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

Phase 2

Recruiting

• Conditions: bone marrow cancer; Multiple myeloma; 10035227

• Registration Number: NL-OMON54734
• Lead Sponsor: Celgene Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 2024-09-09

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 56

Inclusion Criteria

1. Subject is >=18 years of age 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. 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 at least 3 prior myeloma 
regimens.

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. 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 <br

Exclusion Criteria

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 (creatine 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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Recommended Dose and Regimen in Part 1:<br>Establish the maximum tolerated doses (MTDs) and or Recommended Phase 2 doses<br>(RP2D) of CC-220 monotherapy, in combination with DEX, and in combination with<br>DEX and daratumumab (C220Dd), in combination with DEX and bortezomib (C220Vd),<br>and in combination with DEX and carfilzomib (CC-220Kd).<br><br>Overall response rate (ORR) in Cohort D:<br>Tumor response, including progressive disease (PD) according to the<br>International Myeloma Working Group (IMWG) Uniform Response Criteria (Kumar,<br>2016) in CC-220 in combination with DEX</p>