A study comparing treatment with Melflufen in combination with Daratumumab and daratumumab treatment only in patients with Relapsed or Relapsed-Refractory Multiple Myeloma
- Conditions
- Patients with relapsed or relapsed-refractory multiple myeloma.MedDRA version: 16.1Level: HLTClassification code 10028229Term: Multiple myelomasSystem Organ Class: 100000004851Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-002161-36-FI
- Lead Sponsor
- Oncopeptides AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 240
1. Male or female, age 18 years or older;
2. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol;
3. A prior diagnosis of multiple myeloma with documented disease progression in need of treatment at time of screening;
4. Double refractory to an IMiD and a PI (regardless of the number of prior lines of therapy), or have received at least 3 prior lines of therapy including an IMiD and a PI (the definition of refractory includes intolerance to an IMiD/PI after at least two 28-day cycles of therapy);
5. Prior treatment with daratumumab or another anti-CD38 antibody is allowed if the patient has:
• Achieved at least PR and is not refractory to previous anti-CD38 antibody treatment
• At least 6 months since last dose of anti-CD38 antibody prior to Cycle 1/Day 1 (C1/D1)
• Not discontinued anti-CD38 antibody treatment due to related Grade = 3 toxicity
6. 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 24-hour urine collection by electrophoresis (UPEP)
• Serum free light chain (SFLC) = 10 mg/dL AND abnormal serum kappa to lambda free light chain (FLC) ratio
7. Life expectancy of = 6 months;
8. 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);
9. Ability to understand the purpose and risks of the study, ability to participate in all the procedures required by the protocol and provide signed and dated informed consent;
10. 12-lead Electrocardiogram (ECG) with QT interval calculated by Fridericia Formula (Q-TcF) interval of = 470 msec;
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 (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 transaminase/Aspartate aminotransferase (AST, also known as Serum Glutamic Oxaloacetic Transaminase (SGOT)) and Alanine transaminase/Alanine aminotransferase (ALT, also known as Serum Glutamic Pyruvic Transaminase (SGPT)) = 3.0 x ULN
• Renal function: Estimated creatinine clearance by Cockcroft- Gault formula of = 45 mL/min
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);
13. a) Male patients: Male patient who agrees to use contraception during the treatment period and for at least 3 months after the last dose of study treatment and refrain 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:
iii. Not a woman of childbearing potential (WOCBP)
or
iv. A WOCBP who agrees to fol
1. Primary refractory disease (i.e. never responded with at least MR to any prior therapy);
2. Prior treatment with CD38 CAR-T cell therapy or CD38/CD3 bispecific antibodies;
3. Chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume in 1 second (FEV1) less than 50% of predicted normal;
4. Moderate or severe persistent asthma within the past 2 years, or currently has uncontrolled asthma of any classification;
5. 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);
6. 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., heart failure class III or IV according to New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, significant cardiac conduction system abnormalities, uncontrolled hypertension, = Grade 3 thromboembolic event in the last 6 months);
7. Known active infection that is uncontrolled (including symptomatic or asymptomatic COVID-19) or has required intravenous systemic therapy within 14 days of randomization. Patients who has required oral antiinfective treatment within 14 days of randomization should be discussed with the Medical Monitor;
8. 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;
9. Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse compliance or follow-up evaluation;
10. Human immunodeficiency virus (HIV) or active hepatitis C viral infection, either known or if detected during screening;
11. Hepatitis B: both active (defined as HBsAg+) or non-active hepatitis B (defined as HBsAg-, Anti-HBs+, Anti-HBc+):
• Patients with prior hepatitis B vaccine are permitted (defined as HBsAg-, Anti-HBs+, Anti-HBc-).
12. Concurrent known or suspected amyloidosis or plasma cell leukemia;
13. POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes);
14. Known CNS or meningeal involvement of myeloma;
15. Any of the following treatments, within the specified timeframe:
• 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 mAb 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;
16. 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);
17. Prior stem cell transplant (autologous and/or allogenic) within 6 months of initiation of therapy;
18. Prior allogeneic stem cell transplantation with active graft-ve
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method