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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 05/30/2020.

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

Clinicaltrials.gov identifier NCT01946477

Recruitment Status Recruiting

First Posted September 19, 2013

Last update posted April 9, 2020

Study Description

Brief summary:

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.

  • Condition or Disease:Multiple Myeloma
  • Intervention/Treatment: Drug: Pomalidomide
    Drug: Dexamethasone
    Drug: Daratumumab
  • Phase: Phase 2
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.

Study Design
  • Study Type: Interventional
  • Estimated Enrollment: 156 participants
  • Allocation: Non-Randomized
  • Intervention Model: Parallel Assignment
  • Masking: None (Open Label) ()
  • Primary Purpose: Treatment
  • 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.
  • Actual Study Start Date: May 2014
  • Estimated Primary Completion Date: May 2025
  • Estimated Study Completion Date: May 2025
Arms and interventions
Arm Intervention/treatment
Experimental: Pomalidomide + Dexamethasone + Daratumumab
Each 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
Drug: Pomalidomide


Drug: Dexamethasone


Drug: Daratumumab
Experimental: Pomalidomide + dexamethasone
Each 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.
Drug: Pomalidomide


Drug: Dexamethasone
Outcome Measures
  • Primary Outcome Measures: 1. Overall response rate (ORR) [ Time Frame: Approximately 2 years ]
    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: 1. Overall survival (OS) [ Time Frame: Up to 7 years ]
    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.
  • 2. Progression-free survival (PFS) [ Time Frame: Up to 7 years ]
    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).
  • 3. Duration of Response (DoR) [ Time Frame: Up to 7 years ]
    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
  • 4. Time to Response (TTR) [ Time Frame: Up to 2 years ]
    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.
  • 5. Time to progression (TTP) [ Time Frame: 6 months after 100% enrollment and 5 years from Last Patient First Visit ]
    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).
  • 6. Adverse Events [ Time Frame: Up to 7 years ]
    Number of participants with adverse events including secondary primary malignancies.
Eligibility Criteria
  • Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No
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 and Cohort C
(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 and
Cohort C, 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
and Cohort C 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 and Cohort C 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 and Cohort C 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] 11.5 mg/dL (> 2.8 mmol/L)

- Hemoglobin < 8 g/dL ( 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 more than 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 including for the treatment of multiple myeloma
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 oral
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 preclude participation in the study, or interfere with interpretation
of the study results

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

All subjects will be tested for hepatitis B surface antigen (HBsAg), hepatitis B
surface antibody (antiHBs), and hepatitis B core antibody (antiHBc). Subjects
with the following serological testing are considered not eligible:

- HBsAg positive

- HBsAg negative, anti-HBs positive and/or anti-HBc positive and detectable
viral DNA

Note:

- Subjects who are HBsAg negative, anti-HBs positive, and/or anti-HBc
positive, viral DNA negative are eligible. For these subjects, DNA
monitoring and prophylactic medication for HBV reactivation are recommended
per local practice.

- Subjects who are seropositive because of hepatitis B virus vaccination are
eligible (anti-HBs positive, anti-HBc negative, and HBsAg negative).

All subjects will be tested for hepatitis C antibody. Subjects are not eligible
if known seropositive for hepatitis C virus.

Note:

• Subjects who are hepatitis C antibody positive but show no detectable viral RNA
for 6 months prior to initiation of study treatment are eligible.

14. For subjects enrolling in Cohort B and Cohort C - 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.

Contacts and Locations
Contacts

Contact: Associate Director Clinical Trial Disclosure, MD 1-888-260-1599 clinicaltrialdisclosure@celgene.com

Locations
Show 49 Study Locations
Sponsors and Collaborators

Celgene

Investigators

Study Director: Amit Agarwal, MD Celgene Corporation

More Information