Status:
TERMINATED
A PK, Safety and Tolerability Study of Peripheral and Central Infusion of Melflufen in RRMM Patients
Lead Sponsor:
Oncopeptides AB
Conditions:
RRMM
Eligibility:
All Genders
18+ years
Phase:
PHASE2
Brief Summary
This is a randomized, two-period, cross-over Phase 2 study, comparing PK, and assessing safety and tolerability and efficacy of peripheral and central intravenous administration of melflufen in patien...
Eligibility Criteria
Inclusion
- Male or female, age 18 years or older
- Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol;
- A prior diagnosis of multiple myeloma (MM) with documented disease progression in need of treatment at time of screening;
- Measurable disease defined as any of the following:
- Serum monoclonal protein ≥ 0.5 g/dL by serum protein electrophoresis (SPEP)
- ≥ 200 mg/24hr of monoclonal protein in the 24hour urine collection by electrophoresis (UPEP)
- Serum free light chain (SFLC) ≥ 10 mg/dL AND abnormal serum kappa to lambda free light chain (FLC) ratio
- Received at least 2 prior lines of therapy and is refractory to an immunomodulatory drug (IMiD) and a proteasome inhibitor (PI). The definition of refractory includes intolerance to an IMiD/PI after at least two 28-day cycles of therapy, see Appendix 10 and Appendix 8.
- Adequate peripheral arm veins for repeated intravenous infusions
- Life expectancy of ≥ 6 months;
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2, see Appendix 6. Patients with ECOG performance status \> 2 solely based on bone pain secondary to MM may be eligible following consultation and approval of medical monitor;
- 12-lead Electrocardiogram (ECG) with QT interval calculated by Fridericia Formula (QTcF) interval of ≤ 470 msec, see Appendix 11;
- Adequate organ function with the following laboratory results during screening (within 21 days) and immediately before study treatment 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 treatment)
- Platelet count ≥ 75,000 cells/ mm³ (75 x 10⁹/L) (without transfusions during the 10 days prior to initiation of therapy)
- Hemoglobin ≥ 8.0 g/dL (Red blood cell \[RBC\] transfusions are permitted)
- Total Bilirubin ≤ 1.5 x upper limit of normal (ULN), except patients diagnosed with Gilbert's syndrome that have been reviewed and approved by the Medical Monitor
- Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) serum glutamic-pyruvic transaminase (SGPT) ≤ 3.0 x ULN
- Renal function: Estimated glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula of ≥ 45 mL/min, see Appendix 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 \[CVC\]) and a PVC;
- a) Male patients: A male patient is eligible if he agrees to use contraception as detailed in Appendix 4 of this protocol during the treatment period and for at least 3 months after the last dose of study treatment and refrains from donating sperm during this period b) Female patients: A female patient is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: I. Not a woman of childbearing potential (WOCBP) as defined in Appendix 4 or II. A WOCBP who agrees to follow the contraceptive guidance in Appendix 4 during the treatment period and for at least 28 days after the last dose of study treatment
Exclusion
- Primary refractory disease (i.e. never responded with at least minimal response \[MR\] to any prior therapy);
- Evidence of mucosal and/or internal bleeding or platelet transfusion refractory (platelet count fails to increase by \> 10,000 cells/mm³ after a transfusion of an appropriate dose of platelets);
- 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 cardiac conduction system abnormalities, uncontrolled hypertension, ≥ Grade 3 thromboembolic event in the last 6 months);
- Known active infection that is uncontrolled or has required intravenous systemic therapy within 14 days of randomization. Patients that have required oral anti-infective treatment within 14 days of randomization should be discussed with the Medical Monitor;
- 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;
- Pregnant or breast-feeding females;
- Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse compliance or follow-up evaluation;
- Human immunodeficiency virus (HIV) or active hepatitis B or C viral infection;
- Concurrent known or suspected amyloidosis or plasma cell leukemia;
- POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes);
- Known central nervous system (CNS) or meningeal involvement of myeloma
- Any of the following treatments, within the specified timeframe
- 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 or corticosteroids within 2 weeks prior to initiation of therapy.
- Other investigational therapies and monoclonal antibodies within 4 weeks of initiation of 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 therapy.
- Other washout times may be considered following consultation with the medical monitor.
- Residual side effects to previous therapy \> Grade 1 prior to initiation of therapy (Alopecia any grade and/or neuropathy Grade 1 without pain are permitted);
- Prior stem cell transplant (autologous and/or allogenic) within 6 months of initiation of therapy;
- Prior allogeneic stem cell transplantation with active graft-versus-host-disease;
- Prior major surgical procedure or radiation therapy within 4 weeks of the initiation of therapy (this does not include limited course of radiation used for management of bone pain within 7 days of initiation of therapy);
- Known intolerance to the required dose and schedule of steroid therapy, as determined by the investigator;
- Known hypersensitivity reaction to melphalan, melflufen or its excipients
- Prior treatment with melflufen
Key Trial Info
Start Date :
August 4 2020
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
January 10 2022
Estimated Enrollment :
27 Patients enrolled
Trial Details
Trial ID
NCT04412707
Start Date
August 4 2020
End Date
January 10 2022
Last Update
March 9 2023
Active Locations (10)
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1
The Oncology Institute of Hope & Innovation - Glendale
Glendale, California, United States, 91204
2
Specialized Hospital for Active Treatment of Hematological Diseases, Sofia
Sofia, Bulgaria
3
Multiprofile Hospital for Active Treatment "Sveta Marina", Varna
Varna, Bulgaria
4
University Hospital Brno, Clinic of Internal Medicine - Hematology and Oncology
Brno, Czechia, 62500