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 (PoM + BTZ + DeX), the dose was based on the results from the CC-4047-MM-005 (MM-005) Phase 1 dose escalation MTD study in which bortezomib was administered via iV infusion. in the MM-005 study, the maximum planned dose (MPD), PoM (4 mg) + iV BTZ (1.3 mg /m2) and DeX (20 mg subjects [LessThanorequalTo] 75 years old/10 mg subjects [Greater Than] 75 years old) was reached without any DLTs. Considering an early PoM single agent MTD study (Richardson, 2013) as well as the findings in MM-005, the MPD was determined to be the optimal dose for the triple combination therapy. With the optimal dose determined, MM-007 was initiated using the MPD dose for the combination of PoM + BTZ + LD-DeX (with iV BTZ).

During the conduct of the MM-005 study, subcutaneous (SQ) BTZ was approved as an alternative administration method for BTZ (23 Jan 2013). The SQ BTZ was reported to have a decreased incidence of neurotoxicity versus the iV BTZ (Velcade[RegisteredTM] Prescribing information, 2012). To explore the SQ route of BTZ administration in combination with PoM and DeX, the MM-005 protocol was amended to add a cohort of 6 subjects at the MPD/optimal dose for the
combination of PoM + BTZ + LD-DeX with BTZ administered via SQ injection. Based on the safety, efficacy and PK data for this SQ BTZ cohort (see Section 1.4) and general adoption in medical practice of SQ BTZ as standard of care due to decreased neurotoxicity, BTZ administration is now to be SQ for both arms in the MM-007 study (Treatment arm a and B).

Subjects consented to the original MM-007 protocol can continue with iV BTZ or switch to SQ BTZ at the discretion of the treating physician. Subjects randomized into MM-007 under iV BTZ treatment will not be replaced.

Subjects will be randomized to Treatment arm a or Treatment arm B at a 1:1 ratio.

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
* 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:
* 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).

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.