Etude : CC-220-MM-001 /



ATTENTION : pour chaque essai clinique, les éléments affichés ci-dessous ne sont pas exhaustifs, et le protocole fourni par le promoteur reste l’unique document à consulter pour mener à bien un essai clinique sur centre. Pour plus d'informations, contactez le référent du territoire concerné.


Acronyme
Nom
Traitement
Type d'étude
MÀJ
Présentation de l'étude
Acronyme : CC-220-MM-001

Nom :

Traitement :

Type d'étude : Hors ciblage moléculaire

Dernière MÀJ : 10/02/2020
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
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

Spécialité : Tissus lymphoïde, hématopoïétique et apparentés
Localisation : C90 - Myélome multiple et tumeurs malignes à plasmocytes
Schéma
Phase
Stade
Ligne(s)
Informations complémentaires
Schéma : Study design:
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.

Study arms:
- Experimental: Cohort A: CC-220 Monotherapy - Part 1
Oral CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle

- Experimental: Cohort B: CC-220 in combination with Dexamethasone - Part 1
Oral CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle.
For subjects ≤ 75 years old, oral DEX 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects >75 years old, DEX will be administered at 20 mg on Days 1, 8,15, and 22 of each 28-day cycle. Subjects who surpass the age of 75 years while on treatment may be switched to the 20 mg QD dosage based on the investigator's best judgment.

- Experimental: Cohort C: CC-220 Monotherapy - Part 2
Oral CC-220 at Recommended Phase 2 dose (RP2D) from Day 1-21 of each 28-day cycle

- Experimental: Cohort D: CC-220 in combination with Dexamethasone - Part 2
Oral CC-220 at Recommended Phase 2 dose (RP2D) from Day 1-21 of each 28-day cycle
Oral DEX 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects >75 years old, DEX will be administered at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle.

- Experimental: Cohort E: CC-220 with DEX and daratumumab (DARA) - Part 1
Oral CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle.
Oral DEX for subjects ≤ 75 years old at 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects >75 years old, oral DEX at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle.
Intravenous DARA at dose 16 mg/kg on Days 1, 8, 15, and 22 at cycle 1-2, Days 1, 15 at cycle 3-6, and Day 1 at cycle ≥7 of each 28-day cycle.

- Experimental: Cohort F: CC-220 with DEX and bortezomib - Part 1
Oral CC-220 at dose specified by cohort dose level from Day 1-14 of each 21-day cycle.
Oral DEX for subjects ≤ 75 years old at 40 mg on Days 1, 8, and 15 of each 21-day cycle. For subjects >75 years old, oral DEX at 20 mg on Days 1, 8, and 15 of each 21-day cycle.
Subcutaneous BTZ at dose 1.3 mg/m^2 on Days 1, 4, 8 and 11 at cycle 1-8, and Days 1, 8 at cycle ≥9 of each 21-day cycle.

- Experimental: Cohort G1-CC-220 in combination with CFZ and DEX -Part 1
Oral CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle
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
Oral CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle
Intravenous (IV) CFZ administered at a starting dose of 20 mg/m2 on C1D1; and at a dose level specified by cohort dose level thereafter Days 1, 2, 8, 9, 15, 16 of each 28-day cycle
Oral DEX on Days 1, 2, 8, 9, 15, 16, 22, 23 of each 28-day cycle. The DEX dose will be 20 mg

- Experimental: CohortI-CC-220 in combination with DEX in post BCMA RRMM-Part2
Oral CC-220 at Recommended Phase 2 dose (RP2D) from Day 1-21 of each 28-day cycle
Oral DEX 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects >75 years old, oral DEX will be administered at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle.

- 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.


Current primary outcome:
- 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 ]
RP2D is defined as the dose selected for phase 2 based on safety, pharmacokinetics and biomarker data from phase 1 of the study.
- Overall response rate (ORR) of CC-220 in combination with DEX in Cohort D in Part 2 [ Time Frame: Approximately 3 years ]

Current secondary outcomes:
- Adverse Events (AEs) [ Time Frame: Approximately 3 years ]
- Overall response rate (ORR) [ Time Frame: Approximately 3 years ]
- Time to Response (TTR) [ Time Frame: Approximately 3 years ]
- Duration of Response (DOR) [ 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 ]
- Progression-free Survival (PFS) [ Time Frame: Approximately 3 years ]
- 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 ]

Phase : I/II

Stade : NA

NA
Informations libres de droit
Critères d'inclusion
Critères de non-inclusion
Informations libres de droit
Critères d'inclusion et de non-inclusion
Critères d'inclusion : 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 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 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.
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. For Part 2 (Cohort C and Cohort D), all subjects must have received prior treatment with at least 2 consecutive cycles of an anti-CD38 therapy or an anti-CD38-containing regimen
9. All subjects must have documented disease progression on or within 60 days from the last dose of their last myeloma therapy
10. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2
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.
* 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.]
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.

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
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 or amyloidosis
6. Any of the following laboratory abnormalities:
* 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
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 Cohort E), or bortezomib (for Cohort F)
11. Subject has known or suspected hypersensitivity to the excipients contained in the formulation of CC-220, DEX, daratumumab (for Cohort E), or bortezomib (for Cohort F)
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
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 including
grapefruit, St. John’s Wort or related products within two weeks prior to dosing and during the course of study.
17. Subject known to test positive for human immunodeficiency virus (HIV), chronic or active hepatitis B, or active hepatitis A or C
18. Subject is unable or unwilling to undergo protocol required thromboembolism prophylaxis
19. Subject is a female who is pregnant, nursing or breastfeeding, or who intends to become pregnant during the participation in the study

Additional Exclusion Criteria for Cohort E (CC-220 + DARA + DEX):
20. Subject has known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) 50% of predicted normal. Note that forced expiratory testing (FEV1) is required for subjects suspected of having COPD and subjects must be excluded if FEV1 is < 50% of predicted normal
21. Subject has received previous allogeneic stem cell transplant; or received autologous stem cell transplantation within 12 weeks prior to enrollment
22. Subject has known moderate or severe persistent asthma, or currently has uncontrolled asthma of any classification
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT02773030
Promoteur :
CELGENE
Type de sponsor : Industriel
United States – Summit, NJ 86 Morris Avenue Summit, NJ 07901
00000 HORS FRANCE

Coordonnateur :
Centre investigateur
Investigateur
TEC / ARC / IDE
État
MÀJ
Informations relatives aux investigateurs
Centre investigateur :
Centre Hospitalier Universitaire de Lille - 2 Avenue Oscar Lambret - 59000 LILLE

Investigateur :
Professeur Thierry FACON

TEC / ARC / IDE :
Secrétariat de recherche
fanny.miquel@
chru-lille.fr
03.20.44.57.13

Ouverture de l'essai : OUVERT

MAJ : 10/02/2020