Source: https://archimaid.fr/index.php?action=show&id=1060
Timestamp: 2020-07-09 23:29:46
Document Index: 389980917

Matched Legal Cases: ['art 1', 'art 2', 'art 1', 'art 1', 'art 2', 'art 2', 'art 1', 'art 1', 'art 1', 'art 1', 'art2', 'art 2', 'art 2', 'art 2', 'art 2']

Etude : CC-220-MM-001 / - ARCHIMAID
Etude : CC-220-MM-001 /
Acronyme : CC-220-MM-001
Titre : A Phase 1b/2a Multicenter, Open-label, Dose-escalation Study to Determine the Maximum Tolerated Dose, Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of CC-220 as Monotherapy and in Combination With Other Treatments in Subjects With Multiple Myeloma
This is a multicenter, multi-country, open-label, Phase 1b/2a dose-escalation study consisting of two parts:
- dose escalation (Part 1) for CC-220 MonoT, CC-220 in combination with DEX, CC-220 in combination with DEX and DARA, CC-220 in combination with DEX and BTZ and CC-220 in combination with DEX and CFZ;
- and the expansion of the RP2D (Part 2) for CC-220 MonoT, CC-220 in combination with DEX (DoubleT) for Relapsed Refractory Multiple Myeloma and CC-220 in combination with DEX and BTZ for Newly Diagnosed Multiple Myeloma.
- Experimental: Cohort A: CC-220 Monotherapy - Part 1
- Experimental: Cohort B: CC-220 in combination with Dexamethasone - Part 1
- Experimental: Cohort C: CC-220 Monotherapy - Part 2
- Experimental: Cohort D: CC-220 in combination with Dexamethasone - Part 2
- Experimental: Cohort E: CC-220 with DEX and daratumumab (DARA) - Part 1
- Experimental: Cohort F: CC-220 with DEX and bortezomib - Part 1
- Experimental: Cohort G1-CC-220 in combination with CFZ and DEX -Part 1
Intravenous (IV) CFZ (Carfilzomib)administered at a starting dose of 20 mg/m2 on C1D1; and at a dose specified by cohort dose level thereafter on days 1, 8, 15 of each 28-day cycle
Oral DEX (Dexamethasone) on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects ≤ 75 years old, the DEX dose will be 40 mg. For subjects > 75 years old, the DEX dose will be 20 mg
- Experimental: Cohort G2 - CC-220 in combination with CFZ and DEX - Part 1
- Experimental: CohortI-CC-220 in combination with DEX in post BCMA RRMM-Part2
- Experimental: CohortJ1:CC-220 in combination with DEX and BTZ in NDMM-Part 2
Oral CC-220 at Recommended Phase 2 Dose from Day 1-14 of each 21-day cycle (Cycle 1 to 8) and from Day 1-21 of each 28-day cycle (Cycle 9 and above).
Oral DEX at Cycles 1 to 8, 20 mg (≤ 75 years old) or 10 mg (> 75 years old) on Days 1, 2, 4, 5, 8, 9, 11 and 12 of each 21-day cycle and Cycles ≥ 9, 40 mg (≤ 75 years old) or 20 mg (> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle.
Subcutaneous BTZ at dose 1.3 mg/m2 on Days 1, 4, 8 and 11 at Cycle 1-8 of each 21-day cycle.
- Experimental: CohortJ2:CC-220 in combination with DEX and BTZ in NDMM-Part 2
Oral CC-220 at Recommended Phase 2 Dose from Day 1-14 of each 21-day cycle.
Oral DEX at 20 mg/day (≤ 75 years old) or 10 mg/day (> 75 years old) for Cycles 1 to 6 on Days 1, 2, 4, 5, 8, 9, 11 and 12 of a 21-day cycle.
Subcutaneous BTZ at dose 1.3 mg/m2 on Days 1, 4, 8 and 11 at Cycle 1-6 of each 21-day cycle.
- Establish maximum tolerated doses (MTDs) of CC-220 as monotherapy and in combination with other treatment [ Time Frame: Approximately 1 year ]
- Establish Recommended Phase 2 doses (RP2Ds) of CC-220 as monotherapy and in combination with other treatment [ Time Frame: Approximately 1 year ]
- Overall response rate (ORR) of CC-220 in combination with DEX in Cohort D in Part 2 [ Time Frame: Approximately 3 years ]
- Time to Response (TTR) [ Time Frame: Approximately 3 years ]
- Pharmacokinetics ‐AUC 0-τ [ Time Frame: Approximately 1 year ]
- Pharmacokinetics ‐Cmax [ Time Frame: Approximately 1 year ]
- Pharmacokinetics ‐Tmax [ Time Frame: Approximately 1 year ]
- Pharmacokinetics ‐t1/2 [ Time Frame: Approximately 1 year ]
- Pharmacokinetics ‐CLss/F [ Time Frame: Approximately 1 year ]
- Pharmacokinetics ‐Vss/F [ Time Frame: Approximately 1 year ]
- Overall Survival (OS) in Part 2 RRMM cohorts [ Time Frame: Approximately 3 years ]
- Very good partial response or better rate (VGPR) [ Time Frame: Approximately 4 years ]
Critères d'inclusion : 1. Subject is ≥18 years of age at the time of signing the informed consent form (ICF)
4. Subjects 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
5. Subjects in Cohorts A to E 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.
11. A female of childbearing potential (FCBP) is a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months) and must:
a) Have two 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 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 two forms of contraception: one highly effective, and one
additional effective (barrier) measure of contraception without interruption 28
days prior to starting investigational product, during the study treatment
(including dose interruptions), and for at least 28 days after the last dose of CC220 or 90 days after the last dose of DARA (for Cohort E) or BTZ (for Cohort F), whichever is longer. Contraception requirements are detailed in the Protocol Appendix D.
12. Male subjects must: Practice true abstinence* (which must be reviewed on a monthly basis and source documented) 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 the last dose of study treatment, even if he has undergone a successful vasectomy.
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.
Critères de non-inclusion : 1. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study
* Absolute neutrophil count (ANC) <1,000/μL
* Platelet count <75,000/μL Corrected serum calcium >13.5 mg/dL (>3.4 mmol/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 ([CrCl] <50 mL/min) or requiring dialysis would be excluded
* 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
* 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
* Clinically significant abnormal electrocardiogram (ECG) finding at Screening
* Myocardial infarction within 12 months prior to starting IP
* Unstable or poorly controlled angina pectoris, including the Prinzmetal variant of angina pectoris
* 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 including
grapefruit, St. John’s Wort or related products within two weeks prior to dosing and during the course of study.
19. Subject is a female who is pregnant, nursing or breastfeeding, or who intends to become pregnant during the participation in the study
ClinicalTrials (anglais) : https://clinicaltrials.gov/ct2/show/record/NCT02773030
EU clinical trial register (anglais) : https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-000860-40/GB