A study to decide what is the highest dose of CC-220 to take alone and with other standard of care treatments to assess the side effects, effectiveness and how the body deals with the drug in patients with multiple myeloma
- Conditions
- MULTIPLE MYELOMAMedDRA version: 21.1Level: LLTClassification code 10067095Term: Multiple myeloma progressionSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 16.1Level: HLTClassification code 10028229Term: Multiple myelomasSystem Organ Class: 100000004851Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-000860-40-NL
- Lead Sponsor
- Celgene Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 536
Subjects must satisfy the following criteria:
1. Subject is =18 years of age at the time of signing the 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. All subjects in RRMM cohorts must have a documented diagnosis of MM and have measurable disease defined as: a. M-protein (serum and/or urine protein electrophoresis (sPEP or uPEP)): sPEP =0.5 g/dL or uPEP =200 mg/24 hours and/or
b. Light chain MM without measurable disease in the serum or urine: serum immunoglobulin free light chain = 10 mg/dL (100 mg/L) and abnormal serum immunoglobulin kappa lambda free light chain ratio
5. Subjects in Cohorts A,B,C, E, G1 and G2 must have received at least 2 prior myeloma regimens (note: induction with or without bone marrow transplant and with or without maintenance therapy is considered one regimen). Subjects in Cohort F must have received at least 1 prior myeloma regimen. Subjects in Cohorts D and I must have received at least 3 prior myeloma regimens.
6. All subjects in RRMM cohorts must have received prior treatment with at least 2 consecutive cycles of a lenalidomide or pomalidomide-containing regimen. Subjects in Cohort D must have received prior treatment with at least 2 consecutive cycles of a lenalidomide-containing regimen and at least 2 consecutive cycles of a pomalidomide-containing regimen.
7. All subjects in RRMM cohorts must have received prior treatment with at least 2 consecutive cycles of a proteasome inhibitor or a proteasome inhibitor-containing regimen
8. For Part 2 RRMM cohorts (Cohorts C,D,and I) all subjects must have received prior treatment with at least 2 consecutive cycles of a CD38 antibody or a CD38 antibody-containing regimen
9. All subjects in RRMM cohorts must have documented disease progression on or within 60 days from the last dose of their last myeloma therapy. Subjects who had CAR T therapy as their last myeloma therapy must have documented disease progression.
10. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2
11. Please refer to the protocol page 68 for a discussion on the criteria for a female of childbearing potential.
12. Please refer to the protocol page 68 for a discussion on the conditions of practicing true abstinence for male subjects.
13. Males must agree to refrain from donating sperm while on study treatment, during dose interruptions and for at least 90 days following last dose of study treatment.
14. All subjects must agree to refrain from donating blood while on study treatment, during dose interruptions and for at least 28 days following the last dose of study treatment.
15. All male and female subjects must follow all requirements defined in the Pregnancy Prevention Program. See Appendix D of the protocol for CC-220 Pregnancy Prevention Plan for Subjects in Clinical Trials
16. Subjects in Cohort D must have received prior treatment with at least 2 consecutive cycles of a glucocorticoid-containing regimen.
17. Subjects in Cohort D must be refractory to an ID agent, a proteasome inhibitor, a glucocorticoid and a CD38 antibody.
18.Subjects in Cohort I must have received prior treatment with a BCMA targeted therapy.
Additional Inclusion Criteria for Part 2 Cohorts J1 and J2 (CC-220 + BTZ + DEX in NDMM) and Cohort K (CC-220 + DARA + DEX in NDMM) are further detailed in the protocol.
A
The presence of any of the following will exclude a subject from enrollment:
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 nonsecretory multiple myeloma
5. Subjects with Plasma Cell leukemia or amyloidosis
6. Any of the following laboratory abnormalities
·Absolute neutrophil count (ANC) <1,000/µL
·Platelet count <75,000/µL for Part 1. For Part 2; platelet count < 75,000/µL for subjects in whom < 50% of bone marrow nucleated cells are plasma cells; otherwise platelet count < 50,000/µL(transfusions are not permitted to achieve minimum platelet counts)
·Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L)
·Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) or serum glutamic pyruvic transaminase (SGPT)/alanine aminotransferase (ALT) =2.0 x upper limit of normal (ULN)
·Serum total bilirubin and alkaline phosphatase >1.5 x ULN
·Subjects with serious renal impairment (creatinine clearance [CrCl] <30 mL/min) or requiring dialysis would be excluded
7. Subjects with peripheral neuropathy =Grade 2
8. Subjects with gastrointestinal disease that may significantly alter the absorption of CC-220
9. Subjects with a 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 noninvasive 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 histological findings of prostate cancer such as T1a or T1b using the Tumor/Node/Metastasis (TNM) classification of malignant tumors or prostate cancer that is curative
10. Subject has a history of anaphylaxis or hypersensitivity to thalidomide, lenalidomide, pomalidomide, DEX, daratumumab (for Cohorts E and K), bortezomib (for Cohorts F, J1 and J2) or carfilzomib (for Cohorts G1 and G2)
Subject has known or suspected hypersensitivity to the excipients contained in the formulation of CC-220, DEX, daratumumab (for Cohorts E and K), bortezomib (for Cohorts F, J1 and J2) or carfilzomib (for Cohorts G1 and G2).
11. Contraindications to the other treatment regimens, as per local prescribing information
12. Subject has received any of the following within the last 14 days of initiating IP:
·Plasmapheresis
·Major surgery (as defined by the Investigator)
·Radiation therapy other than local therapy for MM associated bone lesions
·Use of any systemic myeloma drug therapy
13, Subject has been treated with an investigational agent (ie, an agent not commercially available) within 28 days or 5 half-lives (whichever is longer) of initiating IP. Not applicable for subjects who had CAR T as last prior regimen.
14. Subject has any one of the following:
·Clinically significant abnormal electrocardiogram (ECG) finding at Screening
·Congestive heart failure (New York Heart Association Class III or IV)
·Myocardial infarction within 12 months prior to starting IP
·Unstable or poorly controlled angina pectoris, including the Prinzmetal variant of angina pectoris
15. Subject has current or prior use of immunosuppressive medication within 14
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method