2 from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with, effective contraception without interruption, 28 days prior to starting study treatment, during the study therapy (including dose interruptions), and for at least 90 days after discontinuation of study treatment. c. Refrain from egg cell donation for at least 90 days after the final dose of durvalumab 12. Male subjects must: a. Either practice true abstinence2 (which must be reviewed on a monthly basis) or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 90 days following study treatment discontinuation, even if he has undergone a successful vasectomy. b. Refrain from sperm donation for at least 90 days after the final dose of durvalumab For subjects who will be in the Arm C extramedullarly plasmacytoma subgroup, the following includsion criterium will also apply: 13. Subject has radiologically measurable EMP disease (soft tissue of bone related) that is amenable to biopsy and subject agrees and consents to additional biopsy procedures as described in the protocol. These subjects do not need to have measurable disease by sPEP and/or uPEP.
Exclusion criteria
Exclusion criteria: 1. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study 2. Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study 3. Subject has any condition that confounds the ability to interpret data from the study 4. Subject has non-secretory or oligosecretory multiple myeloma (uitzondering voor patienten in de EMP sub-groep. 5. Subject has any of the following laboratory abnormalities: a. Absolute neutrophil count (ANC) 13.5 mg/dL (> 3.4 mmol/L) f. Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 × ULN g. Serum total bilirubin > 1.5 × ULN or > 3.0 mg/dL for subjects with documented Gilbert*s syndrome 6. Subject has 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 • Carcinoma in situ of the cervix • Carcinoma in situ of the breast • Incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) or prostate cancer that is curative 7. Subject had prior treatment with POM but did not achieve at least a SD with the POM-containing regimen 8. Subject had prior exposure to immunotherapy, including, but not limited to, other anti-CTLA-4,anti-PD-1, anti-PD-L1 mAbs, cell-based therapies, or cancer vaccines 9. Subject has history of organ or allogeneic stem cell transplantation 10. Subject has or had clinical evidence of central nervous system (CNS) or pulmonary leukostasis, disseminated intravascular coagulation, or CNS multiple myeloma 11. Subject has history of anaphylaxis or hypersensitivity to thalidomide, lenalidomide, POM, or dex 12. Subject had rash >= Grade 3 during prior thalidomide, lenalidomide, or POM therapy 13. Subject has incidence of gastrointestinal disease that may significantly alter the absorption of POM 14. Subject has known or suspected hypersensitivity to the excipients contained in the formulation of durvalumab, POM, or dex 15. Subject has received any of the following within the last 14 days of initiating study treatment: a. Plasmapheresis b. Major surgery (as defined by the investigator) c. Radiation therapy other than local therapy for myeloma associated bone lesions d. Use of any systemic anti-myeloma drug therapy 16. Subject has received prior treatment with a monoclonal antibody within 5 half-lives of initiating study treatment 17. Subject has used any investigational agents within 28 days or 5 half-lives (whichever is longer) of initiating study treatment 18. Subject has peripheral neuropathy >= Grade 2 19. Subject has any one of the following: a. Clinically significant abnormal electrocardiogram (ECG) finding at screening b. Congestive heart failure (New York Heart Association Class III or IV) c. Myocardial infarction within 12 months prior to starting study treat
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary objective of the study is to determine the recommended dose and regimen of durvalumab either as monotherapy or in combination with POM +/- dex in subjects with RRMM. | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary objectives are to: * Evaluate the safety and preliminary efficacy of durvalumab monotherapy and in combination with POM +/- dex in subjects with RRMM * Evaluate the PK of durvalumab and POM with or without dex in subjects with RRMM The exploratory objectives are to: * Determine the immunogenicity of durvalumab as monotherapy and when given in combination with POM +/- dex in subjects with RRMM * Establish PK/Pd relationship, explore Pd, mechanistic, and predictive biomarkers of durvalumab and POM as single agents and when given in combination in subjects with RRMM * Evaluate minimal residual disease (MRD) and its correlation to clinical outcome measures * Evaluate additional measures of efficacy of durvalumab monotherapy and in combination with POM +/- dex in subjects with RRMM | — |
Countries
Netherlands
Outcome results
None listed