A study to decide what is the highest dose of CC-220 to take alone and with dexamethasone to assess the side effects, effectiveness and how the body deals with the drug in patients with multiple myeloma that recurs or is resistant to already tried medicines by patients.
- Conditions
- RELAPSED AND REFRACTORY MULTIPLE MYELOMAMedDRA version: 19.0Level: LLTClassification code 10067095Term: Multiple myeloma progressionSystem Organ Class: 100000004864MedDRA version: 16.1Level: HLTClassification code 10028229Term: Multiple myelomasSystem Organ Class: 100000004851Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-000860-40-ES
- 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
- 106
Subjects must satisfy the following criteria to be enrolled in the study:
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. Subjects must have a documented diagnosis of MM and have measurable disease by serum and/or urine protein electrophoresis (sPEP or uPEP): sPEP ?0.5 g/dL or uPEP ?200 mg/24 hours
5. All subjects 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)
6. All subjects must have received prior treatment with at least 2 consecutive cycles of a lenalidomide or pomalidomide-containing regimen
7. All subjects must have received prior treatment with at least 2 consecutive cycles of a proteasome inhibitor or a proteasome inhibitor-containing regimen
8. All subjects must have documented disease progression on or within 60 days from the last dose of their last myeloma therapy
9. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2
10. Females of childbearing potential (FCBP) must:
a. Have a negative pregnancy test as verified by the Investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after the end of IP. This applies even if the subject practices true abstinence* from heterosexual contact.
b. Either commit to true abstinence* 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 investigational product, during the study therapy (including dose interruptions), and for 28 days after discontinuation of study therapy.
11. Male subjects must:
a. Practice true abstinence* (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 28 days following investigational product discontinuation, even if he has undergone a successful vasectomy.
* True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. [Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.]
12. Males must agree to refrain from donating sperm while on CC-220 and for 90 days after discontinuation from IP.
13. All subjects must agree to refrain from donating blood while on IP and for 90 days after discontinuation from IP.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 46
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 or oligosecretory multiple myeloma
5. Subjects with Plasma Cell leukemia
6. Any of the following laboratory abnormalities
·Absolute neutrophil count (ANC) <1,000/?L
·Hemoglobin <8 g/dL (<4.9 mmol/L)
·Platelet count <75,000/?L 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 (24-hour creatinine clearance [CrCl] <50 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 or DEX
11. Subject has known or suspected hypersensitivity to the excipients contained in the formulation of CC-220 or DEX
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 within 28 days or 5 half-lives (whichever is longer) of initiating IP
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 days prior to the first dose of IP. The following are exceptions to this criterion:
·Intranasal, inhaled, topical or local steroid injections (eg, intra-articular injection)
·Systemic corticosteroids at physiologic doses that do not exceed 10 mg/day of prednisone or equivalent
·Steroids as premedication for hypersensitivity reactions (eg, computed tomography [CT] scan premedication)
16. Subject has taken a strong inhibitor or inducer of CYP3A4/5 at least one week prior to dosing and during the course of study and grapefruit or related products ?1 week prior to dosing and intends to eat these products t
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determine the maximum tolerated doses (MTDs) of CC-220 as monotherapy (MonoT) and in combination with dexamethasone (DEX) (DoubleT) in subjects with RRMM;Secondary Objective: ·To evaluate the safety of CC-220 as MonoT and in combination with DEX (DoubleT) in subjects with RRMM<br>·To estimate the preliminary efficacy of CC-220 as MonoT and in combination with DEX (DoubleT) in subjects with RRMM<br>·To evaluate the pharmacokinetics (PK) of CC-220 in subjects with RRMM;Primary end point(s): Recommended Dose - Establish the maximum tolerated doses (MTDs) of CC-220 monotherapy and in combination with dexamethasone;Timepoint(s) of evaluation of this end point: The endpoint of MTD is estimated after cycle 1 for each subject in the dose escalation phase. <br><br>Further details are available in the clinical study protocol and Table 4 - Table of Events page 39-42 of the protocol
- Secondary Outcome Measures
Name Time Method