A Phase II open-label (non-blinded), single-arm (same treatment for all participants) multicenter trial of MP0250 plus bortezomib+dexamethasone in patients with multiple myeloma whose disease did not respond to/has recurred after standard treatments
- Conditions
- Multiple myeloma (MM) is a relatively rare (114 000 new cases worldwide in 2012, i.e. 0.8% of total cancer cases [Cancer Research UK Incidence Statistics 2016]) blood cancer for which there is no cure. Treatment options rather mitigate symptoms and defer end-stage disease. MM cells have a tendency to clonally evolve which results in development of drug resistance, and patients eventually relapse.Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-002771-10-CZ
- Lead Sponsor
- Molecular Partners AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 54
Participants are eligible to be included in the study only if all of the following criteria apply:
Type of Participant and Disease Characteristics
1. Patients with MM who have received:
Part 1 (Completed)
? =2 lines of therapy (including bortezomib and an IMiD), and
? Have shown no response (i.e. stable disease) to, or
? Have progressed in the most recent treatment, or
? Have progressed within 60 days of the most recent therapy.
Part 2
? =2 lines of prior therapy that included a proteasome inhibitor (bortezomib, carfilzomib or both) and an IMiD (thalidomide, lenalidomide and/or pomalidomide) either alone or in combination and,
? a response no better than SD lasting at least 4 months on a bortezomib- or carfilzomib-based, regimen as last line of therapy or,
? progression on treatment or within 60 days of stopping a bortezomib- or carfilzomib-based regimen as last line of therapy.
Note: For transplant-eligible patients enrolled to Part 1 or Part 2, induction plus conditioning chemotherapy/ASCT +/- maintenance therapy constitute one regimen.
2. Presence of a measurable disease with at least one of the following criteria:
? Serum M protein =0.5 g/dL, or
? Urine M protein =200 mg/24 h, or
? Involved serum free light chain (FLC) levels >100 mg/L and abnormal kappa/lambda (?/?) ratio in patients without detectable serum or urine M protein, or
? For patients with immunoglobulin A (IgA) myeloma whose disease can only be reliably measured by quantitative immunoglobulin measurement, a serum IgA level =0.5g/dL.
3. Eastern Cooperative Oncology Group (ECOG) performance status (0 to 1)
4. Life expectancy >3 months
5. Adequate hepatic function at Screening, with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <3x ULN and total bilirubin <2 x upper limit of normal (ULN). For patients with Gilbert’s syndrome (Gilbert-Meulengracht syndrome), higher bilirubin of 5 x ULN is acceptable
6. Absolute neutrophil count (ANC) =1000/mm3 at Screening. Screening ANC must be independent of growth factor support for =1 week
7. Hemoglobin =8.0 g/dL at Screening. Use of erythropoietic stimulating factors and red blood cell (RBC) transfusions per institutional guidelines is allowed, however most recent RBC transfusion must not have been done within 7 days prior to obtaining screening hemoglobin
8. Platelet count =50 000/mm3 at Screening. Patients must not have received platelet transfusions for at least 1 week prior to obtaining the screening platelet count
9. Measured or calculated creatinine clearance (CrCl) of = 45 mL/min at Screening based on the Cockcroft and Gault formula:
(140 - Age) x Mass (kg) / (72 x Creatinine mg/dL); multiply result by 0.85 if female
10. Serum albumin concentration = 25 g/L Note: Patients with lower levels of serum albumin at baseline may receive albumin supplementation to comply with this criterion.
Sex
11. Males and females =18 years of age
NOTE: The reliability of sexual abstinence for male and/or female enrollment eligibility needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the participant. Periodic abstinence (for example, calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
12. Male Participants: A male participant must agree to use a highly effective contraception from the Screening visit, during the treatment period and for at least 3 months after the last dose of study treatment and
Patients are excluded from the study if any of the following criteria apply:
Medical Conditions
1. Patients with the following diseases:
? Monoclonal gammopathy of undetermined significance (MGUS) of non-immunoglobulin (Ig)M and IgM subtypes
? Light chain MGUS
? Solitary plasmacytoma (alone or with minimal marrow involvement)
? Systemic Ig light chain amyloidosis
? Waldenstrom's Macroglobulinemia
? Myelodysplastic syndrome
? Plasma cell leukemia defined as a plasma cell count >2000/mm3
? Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS) syndrome
2. Peripheral neuropathy Grade 2 or higher at Screening or patients with a history of Grade 3/4 neuropathy or Grade 2 with pain
3. Prior or concurrent malignancy, except for:
? Adequately treated basal cell or squamous cell skin cancer, carcinoma in-situ of the cervix or breast or very low and low risk prostate cancer in active surveillance
? Or any other cancer from which the patient has been disease-free for >5 years
4. Active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic cardiac ischemia, or conduction abnormalities uncontrolled by conventional intervention. Myocardial infarction within 6 months prior to screening
5. Uncontrolled, hypertension (defined as systolic blood pressure (SBP) >150 mm Hg, diastolic blood pressure (DBP) >100 mm Hg despite antihypertensive medication)
6. Stroke, or transient ischemic attack within 6 months of Screening, clinically significant bleeding and vascular disease
7. Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
8. Significant concurrent, uncontrolled medical condition including, but not limited to, severe wound healing complication, renal (except related to MM), hepatic, hematological except MM, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease
9. Acute active infection requiring systemic antibiotics, antiviral (except antiviral therapy directed at hepatitis B) or antifungal agents within 14 days prior to screening
10. Clinical signs of or documented leptomeningeal or cerebral involvement of MM
Prior/Concomitant Therapy
11. Treatment with ixazomib as last line of therapy in Part 2
12. Therapy with approved or investigational anticancer therapeutics within 21 days (or in the case of nitrosureas, within 6 weeks) prior to treatment (except anti-myeloma treatment with a carfilzomib- or bortezomib-based regimen in Part 2) Note: Patients must have recovered from pre-existing, treatment-related adverse events to Grade 1 or lower
13. Autologous stem cell transplantation (ASCT) within 12 weeks before the date of enrollment
14. Prior allogeneic stem cell transplantation with active graft-versus-host-disease
15. Major surgery within 21 days prior to Screening
16. Immunotherapy within 21 days prior to Screening
17. Newly initiated therapy with bisphosphonate or RANKL (within two months prior to Screening). Patients on stable regimen with bisphosphonate or receptor activator of nuclear kappa-B ligand (RANKL)-inhibitor therapy over 2 months can continue these treatments at the same dose. No new therapy with bisphosphonate/RANKL inhibitor is allowed during the study
18. Radiation therapy within 2 months of Cycle 1, Day 1 is not permitted Except for local low-dose, palliative radiation to bone lesions for pain control.
Prior/Concurrent Clinical Study Experience
19. Patients who have received treatment w
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