A Phase 3, Multicenter, Randomized, Open-label Study to Compare the Efficacy and Safety of Pomalidomide (POM), Bortezomib (BTZ) and Low-Dose Dexamethasone (LD-DEX) versus Bortezomib and Low-Dose Dexamethasone in Subjects with Relapsed or Refractory Multiple Myeloma (MM)

Study ID
STU 122012-003

Cancer Related
Yes

Healthy Volunteers
No

Study Sites

  • UT Southwestern Ambulatory Services
  • UT Southwestern University Hospital—St. Paul
  • UT Southwestern University Hospital– Zale Lipshy

Contact
James Pond
214-648-7030
blake.pond@utsouthwestern.edu

Principal Investigator
Larry Anderson

Summary

This study is a multicenter, randomized, open-label, phase 3 study comparing the efficacy and safety of PoM + BTZ + LD-DeX (Treatment arm a) versus BTZ + LD-DeX (Treatment arm B) in subjects with relapsed or refractory MM. For Treatment arm a, the dose of PoM and iV BTZ are based on the results from the Phase 1 dose escalation MTD study for the combination of PoM + BTZ + LD-DeX (CC-4047-MM-005). in the CC-4047-MM-005 trial, the pomalidomide dose was escalated from 1 mg to 4 mg in the first 4 dose cohorts while combining with 1 mg/m2 bortezomib, and in the last dose cohort pomalidomide was given at 4 mg in combination with 1.3 mg/m2 bortezomib. no DLTs were observed in any of the dose cohorts in the CC-4047-MM-005 study, and therefore, in this study using the same PoM + BTZ + LD-DeX combination therapy,the pomalidomide and bortezomib doses are 4 mg and 1.3 mg/m2, respectively. a total of 782 subjects will be randomized equally (1:1 ratio) into the two treatment arms (391 subjects in each arm)

Treatment arm a: Subjects randomized to Treatment arm a (PoM + BTZ + LD-DeX) will receive the following medications by 21-day treatment cycle:
* oral PoM 4 mg/day on Days 1 to 14 of each 21-day treatment cycle
* iV BTZ
* For Cycles 1 x 8: 1.3 mg/m2/dose on Days 1, 4, 8, and 11 of a 21-day cycle
* For Cycles 9 onwards: 1.3 mg/m2/dose on Days 1 and 8 of a 21-day cycle
* oral DeX
* For Cycles 1 to 8, 20 mg/day ([LessThanorequalTo] 75 years old) or 10 mg/day ([Greater Than] 75 years old) on
Days 1, 2, 4, 5, 8, 9, 11 and 12 of a 21-day cycle.
* For Cycles 9 and onward, 20 mg/day ([LessThanorequalTo] 75 years old) or 10 mg/day ([Greater Than] 75 years
old) on Days 1, 2, 8, and 9 of a 21-day cycle.

Treatment arm B: Subjects randomized to Treatment arm B (BTZ + LD-DeX) will receive the following medications by 21-day treatment cycle:
* iV BTZ
* For cycles 1 x 8: 1.3 mg/m2/dose on Days 1, 4, 8, and 11 of a 21-day cycle
For cycles 9 onwards: 1.3 mg/m2/dose on Days 1 and 8 of a 21-day cycle
* oral DeX
* For Cycles 1 to 8, 20 mg/day ([LessThanorequalTo] 75 years old) or 10 mg/day ([Greater Than] 75 years old) on
Days 1, 2, 4, 5, 8, 9, 11 and 12 of a 21-day cycle.
* For Cycles 9 and onward, 20 mg/day ([LessThanorequalTo] 75 years old) or 10 mg/day ([Greater Than] 75 years
old) on Days 1, 2, 8, and 9 of a 21-day cycle.

Randomization
Subjects who meet all eligibility criteria will be randomized to either Treatment arm a (PoM + BTZ + LD-DeX) or Treatment arm B (BTZ + LD-DeX) with equal probability (1:1 randomization ratio). all subjects in Treatment arm a will be maintained on the pregnancy prevention program for the duration of the study as outlined in appendix e. The randomization procedure will be accomplished by a validated iVRS/iWRS, stratified by the following factors: 1) age ([LessThanorequalTo] 75 years old vs. [Greater Than] 75 years old); 2) number of prior anti-MM regimens (1 vs. [Greater Than]1); 3) Beta-2 microglobulin ([MiCRo-SYMBoL]2M) at screening ([Less Than] 3.5 mg/L vs. [GreaterThanorequalTo] 3.5 mg/L - [LessThanorequalTo] 5.5 mg/L vs. [Greater Than] 5.5 mg/L). a randomization authorization number is needed to initiate the iVRS/iWRS prior to subject enrollment.

Participant Eligibility

Subjects must satisfy the following criteria to be enrolled in the study:
1. Must be >= 18 years at the time of signing the informed consent form.
2. The subject must understand and voluntarily sign an informed consent document prior to any study-related assessments/procedures.
3. Must be able to adhere to the study visit schedule and other protocol requirements.
4. Subjects must have documented diagnosis of multiple myeloma and have measurable disease by serum or urine protein electrophoresis (sPEP or uPEP): sPEP >= 0.5 g/dL or uPEP >= 200 mg/24 hours.
5. All subjects must have had at least 1 but no greater than 3 prior anti-myeloma regimens. (note: induction, bone marrow transplant with or without maintenance therapy is considered one regimen.)
6. All subjects must have documented disease progression during or after their last antimyeloma therapy.
7. All subjects must have received prior treatment with a lenalidomide-containing regimen for at least 2 consecutive cycles.
8. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
9. Females of childbearing potential (FCBP[?]) must agree to utilize two reliable forms of contraception simultaneously or practice complete abstinence from heterosexual contact for at least 4 weeks before starting study treatment, while participating in the study (including dose interruptions), and for at least 4 weeks after study treatment discontinuation, and must agree to regular pregnancy testing during this timeframe.
10. Females must agree to abstain from breastfeeding during study participation and 4 weeks after study treatment discontinuation.
11. Males must agree to use a latex or synthetic condom during any sexual contact with FCBP while participating in the study and for 4 weeks following discontinuation from this study, even if he has undergone a successful vasectomy.
12. Males must also agree to refrain from donating sperm while on pomalidomide and for 4 weeks after discontinuation from this study treatment.
13. All subjects must agree to refrain from donating blood while on study treatment and for 4 weeks after discontinuation from this study treatment.
14. All subjects must agree not to share medication.