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

Multiple Myeloma Clinical Trial

— POM MM 014  

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 Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01946477
• Other study ID #: CC-4047-MM-014
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 29, 2014
• Est. completion date: May 24, 2025

Study information

• Verified date: May 2023
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 186
• Est. completion date: May 24, 2025
• Est. primary completion date: May 24, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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] < 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 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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Pomalidomide

• Dexamethasone

• Daratumumab

Locations

Country	Name	City	State
Canada	Local Institution - 113	Calgary	Alberta
Canada	Local Institution - 139	Moncton	New Brunswick
Canada	Local Institution - 117	Montreal	Quebec
Canada	Local Institution - 140	St John's	Newfoundland and Labrador
Canada	Local Institution - 144	Surrey	British Columbia
Canada	Local Institution - 112	Toronto	Ontario
Canada	Local Institution - 148	Toronto	Ontario
Canada	Local Institution - 114	Vancouver	British Columbia
Japan	Local Institution - 205	Fukuoka
Japan	Local Institution - 208	Kamogawa
Japan	Local Institution - 204	Kyoto-city
Japan	Local Institution - 202	Nagoya
Japan	Local Institution - 203	Okayama
Japan	Local Institution - 206	Shibukawa-shi, Gunma-ken
Japan	Local Institution - 207	Toyohashi
Puerto Rico	Local Institution - 119	San Juan
United States	Montefiore Medical Center	Bronx	New York
United States	Local Institution - 135	Chattanooga	Tennessee
United States	Local Institution - 115	Cleveland	Ohio
United States	Local Institution - 121	Cleveland	Ohio
United States	Local Institution - 123	Cleveland	Ohio
United States	Local Institution - 138	Denver	Colorado
United States	Local Institution - 130	Durham	North Carolina
United States	Local Institution - 118	East Orange	New Jersey
United States	Local Institution - 134	Fairway	Kansas
United States	CR Wood Cancer Center	Glens Falls	New York
United States	Marin Oncology Associates	Greenbrae	California
United States	Saint John Hospital and Medical Center	Gross Pointe	Michigan
United States	Local Institution - 101	Hackensack	New Jersey
United States	Local Institution - 107	Hershey	Pennsylvania
United States	Cancer Specialist of North Florida	Jacksonville	Florida
United States	St. Luke's Hospital	Kansas City	Missouri
United States	Local Institution - 109	Los Angeles	California
United States	Local Institution - 124	Louisville	Kentucky
United States	Local Institution - 128	Lubbock	Texas
United States	Local Institution - 122	Mayfield Heights	Ohio
United States	Local Institution - 131	Nashville	Tennessee
United States	Local Institution - 127	Orlando	Florida
United States	Local Institution - 133	Pembroke Pines	Florida
United States	Texas Health Physicians Group	Plano	Texas
United States	Bay Area Cancer Research Group, LLC	Pleasant Hill	California
United States	Local Institution - 110	Saint Louis	Missouri
United States	Local Institution - 136	Saint Petersburg	Florida
United States	Local Institution - 106	Spokane	Washington
United States	Local Institution - 120	Stamford	Connecticut
United States	Cotton O'Neil Clinical Research, Hematology and Oncology	Topeka	Kansas
United States	University of Arizona Cancer Center	Tucson	Arizona
United States	Carroll Regional Cancer Center	Westminster	Maryland
United States	Local Institution - 108	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Canada,  Japan,  Puerto Rico, 

References & Publications (1)

Pelligra CG, Parikh K, Guo S, Chandler C, Mouro J, Abouzaid S, Ailawadhi S. Cost-effectiveness of Pomalidomide, Carfilzomib, and Daratumumab for the Treatment of Patients with Heavily Pretreated Relapsed-refractory Multiple Myeloma in the United States. Clin Ther. 2017 Oct;39(10):1986-2005.e5. doi: 10.1016/j.clinthera.2017.08.010. Epub 2017 Sep 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate (ORR)	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).	Approximately 2 years
Secondary	Overall survival (OS)	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.	Up to 7 years
Secondary	Progression-free survival (PFS)	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).	Up to 7 years
Secondary	Duration of Response (DoR)	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	Up to 7 years
Secondary	Time to Response (TTR)	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.	Up to 2 years
Secondary	Time to progression (TTP)	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 months after 100% enrollment and 5 years from Last Patient First Visit
Secondary	Adverse Events	Number of participants with adverse events including secondary primary malignancies.	Up to 7 years

External Links

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