A Safety PK and Efficacy Study of CC-92480 Monotherapy and in Combination With Dexamethasone in Subjects With Relapsed and Refractory Multiple Myeloma (RRMM)

  • STATUS
    Recruiting
  • End date
    May 6, 2022
  • participants needed
    201
  • sponsor
    Celgene
Updated on 24 July 2021
cancer
bone marrow transplant
measurable disease
maintenance therapy
bone marrow procedure
dexamethasone
lenalidomide
progressive disease
neutrophil count
proteasome inhibitor
refractory multiple myeloma
pomalidomide
immunotherapeutic agent

Summary

This is an open-label, multi-center, international, Phase 1/2 study to assess the safety, PK and efficacy of CC-92480 monotherapy and in combination with dexamethasone in subjects with relapsed and refractory multiple myeloma (RRMM).

RRMM patient previously treated with at least 3 prior regimens including lenalidomide or pomalidomide, a proteasome inhibitor and a CD38 antibody will be eligible.

Details
Condition Multiple Myeloma, Lymphoproliferative Disorder, Lymphoproliferative disorders, multiple myeloma (mm)
Treatment Dexamethasone, CC-92480
Clinical Study IdentifierNCT03374085
SponsorCelgene
Last Modified on24 July 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Subject is 18 years of age at the time of signing the informed consent form (ICF)
All subjects must have
Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted
Subject is willing and able to adhere to the study visit schedule and other protocol requirements
Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2
Subjects must have a documented diagnosis of MM and measurable disease at enrollment. Measurable disease is defined as
M-protein quantities 0.5 g/dL by sPEP or
mg/24 hour urine collection by uPEP or
Serum FLC levels > 100 mg/L (milligrams/liter) involved light chain and an abnormal kappa/lambda (/) ratio in subjects without measurable serum or urine M-protein or
For subjects with immunoglobulin class A (IgA), myeloma whose disease can only be reliably measured by quantitative immunoglobulin measurement, a serum IgA level 0.50 g/dL
Received at least 3 prior anti-myeloma regimens including at least 2 consecutive cycles of lenalidomide, pomalidomide, a proteasome inhibitor, a glucocorticoid and a CD38 antibody (note: induction with or without bone marrow transplant and with or without maintenance therapy is considered one regimen)
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 are eligible as long as they have documented disease progression following CAR-T therapy
In addition to criteria above (a and b), subjects enrolled in Part 2 must have disease refractory to an immunomodulatory agent (lenalidomide and/or pomalidomide), a glucocorticoid, a proteasome inhibitor, and a CD38 antibody. Refractory is defined as disease that is nonresponsive on therapy (failure to achieve minimal response or development of progressive disease), or progresses within 60 days of last dose
Subjects must have the following laboratory values
Absolute neutrophil count (ANC) 1.25 x 109/L without growth factor support for 7 days ( 14 days for pegfilgrastim). ANC of 1.00 x 109/L is permitted for the dose expansion cohorts (Part 2)
Hemoglobin (Hgb) 8 g/dL
Platelets (plt) 75 x 109/L without transfusion for 7 days
Corrected serum calcium 13.5 mg/dL ( 3.4 mmol/L)
Creatinine clearance (CrCl) based on Cockcroft-Gault formula 45 mL/min
AST/SGOT and ALT/SGPT 3.0 x upper limit of normal (ULN)
Serum bilirubin 1.5 x ULN or < 3.0 mg/dL for subjects with documented Gilbert's syndrome
Uric acid 7.5 mg/dL (446 mol/L)
PT/INR < 1.5 x ULN and partial thromboplastin time (PTT) < 1.5 x ULN, (for subjects not receiving therapeutic anticoagulation)
Females of childbearing potential (FCBP) must
Have two negative pregnancy tests 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 discontinuation of CC-92480. This applies even if the subject practices true abstinence from heterosexual contact
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 reliable forms of contraception as defined in the PPP and provided to the subject at the time of informed consent, without interruption, 28 days prior to starting CC-92480, during the study therapy (including during dose interruptions), and for 28 days after discontinuation of study therapy
Note: A female of childbearing potential (FCBP) is a female who: 1) has
achieved menarche at some point and, 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)
Male subjects must
Practice true abstinence (which must be reviewed on a monthly basis) or agree
to use of a condom during sexual contact with a pregnant female or a female of
childbearing potential while participating in the study (even during dose
interruptions) and for at least 3 months following CC-92480 discontinuation in
accordance with the PPP provided to the subject at the time of informed
consent, 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 coitus interruptus (withdrawal) are not acceptable methods of contraception. 2. Males must agree to refrain from donating sperm while on CC-92480 for 90 days after its discontinuation. Females must agree to refrain from donating ova while on CC-92480 for 28 days after its discontinuation. 3. All subjects must agree to refrain from donating blood while on CC-92480 and for 28 days after its discontinuation

Exclusion Criteria

Subject has a significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study
Subject is unable or unwilling to undergo protocol required venous thromboembolism (VTE) prophylaxis
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
Subject has any condition that confounds the ability to interpret data from the study
Subject has non-secretory multiple myeloma
Subject has refractory primary multiple myeloma (ie, no history of at least a minor response to a prior treatment regimen)
Subject has plasma cell leukemia or active leptomeningeal myelomatosis
Subject has documented, systemic light chain amyloidosis or Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes (POEMS) Syndrome
Subject has immunoglobulin class M (IgM) myeloma
Part 1: Subject has a history of allogeneic bone marrow transplantation. Part 2: Subject has a history of allogeneic bone marrow transplantation within 6 months prior to first dose. Subject should not have ongoing graft-versus-host disease (GVHD) requiring systemic immunosuppression
Subject is undergoing dialysis
Subjects with peripheral neuropathy Grade 2
Subjects with gastrointestinal disease that may significantly alter the absorption of CC-92480
Subject has impaired cardiac function or clinically significant cardiac disease, including any of the following
LVEF < 45% as determined by ECHO or MUGA scan at Screening
Complete left bundle branch, bifascicular block or other clinically significant abnormal electrocardiographic (ECG) finding at Screening
A prolongation of QT interval on Screening ECG as defined by repeated demonstration of a QTc interval >480 milliseconds (ms) using Fridericia's QT correction formula; a history of or current risk factors for Torsades de Pointe (eg, heart failure, hypokalemia, or a family history of Long QT Syndrome); and concurrent administration of medications that prolong the QT/QTc interval
Congestive heart failure (New York Heart Association Class III or IV)
Myocardial infarction 6 months prior to starting CC-92480
Unstable or poorly controlled angina pectoris, including the Prinzmetal variant of angina pectoris
Concurrent administration of strong CYP3A modulators; concurrent administration of proton-pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, pantoprazole) 2 weeks prior to starting CC-92480
Subject had prior systemic myeloma treatment with an investigational anti-myeloma agent (eg, anti-PD-1, anti-PD-L1) 5 half-lives prior to starting CC-92480 (not applicable for subjects who had CAR-T as last prior regimen); subject had prior exposure to approved myeloma therapies (including therapeutic monoclonal antibodies such as anti-CD38 or anti-SLAM-7) 5 half-lives or within 4 weeks prior to starting CC-92480 whichever is shorter
Subject had major surgery 2 weeks prior to starting CC-92480. Note: Subjects must have recovered from any clinically significant effects of recent surgery
Subject is a pregnant or nursing female, or intends to become pregnant or donate ova during participation in the study
Subject has known human immunodeficiency virus (HIV) infection
Subject has known active chronic hepatitis B or C virus (HBV/HCV) infection
Subject has a history of concurrent second cancer requiring ongoing systemic treatment
Subjects has a history of prior malignancy other than MM, except if the subject has been free of disease for 3 years OR the subject had one of the following noninvasive malignancies treated with curative intent without known recurrence
Basal or squamous cell carcinoma of the skin
Carcinoma in situ of the cervix or breast
Stage 1 bladder cancer
Incidental histological findings of localized prostate cancer such as tumor stage 1a or 1b (T1a or T1b) using the Tumor/Node/Metastasis (TNM) classification of malignant tumors OR prostate cancer that has been treated with curative intent
Subject has a history of anaphylaxis to thalidomide, lenalidomide, pomalidomide or dexamethasone
Subject has known or suspected hypersensitivity to the excipients (excipients include silica dimethyl silylate, anhydrous colloidal silicon dioxide, mannitol, fumaric acid and stearic acid) contained in the formulation of CC-92480 or dexamethasone
Subject has undergone either of the following within 14 days of initiating CC-92480
Plasmapheresis
Radiation therapy other than local therapy for symptomatic relief of MM associated bone lesions
Subject has received immunosuppressive medication within 14 days prior to the first dose of CC-92480. The following are exceptions to this criterion
Intranasal, inhaled, topical or local corticosteroid injections (eg, intra-articular injection)
Systemic corticosteroids at doses that do not exceed 10 mg/day of prednisone or the equivalent
Steroids as premedication for hypersensitivity reactions (eg, computed tomography [CT] scan premedication)
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