Status and phase
Conditions
Treatments
About
This is an open-label Phase 1/2a study which will enroll patients that have relapsed or relapsed-refractory multiple myeloma to combination regimens of melflufen with currently approved agents. Patients will receive either melflufen+dexamethasone+bortezomib or melflufen+dexamethasone+daratumumab.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Male or female, age 18 years or older
A prior diagnosis of multiple myeloma with documented disease progression in need of treatment at time of screening
One to four prior lines of therapy
Measurable disease defined as any of the following:
Life expectancy of ≥ 6 months
ECOG performance status ≤ 2. (Patients with lower performance status based solely on bone pain secondary to multiple myeloma may be eligible following consultation and approval of the medical monitor)
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
Ability to understand the purpose and risks of the study and provide signed and dated informed consent
12-lead Electrocardiogram (ECG) with QT interval calculated by Fridericia Formula (QTcF) interval of ≤ 470 msec
Adequate organ function with the following laboratory results during screening (within 21 days) and immediately before study drug administration on Cycle 1 Day 1:
Must have, or be willing to have an acceptable central catheter. (Port a cath, peripherally inserted central catheter [PICC] line, or central venous catheter)
Regimen A
Must be intolerant or refractory to a prior IMiD; refractory defined as failure to respond (MR or better) or progression while on therapy or within 60 days of last dose.
Regimen B
Must have had a prior IMiD and a proteasome inhibitor (PI); alone or in combination and must be refractory or intolerant to an IMiD, PI or both.
Exclusion criteria
Primary refractory disease (i.e. never responded with ≥ MR to any prior therapy)
Evidence of mucosal or internal bleeding and/or are platelet transfusion refractory (i.e. platelet count fails to increase by > 10,000 cells/mm3 after 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 conduction system abnormalities, uncontrolled hypertension, ≥ Grade 3 thromboembolic event in the last 6 months)
Known active infection requiring parenteral or oral anti-infective treatment within 14 days of initiation of therapy
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
Known human immunodeficiency virus or active hepatitis B or C viral infection
Concurrent symptomatic amyloidosis or plasma cell leukemia
POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes)
Previous cytotoxic therapies, including cytotoxic investigational agents, for multiple myeloma 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 (mAb) within 4 weeks of initiation of therapy Prednisone up to but no more than 10 mg orally once daily (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
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 peripheral stem cell transplant within 12 weeks 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 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
Prior treatment with melflufen
Regimen A
Refractory to a PI in the last line of therapy prior to enrollment in this trial; refractory defined as failure to respond (MR or better) or progression while on therapy or within 60 days of last dose
History of allergic reaction/hypersensitivity attributed to compounds containing boron, mannitol, polysorbate 80 or sodium citrate dihydrate
Regimen B
Prior exposure to an antiCD-38 mAb
Chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume in 1 second (FEV1) less than 50% of predicted normal
Moderate or severe persistent asthma within the past 2 years, or currently has uncontrolled asthma of any classification
≥ Grade 3 conduction system abnormalities unless patient has a pacemaker
Active hepatitis B (defined as HBsAg+) or those at risk for reactivation (HBsAg-, Anti- HBs+, Anti-HBc+)
Patients with prior hepatitis B vaccine are permitted (defined as HBsAg-, Anti-HBs+, Anti-HBc-)
Primary purpose
Allocation
Interventional model
Masking
56 participants in 2 patient groups
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Data sourced from clinicaltrials.gov
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