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Pomalidomide in Combination With Low-dose Dexamethasone or Pomalidomide in Combination With Low-dose Dexamethasone and Daratumumab in Subjects With Relapsed or Refractory Multiple Myeloma Following Lenalidomide-based Therapy in the First or Second Line Setting

NCT01946477

Description:

This trial will evaluate the efficacy and safety of combination of pomalidomide (POM) and low-dose dexamethasone (LD-Dex) (Cohort A) or the combination of pomalidomide (POM) , daratumumab (DARA) and low-dose dexamethasone (LD-Dex) (Cohort B) in subjects with relapsed or refractory multiple myeloma who have received a first or second line treatment of lenalidomide-based therapy. This trial will test the hypothesis for Cohort A that the proportion of patients will have an Overall Response Rate (ORR) of > 30 % to reveal that Pomalidomide is efficacious in pretreated patients who are refractory to lenalidomide. This trial will test the hypothesis for Cohort B that the proportion of patients will have an Overall Response Rate (ORR) of > 70 % to reveal that POM+DARA+LD-Dex is efficacious in pretreated patients who are refractory to lenalidomide. This trial will test the hypothesis for Cohort C that the proportion of patients will have an Overall Response Rate (ORR) of >60% to reveal that POM+DARA+LD-Dex is efficacious in pretreated patients who are refractory to lenalidomide. This treatment will be in only Japanese patients.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pomalidomide in Combination With Low-dose Dexamethasone or Pomalidomide in Combination With Low-dose Dexamethasone and Daratumumab in Subjects With Relapsed or Refractory Multiple Myeloma Following Lenalidomide-based Therapy in the First or Second Line Setting
  • Official Title: A Phase 2, Multicenter, Multi-cohort, Open-label Study of Pomalidomide in Combination With Low-dose Dexamethasone or Pomalidomide in Combination With Low-dose Dexamethasone and Daratumumab in Subjects With Relapsed or Refractory Multiple Myeloma Following Lenalidomide Based Therapy in the First or Second Line Setting.

Clinical Trial IDs

  • ORG STUDY ID: CC-4047-MM-014
  • NCT ID: NCT01946477

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
PomalidomideCC-4047Pomalidomide + dexamethasone
DexamethasonedexPomalidomide + dexamethasone
DaratumumabPomalidomide + Dexamethasone + Daratumumab

Purpose

This trial will evaluate the efficacy and safety of combination of pomalidomide (POM) and low-dose dexamethasone (LD-Dex) (Cohort A) or the combination of pomalidomide (POM) , daratumumab (DARA) and low-dose dexamethasone (LD-Dex) (Cohort B) in subjects with relapsed or refractory multiple myeloma who have received a first or second line treatment of lenalidomide-based therapy. This trial will test the hypothesis for Cohort A that the proportion of patients will have an Overall Response Rate (ORR) of > 30 % to reveal that Pomalidomide is efficacious in pretreated patients who are refractory to lenalidomide. This trial will test the hypothesis for Cohort B that the proportion of patients will have an Overall Response Rate (ORR) of > 70 % to reveal that POM+DARA+LD-Dex is efficacious in pretreated patients who are refractory to lenalidomide.

Detailed Description

      A phase 2, multicenter, multi-cohort, open-label study of pomalidomide in combination with
      low-dose dexamethasone or pomalidomide in combination with low-dose dexamethasone and
      daratumumab in subjects with relapsed or refractory multiple myeloma following lenalidomide
      based therapy in the first or second line setting.

      This trial will assess, Overall Response Rate (ORR), Overall Survival (OS), Progression-Free
      Survival (PFS), Duration of Response (DoR), Time to Response (TTR), Time to Progression(TTP)
      and safety.
    

Trial Arms

NameTypeDescriptionInterventions
Pomalidomide + dexamethasoneExperimentalEach subject enrolled in the study will take oral pomalidomide (4 mg) once daily on Days 1-21 and dexamethasone 40 mg/day (< 75 years old) or 20 mg/day (>75 years old) on Days 1, 8, 15 and 22 of a 28-day cycle.
  • Pomalidomide
  • Dexamethasone
Pomalidomide + Dexamethasone + DaratumumabExperimentalEach subject enrolled in the study will take oral pomalidomide (4 mg) once daily on Days 1-21 and dexamethasone 40 mg/day (< 75 years old) or 20 mg/ day (>75 years old) on Days 1, 8, 15 and 22 of a 28-day cycle and daratumumab administered intravenously (IV) at a starting dose of 16 mg/kg at following schedule: Days 1, 8, 15, and 22 of a 28-day cycle for Cycle 1 and Cycle 2 Days 1 and 15 for Cycle 3 through Cycle 6 Day 1 for Cycle 7 and each cycle thereafter until disease progression
  • Pomalidomide
  • Dexamethasone
  • Daratumumab

Eligibility Criteria

        Inclusion Criteria:

        - Subjects must satisfy the following criteria to be enrolled in the study:

          1. Adults (age ≥ 18 years at the time of signing the ICD) with documented diagnosis of
             MM and measurable disease (serum M-protein ≥ 0.5 g/dL or urine M-protein ≥ 200 mg/24
             hours).

          2. Subjects enrolling in Cohort A (Pom+LD-dex) must have received 2 prior treatment
             lines of anti-myeloma therapy. Subjects enrolling in Cohort B (Pom+Dara+LD-dex) must
             have received 1 or 2 prior treatment lines of anti-myeloma therapy.

          3. All subjects must have received prior treatment with LEN or a LEN-containing regimen
             for at least 2 consecutive cycles as the most recent treatment regimen.

          4. All subjects must have documented disease progression during or after their last
             antimyeloma therapy.

          5. Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status
             score of 0, 1, or 2.

          6. Subjects must understand and voluntarily sign an ICD prior to any study related
             assessments/procedures being conducted.

          7. Subjects must be able to adhere to the study visit schedule and other protocol
             requirements.

          8. All subjects must provide an adequate bone marrow sample at screening that
             definitively evaluates the presence or absence of myelodysplastic changes.

          9. Females with child-bearing potential (FCBP†) must agree to use 2 reliable forms of
             contraception* simultaneously or practice complete abstinence from heterosexual
             contact for at least 28 days before starting study drug, while participating in the
             study (including during dose interruptions), and for at least 28 days after study
             treatment discontinuation and must agree to regular pregnancy testing during this
             timeframe. For subjects enrolled in Cohort B, pregnancy prevention and testing will
             continue until 3 months after last dose of daratumumab.

         10. Females must agree to abstain from breastfeeding during study participation and 28
             days after study drug discontinuation. Female subjects enrolled in Cohort B must
             agree to abstain from breastfeeding and donating eggs during study participation and
             until 3 months after last dose of daratumumab.

         11. Males must agree to use a latex condom during any sexual contact with FCBP while
             participating in the study and for 28 days following discontinuation from this study,
             even if he has undergone a successful vasectomy. Male subjects enrolled in Cohort B
             must agree to use a latex condom during any sexual contact with FCBP while
             participating in the study and until 3 months after last dose of daratumumab.

         12. Males must also agree to refrain from donating semen or sperm during the treatment
             phase and for 28 days after discontinuation from this study treatment. Male subjects
             enrolled in Cohort B must also agree to refrain from donating semen or sperm during
             the treatment phase and until 3 months after last dose of daratumumab.

         13. All subjects must agree to refrain from donating blood while on study therapy and for
             28 days after discontinuation from this study treatment.

         14. All subjects must agree not to share medication.

        Exclusion Criteria:

        The presence of any of the following will exclude a subject from study enrollment:

          1. Any of the following laboratory abnormalities:

               -  Absolute neutrophil count < 1,000/μL

               -  Platelet count < 75,000/μL for subjects in whom < 50% of bone marrow nucleated
                  cells are plasma cells; or a platelet count < 30,000/μL for subjects in whom ≥
                  50% of bone marrow nucleated cells are plasma cells.

               -  Severe renal impairment (Creatinine Clearance [CrCl] < 30 mL/min) requiring
                  dialysis.

               -  Corrected serum calcium > 11.5 mg/dL (> 2.8 mmol/L)

               -  Hemoglobin < 8 g/dL (< 4.9 mmol/L; prior red blood cell transfusion or
                  recombinant human erythropoietin use is permitted)

               -  Serum SGOT/AST or SGPT/ALT > 3.0 x the upper limit of normal (ULN)

               -  Serum total bilirubin > 2.0 mg/dL (34.2 μmol/L); or > 3.0 x ULN for subjects
                  with hereditary benign hyperbilirubinemia

          2. Prior history of malignancies, other than MM, unless the subject has been free of the
             disease for ≥ 5 years. Allowed exceptions include the following:

               -  Basal or squamous cell carcinoma of the skin

               -  Carcinoma in situ of the cervix or breast

               -  Incidental histological finding of prostate cancer (TNM [tumor, nodes,
                  metastasis] stage of T1a or T1b)

          3. Previous therapy with pomalidomide or daratumumab

          4. Hypersensitivity to thalidomide, LEN, or dex (this includes ≥ Grade 3 rash during
             prior thalidomide or LEN therapy)

          5. Subjects who received an allogeneic bone marrow or allogeneic peripheral blood stem
             cell transplant less than 12 months prior to initiation of study treatment and who
             have not discontinued immunosuppressive treatment for at least 4 weeks prior to
             initiation of study treatment and are currently dependent on such treatment.

          6. Subjects with any one of the following:

               -  Congestive heart failure (NY Heart Association Class III or IV)

               -  Myocardial infarction within 12 months prior to starting study treatment

               -  Unstable or poorly controlled angina pectoris, including Prinzmetal's variant
                  angina pectoris

          7. Subjects who received any of the following within 14 days of initiation of study
             treatment:

               -  Major surgery (kyphoplasty is not considered major surgery)

               -  Use of any anti-myeloma drug therapy

          8. Use of any investigational agents within 28 days or 5 half-lives (whichever is
             longer) of treatment, unless approved by the sponsor.

          9. Incidence of gastrointestinal disease that may significantly alter the absorption of
             Pomalidomide.

         10. Subjects unable or unwilling to undergo antithrombotic prophylactic treatment

         11. Any serious medical condition, laboratory abnormality, or psychiatric illness that
             would prevent the subject from signing the ICD

         12. Pregnant or breastfeeding females

         13. Known human immunodeficiency virus (HIV) positivity; active infectious hepatitis A,
             B, or C; or chronic hepatitis B or C

         14. For subjects enrolling in Cohort B - Subject has known allergies, hypersensitivity to
             mannitol, corticosteroids, monoclonal antibodies or human proteins, or their
             excipients (refer to the Daratumumab IB), or known sensitivity to mammalian-derived
             products.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate (ORR)
Time Frame:Approximately 2 years
Safety Issue:
Description:The primary endpoint will be the Overall Response Rate (ORR) by modified International Myeloma Working Group (mIMWG) criteria and will be based on the best response prior to the time frame. ORR will consist of the responses of PR or better (Complete Response -CR, Very Good Partial Response-VGPR or Partial Response- PR).

Secondary Outcome Measures

Measure:Overall survival (OS)
Time Frame:Up to 7 years
Safety Issue:
Description:Overall survival will be calculated as the time from start of treatment until the time of death from any cause. If no death is recorded the subject will be censored at the time the subject was last known to be alive.
Measure:Progression-free survival (PFS)
Time Frame:Up to 7 years
Safety Issue:
Description:Progression-free survival will be calculated as the time from start of treatment until the time of PD (as determined by the site Investigator based on the mIMWG criteria) or death from any cause on study treatment, whichever comes first. Subjects not experiencing a documented progression will be censored at the time of their last response assessment (or at the time of trial enrollment if no assessment was conducted).
Measure:Duration of Response (DoR)
Time Frame:Up to 7 years
Safety Issue:
Description:Duration of response, calculated for responders only, is defined as time from the initial documented response (PR or better) to the first confirmed PD or until death from any cause. Subjects without a documented progression will be censored at the time of their last response assessment
Measure:Time to Response (TTR)
Time Frame:Up to 2 years
Safety Issue:
Description:Time to response, calculated for responders only, is calculated as the time from the start of treatment to the first documented response (PR or better) based on modified International Working Group ( mIMWG) criteria.
Measure:Time to progression (TTP)
Time Frame:6 months after 100% enrollment and 5 years from Last Patient First Visit
Safety Issue:
Description:Time to progression will be calculated as the time from start of treatment until PD (as determined by the site Investigator based on the mIMWG criteria) or death from progressive disease. Subjects not experiencing a documented progression will be censored at the time of their last response assessment (or at the time of trial enrollment if no assessment was conducted).
Measure:Adverse Events
Time Frame:Up to 7 years
Safety Issue:
Description:Number of participants with adverse events including secondary primary malignancies.

Details

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

Trial Keywords

  • Multiple Myeloma, MM, cancer, oncology, hematology, plasma, neoplasm, plasmacytoma

Last Updated

December 28, 2016