A PK Study of Melphalan During Treatment With Melphalan Flufenamide (Melflufen) and Dex in RRMM Pat With Impaired Renal Function

• Status: Active, not recruiting
• Trial end date: 2022-09-30
• Target enrollment: 0
• Participant gender: All

Summary

This is a multicenter, PK study of Melphalan during treatment with Melflufen and Dexamethasone in patients with RRMM and impaired renal function. Received 2 - 4 prior lines of therapy and a renal function (creatinine clearance by Cockcroft-Gault formula) between ≥30 mL/min to <45 mL/min in Cohort 1,and ≥15 mL/min to <30 mL/min in Cohort 2.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Oncopeptides AB
• Treatments: BB 1101; Dexamethasone; Dexamethasone acetate; Melphalan

Criteria

Inclusion Criteria:

1. Male or female, age 18 years or older

2. A prior diagnosis of MM with documented disease progression

3. 2 - 4 prior lines of therapy

4. Measurable disease defined as any of the following:

• Serum monoclonal protein ≥ 0.5 g/dL by serum protein electrophoresis (SPEP).

• ≥ 200 mg/24 hours of monoclonal protein in the urine on 24-hour urine electrophoresis (UPEP)

• Serum free light chain (SFLC) ≥ 10 mg/dL AND abnormal serum kappa to lambda free light chain ratio

5. Life expectancy of ≥ 6 months

6. ECOG performance status ≤ 2. (Patients with lower performance status based solely on bone pain secondary to MM may be eligible following consultation and approval of the medical monitor)

7. Patient is a female of childbearing potential (FCBP)* with a negative serum or urine pregnancy test prior to initiation of therapy and agrees to practice appropriate methods of birth control, or the patient is male and agrees to practice appropriate methods of birth control

8. Ability to understand the purpose and risks of the study and provide signed and dated informed consent.

9. 12-lead Electrocardiogram (ECG) with QT interval calculated by Fridericia Formula (QTcF) interval of ≤ 470 msec

10. Renal function: Estimated eGFR by CKD-EPI formula between ≥30 mL/min to <45 mL/min at screening and at Cycle 1 Day 1 for cohort 1A and 1B, between ≥15 mL/min to < 30 mL/min for cohort 2A and 2B.

11. The following laboratory results must be met during screening and immediately before study drug administration on Cycle 1 Day 1:

• Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3 (1.0 x 109/L) (Growth factors cannot be used within 10 days [14 days for pegfilgrastim] prior to initiation of study therapy)

• Platelet count ≥ 75,000 cells/mm3 (75 x 109/L) (without transfusions during the 10 days prior to initiation of study therapy)

• Hemoglobin ≥ 8.0 g/dL (red blood cell [RBC] transfusions are permitted)

• Total Bilirubin ≤ 1.5 x upper limit of normal (ULN), or higher in patients diagnosed with Gilberts syndrome that have been reviewed and approved by the medical monitor.

• AST/SGOT and ALT/SGPT ≤ 3.0 x ULN.

12. Must have, or be willing to have, an acceptable central catheter. (Port a cath, peripherally inserted central catheter [PICC] line, or central venous catheter)

• (FCBP) is any sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal (not having menstrual cycles due to cancer therapy does not rule out childbearing potential) for at least 24 consecutive months.

Exclusion Criteria:

1. Primary refractory disease (i.e. never responded with ≥ MR to any prior therapy)

2. Evidence of mucosal or internal bleeding and/or platelet transfusion refractory (platelet count fails to increase by > 10,000 cells/mm3 [10.0 x 109/L] after a transfusion of an appropriate dose of platelets)

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. Examples of such conditions are: a significant history of cardiovascular disease (e.g., myocardial infarction, significant conduction system abnormalities, uncontrolled hypertension, ≥ Grade 3 thromboembolic event in the last 6 months),

4. Known active infection requiring parenteral or oral anti-infective treatment within 14 days of initiation of therapy.

5. 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.

6. Pregnant or breast-feeding females

7. Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse compliance or follow-up evaluation

8. Known human immunodeficiency virus or active hepatitis B or C viral infection

9. Concurrent symptomatic amyloidosis or plasma cell leukemia

10. POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes)

11. Previous cytotoxic therapies, including cytotoxic investigational agents, for MM within 3 weeks (6 weeks for nitrosoureas) prior to initiation of therapy. The use of live vaccines within 30 days before initiation of therapy. IMiDs, PIs and corticosteroids within 14 days prior to initiation of study therapy. Other investigational therapies and monoclonal antibodies within 4 weeks of initiation of study therapy. Prednisone up to but no more than 10 mg orally q.d. or its equivalent for symptom management of comorbid conditions is permitted but dose should be stable for at least 7 days prior to initiation of study therapy. Plasmapheresis is not permitted within 14 days of initiation of therapy.

12. Residual side effects to previous therapy > Grade 1 prior to enrollment (Alopecia any grade and/or neuropathy Grade 2 without pain are permitted)

13. Prior peripheral stem cell transplant within 12 weeks of initiation of study therapy

14. Prior allogeneic stem cell transplantation with active graft-versus-host-disease.

15. Prior major surgical procedure or radiation therapy within 4 weeks of the initiation of study therapy (this does not include limited course of radiation used for management of bone pain to be completed within 7 days of initiation of study therapy).

16. Known intolerance to steroid therapy

17. Prior renal transplant

18. Currently in need of renal dialysis