Clinical Trials /

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

NCT03374085

Description:

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.

Related Conditions:
  • Multiple Myeloma
  • Non-Secretory Plasma Cell Myeloma
  • Plasma Cell Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Safety, PK and Efficacy Study of CC-92480 Monotherapy and in Combination With Dexamethasone in Subjects With Relapsed and Refractory Multiple Myeloma (RRMM)
  • Official Title: A Phase 1/2 Multicenter, Open-label Study to Assess the Safety, Pharmacokinetics and Efficacy of CC-92480 Monotherapy and in Combination With Dexamethasone in Subjects With Relapsed and Refractory Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: CC-92480-MM-001
  • SECONDARY ID: U1111-1205-3650
  • SECONDARY ID: 2017-001236-19
  • NCT ID: NCT03374085

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
CC-92480Administration of CC-92480 in combination with dexamethasone
DexamethasoneAdministration of CC-92480 in combination with dexamethasone

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Administration of CC-92480 in combination with dexamethasoneExperimentalEscalating doses of CC-92480 and in combination with a fixed dose of dexamethasone administered according to different dosing schedules
  • CC-92480
  • Dexamethasone
Administration of CC-92480 monotherapyExperimentalEscalating doses of CC-92480 Monotherapy administered according to different dosing schedules
  • CC-92480

Eligibility Criteria

        Inclusion Criteria:

          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. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.

          5. 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

               -  ≥ 200 mg/24 hour urine collection by uPEP or

               -  Serum FLC levels > 100 mg/L (milligrams/liter) involved light chain and an
                  abnormal kappa/lambda (κ/λ) 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.

          6. All subjects must have:

               -  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.

          7. 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 µmol/L).

               -  PT/INR < 1.5 x ULN and partial thromboplastin time (PTT) < 1.5 x ULN, (for
                  subjects not receiving therapeutic anticoagulation).

          8. 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).

          1. 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:

          1. Subject has a 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 non-secretory multiple myeloma.

          5. Subject has refractory primary multiple myeloma (ie, no history of at least a minor
             response to a prior treatment regimen).

          6. Subject has plasma cell leukemia or active leptomeningeal myelomatosis.

          7. Subject has documented, systemic light chain amyloidosis or Polyneuropathy,
             Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes (POEMS)
             Syndrome.

          8. Subject has immunoglobulin class M (IgM) myeloma.

          9. 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.

         10. Subject is undergoing dialysis.

         11. Subjects with peripheral neuropathy ≥ Grade 2.

         12. Subjects with gastrointestinal disease that may significantly alter the absorption of
             CC-92480.

         13. 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.

         14. Concurrent administration of strong CYP3A modulators; concurrent administration of
             proton-pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, pantoprazole) ≤ 2
             weeks prior to starting CC-92480.

         15. 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.

         16. Subject had major surgery ≤ 2 weeks prior to starting CC-92480. Note: Subjects must
             have recovered from any clinically significant effects of recent surgery.

         17. Subject is a pregnant or nursing female, or intends to become pregnant or donate ova
             during participation in the study.

         18. Subject has known human immunodeficiency virus (HIV) infection.

         19. Subject has known active chronic hepatitis B or C virus (HBV/HCV) infection.

         20. Subject has a history of concurrent second cancer requiring ongoing systemic
             treatment.

         21. 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.

         22. Subject has a history of anaphylaxis to thalidomide, lenalidomide, pomalidomide or
             dexamethasone.

         23. 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.

         24. 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.

         25. 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).

         26. Subject is unable or unwilling to undergo protocol required venous thromboembolism
             (VTE) prophylaxis.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse Events (AEs)
Time Frame:From enrollment until at least 28 days after completion of study treatment
Safety Issue:
Description:Number of participants with AEs to CC-92480 and/or dexamethasone (Type, frequency, seriousness, severity and relationship of AEs to CC-92480 and dexamethasone; changes from baseline in clinically-relevant physical findings, vital signs, selected laboratory analytes, ECGs).

Secondary Outcome Measures

Measure:Overall response rate (ORR)
Time Frame:Up to approximately 3 years
Safety Issue:
Description:Best response ≥ partial response (PR), according to the IMWG Uniform Response Criteria
Measure:Time to response (TTR)
Time Frame:Up to approximately 3 years
Safety Issue:
Description:Time from 1st dose of CC-92480 to the first documentation of response ≥ PR.
Measure:Duration of response (DOR)
Time Frame:Up to approximately 3 years
Safety Issue:
Description:Time from the first documentation of response (≥ PR) to the first documentation of PD or death.
Measure:Progression free survival
Time Frame:Up to approximately 3 years
Safety Issue:
Description:Time from 1st dose of CC-92480 to the first occurrence of disease progression or death from any cause.
Measure:Overall survival (OS)
Time Frame:Up to approximately 3 years
Safety Issue:
Description:Time from first dose of CC-92480 to death due to any cause
Measure:Adverse Events (AEs)
Time Frame:Time from first dose of CC-92480 to death due to any cause
Safety Issue:
Description:Number of participants with AEs to CC-92480 and/or dexamethasone (Type, frequency, seriousness, severity and relationship of AEs to CC-92480 and dexamethasone; changes from baseline in clinically-relevant physical findings, vital signs, selected laboratory analytes, ECGs).

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Celgene

Trial Keywords

  • Multiple Myeloma
  • Safety
  • Efficacy
  • CC-92480
  • Relapsed
  • Refractory

Last Updated

July 14, 2021