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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Celgene Corp.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

9 Aug 2016 → ongoing

Decision date (initial)

2024-07-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Celgene Corporation

External identifiers

EU CT number

2024-510799-19-00

EudraCT number

2016-000860-40

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

Part 1
To determine the maximum tolerated doses (MTDs) and/or RP2D of CC-
220 as monotherapy (MonoT), in combination with DEX (DoubleT), in
combination with DEX and daratumumab (DARA) (CC-220Dd), in
combination with DEX and bortezomib (BTZ) (CC-220Vd), and in
combination with DEX and carfilzomib (CFZ) (CC-220Kd) in subjects with RRMM.
Part 2
To determine the efficacy of CC-220 in combination with DEX (Double T) in subjects with RRMM in Cohort D, as measured by overall response rate (ORR).

Secondary objectives 6

1. To evaluate the safety of CC-220 as MonoT, DoubleT, CC-220Dd, CC- 220Vd, and CC-220Kd in subjects with RRMM
2. To evaluate the preliminary efficacy and safety of CC-220Vd, and CC- 220Dd in subjects with NDMM, including subjects who are eligible for ASCT and subjects who are not eligible for ASCT
3. To evaluate additional efficacy parameters of CC-220 in combination with DEX including time-to-response (TTR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) in subjects with RRMM in Cohort D
4. To assess the preliminary efficacy of CC-220 as MonoT, DoubleT, CC- 220Dd, CC220Vd, and CC-220Kd in subjects with RRMM in Part 1
5. To assess the preliminary efficacy and safety of CC-220 in combination with DEX in subjects with RRMM who have received prior B-cell maturation antigen (BCMA) targeted therapy
6. To evaluate the pharmacokinetics (PK) of CC-220 in subjects with RRMM and NDMM

Conditions and MedDRA coding

Multiple Myeloma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 18

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 pomalidomidecontaining 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.

Exclusion criteria 19

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 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Establish the maximum tolerated doses and or Recommended Phase 2 doses of CC-220 monotherapy, in combination with DEX, and in combination with DEX and daratumumab in combination with DEX and bortezomib, and in combination with DEX and carfilzomib.
2. Overall response rate (ORR) in Cohort D -Tumor response, including progressive disease (PD) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria (Kumar, 2016) in CC-220 in combination with DEX

Secondary endpoints 8

1. Safety - Type, frequency, seriousness and severity of adverse events (AEs) (and AEs of special interest) and relationship of AEs to investigational product
2. Very good partial response or better rate (VGPR) - Tumor response, including progressive disease (PD) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria for subjects who achieved VGPR or better.
3. Overall response rate (ORR) - Tumour response, including progressive disease (PD) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria for subjects who achieved partial response (PR) or better
4. Time to response (TTR) - Time from enrollment to the first documentation of response (PR or greater).
5. Duration of response (DOR)- Time from the first documentation of response (PR or greater) to the first documentation of PD.
6. Progression free survival (PFS) - Time from the first dose of investigational product (IP) to the first documentation of PD or death from any cause, whichever occurs first.
7. Overall Survival (OS) in Part 2 RRMM cohorts- Time from first dose of IP to death due to any cause.
8. Pharmacokinetic (PK) parameters- PK of CC-220, and as appropriate, its R-enantiomer CC-17195 in plasma, eg, area under the plasma concentration-time curve from time zero to tau, where tau is the dosing interval (AUC(TAU)), maximum plasma concentration of drug (Cmax), time to Cmax (Tmax)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 16

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Celgene Corp.

Sponsor organisation

Celgene Corp.

Address

Route 206 And Province Line Road

City

Princeton

Postcode

08543-4000

Country

United States

Scientific contact point

Organisation

Celgene Corp.

Contact name

GSM-CT

Public contact point

Organisation

Celgene Corp.

Contact name

GSM-CT

Third parties 7

Locations

5 EU/EEA countries · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 41 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications