Protocol Summary

Protocol No.: OCR15752

Sponsor Protocol No.: OP-103

Study Title
OP-103 A Randomized, Controlled, Open-Label, Phase 3 Study of Melflufen/Dexamethasone Compared with Pomalidomide/Dexamethasone for Patients with Relapsed Refractory Multiple Myeloma who are Refractory to Lenalidomide (OP-103)

Principal Investigator(s)
Moreb, Jan

Objective
This is a randomized, controlled, open-label, Phase 3 multicenter study which will enroll patients with RRMM following 2-4 lines of prior therapy and who are refractory to lenalidomide in the last line of therapy as demonstrated by disease progression on or within 60 days of completion of the last dose of lenalidomide. Patients will receive either melflufen+dex or pomalidomide+dex.

Description
This is a randomized, controlled, open-label, Phase 3 multicenter study which will enroll patients with RRMM following 2-4 lines of prior therapy and who are refractory to lenalidomide in the last line of therapy as demonstrated by disease progression on or within 60 days of completion of the last dose of lenalidomide.
Patients will be randomized to either one of two arms:
Arm A: Melflufen 40 mg on Day 1 and dexamethasone 40 mg on Days 1, 8, 15 and 22 of each 28-day cycle.
Arm B: Pomalidomide 4 mg daily on Days 1 to 21 and dexamethasone 40 mg on Days 1, 8, 15 and 22 of each 28-day cycle.
Patients ≥ 75 years of age will have a reduced dose of dexamethasone of 20 mg on Days 1, 8, 15 and 22 for both Arm A and Arm B.
Patients may receive treatment until such time as there is documented disease progression, unacceptable toxicity or the patient/treating physician determines it is not in the patient's best interest to continue.
Dose modifications and delays in therapy may be implemented based on patient tolerability as detailed in the protocol. In the event of a cycle delay, unrelated to dexamethasone toxicity, it is recommended to continue dexamethasone weekly.

Phase: Phase III

Age Group: Adult

Scope: National

Treatment
Arm A: Melflufen+Dexamethasone
Melflufen 40 mg i.v. on Day 1 and dexamethasone 40 mg on Days 1, 8, 15 and 22 of each 28-day cycle. Patients are to be treated until confirmed progression, unacceptable toxicity or the patient or investigator decides it is not in the patients best interest to continue.

Arm B: Pomalidomide+Dexamethasone
Pomalidomide 4 mg orally daily on Days 1 to 21 and dexamethasone 40 mg on Days 1, 8, 15 and 22 of each 28-day cycle. Patients are to be treated until confirmed progression, unacceptable toxicity or the patient or investigator decides it is not in the patients best interest to continue.

Detailed Eligibility
INCLUSION CRITERIA:
1. Ages 18 years old or older
2. A prior diagnosis of multiple myeloma with documented disease progression requiring further treatment at time of screening
3. Measurable disease defined as any of the following:
- Serum monoclonal protein ≥ 0.5 g/dL by protein electrophoresis.
- >= 200 mg/24 hours of monoclonal protein in the urine on 24-hour electrophoresis
- Serum free light chain >= 10 mg/dL AND abnormal serum kappa to lambda free light chain ratio
4. Received 2-4 prior lines of therapy, including lenalidomide and a PI, either sequential or in the same line, and is refractory (relapsed and refractory or refractory) to lenalidomide in the last line. 5. Refractory status to lenalidomide is defined as progression while on lenalidomide therapy or within 60 days of last dose, following at least 2 cycles of lenalidomide with at least 14 doses of lenalidomide per cycle.
6. Life expectancy of ≥ 6 months
7. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
8. Females of child bearing potential (FCBP) must have a negative serum or urine pregnancy test prior to start of treatment. Participants must agree to ongoing pregnancy testing. All patients must be willing to comply with all requirements of the USA pomalidomide Risk Evaluation and Mitigation Strategy (REMS) program or the pomalidomide Pregnancy Prevention Plan (PPP).
9. Ability to understand the purpose and risks of the study and provide signed and dated informed consent.
10. 12-lead Electrocardiogram (ECG) with QT interval calculated by Fridericia Formula (QTcF) interval of ≤ 470 msec Fridericia Formula.
11. The following laboratory results must be met during screening and also immediately before study drug administration on Cycle 1 Day 1:
- Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3 (1.0 x 109/L)
- Platelet count ≥ 75,000 cells/mm3 (75 x 109/L)
- Hemoglobin ≥ 8.0 g/dl
- Total Bilirubin ≤ 1.5 x upper limit of normal (ULN), or patients diagnosed with Gilberts syndrome, that have been reviewed and approved by the medical monitor.
- Aspartate transaminase (AST /SGOT) and alanine transaminase (ALT/SGPT) ≤ 3.0 x ULN.
- Renal function: Estimated creatinine clearance by Cockcroft-Gault formula ≥ 45 mL/min.
12. Must be able to take antithrombotic prophylaxis.
13. Must have, or be willing to have an acceptable central catheter. (Port a cath, peripherally inserted central catheter [PICC-line], or central venous catheter) (Insertion only required if randomized to Arm A).

EXCLUSION CRITERIA:
1. Primary refractory disease (i.e. never responded (≥ MR) to any prior therapy)
2. Evidence of mucosal or internal bleeding or platelet transfusion refractory
3. Any medical conditions that, in the Investigator's opinion, would impose excessive risk to the patient or would adversely affect his/her participating in this study.
4. Prior exposure to pomalidomide
5. Known intolerance to IMiDs.
6. Known active infection requiring parenteral or oral anti-infective treatment within 14 days of randomization.
7. Other malignancy diagnosed or requiring treatment within the past 3 years with the exception of adequately treated basal cell carcinoma, squamous cell skin cancer, carcinoma in-situ of the cervix or breast or very low and low risk prostate cancer in active surveillance.
8. Pregnant or breast-feeding females
9. Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse compliance or follow-up evaluation
10. Known human immunodeficiency virus or active hepatitis C viral infection

** Contact study team for complete eligibility details

Applicable Disease Sites
Multiple Myeloma

Participating Institutions
UF Gainesville : Diane Richardson

Contact
Diane Richardson
Phone: +1 352-273-6844

Email: drichardson@ufl.edu