Patients with multiple myeloma with residual disease after treatment MedDRA version: 18.1 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: KEYTRUDA 50 mg polvo
Product Name: KEYTRUDA 50 mg polvo
Product Code: SCH900475
MK-3475
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Pembrolizumab
CAS Number: 1374853-91-4
Current Sponsor code: SCH 900475
MK-3475
Other descriptive name: Anti-PD-1 monoclonal antibody
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-
Sponsors
Fundación Pethema
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Age = 18 years. 2.Performance status (ECOG) = 2. 3.Patient is, in the Investigators opinion, willing and able to comply with the protocol requirements. 4.Patient has given voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care. 5.Patients previously diagnosed with MM according to the IMWG Criteria (Blood 2011) who are in good response (= VGPR) but with persistent residual disease after the end of any therapy administered for a limited duration of time either as 1st or 2nd line of therapy. Persistent disease is defined by either the presence of an M-Component by electrophoresis, positive immunofixation, abnormal FLC ratio or identification of pathological plasma cells by flow cytometry. 6.At least 2 months for any non-transplant therapy or 3 months after ASCT, must elapse from the last dose of the previous treatment before being eligible to be included in the trial. 7.Response must be confirmed to be stable between the end of the previous therapy and the initiation of the trial (see the time that must elapse in the previous criteria). Stable is defined as: -No change in response according to the IMWG Criteria between these determinations. -No evidence of increase or decrease (> 25%) in M-component, provided the variation is > 0.5 mg/dl. -No evidence of increase or decrease (> 25%) of the involved FLC, provided the ratio is abnormal and the absolute change is > 10 mg/dL. -No evidence of increase or decrease (> 50%) of the percentage of pathological plasma cells by flow cytometry in the bone marrow provided the variation is > 0.5%. -No positivization or negativization of the electrophoresis or IFE between these determinations. In case of doubt, another determination separated at least 1 month after the last one is required to confirm the stability of the response, and this must be discussed with the DMC, prior to be eligible. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1.Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or other antibody or drug specifically targeting T cell co-stimulation). 2.Known hypersensitivity to pembrolizumab or any of its excipients. 3.Non-adequate hematological or biochemical parameters as specified below: a.Hemoglobin 2.5 x the upper limit range. e.Alanine transaminase (ALT): > 2.5 x the upper limit range. f.Total bilirubin: > 2 x the upper limit range. g.Creatinine clearance: < 30 mL/min (measured or calculated with the Cockcroft and Gault formula). 4.Absence of recovery from any significant non-hematological toxicity derived from previous treatments. The presence of alopecia and NCI-CTCAE grade < 2 symptomatic peripheral neuropathy is allowed. 5.Pregnant or lactating women or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment. Female subjects of childbearing potential should have a negative urine or serum pregnancy prior to study registration and re-tested within 72 hours prior to receiving the first dose of study medication. 6.Men and women of reproductive potential who are not using effective contraceptive methods (double barrier method, intrauterine device, oral contraception). Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. 7.Previous history of any other malignancy in the last 5 years (except basal cell carcinoma, skin epithelioma or carcinoma in situ of any site). 8.More than 2 prior lines of therapy for Multiple Myeloma. 9.Previous allogeneic stem cell transplantation. 10.Other relevant diseases or adverse clinical conditions: a.Congestive heart failure or angina pectoris, myocardial infarction within 12 months before inclusion in the study. b.Uncontrolled arterial hypertension or cardiac arrhythmias (i.e. requiring a change in medication within the last 3 months or a hospital admission within the past 6 months). c.History of significant neurological or psychiatric disorders. d.Active infection. e.Significant non-neoplastic liver disease (e.g., cirrhosis, active chronic hepatitis). f.Uncontrolled endocrine diseases (e.g. diabetes mellitus, hypothyroidism or hyperthyroidism) (i.e. requiring relevant changes in medication within the last month, or hospital admission within the last 3 months). 11.Active autoimmune disease or a documented history of autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen?s syndrome will not be excluded from the trial. 12.Patient is known to be
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To evaluate the efficacy of MK-3475 administered as consolidation therapy in Multiple Myeloma (MM) patients with residual disease after a previous treatment administered as 1st or 2nd line of therapy in terms of upgrade of the response;Secondary Objective: - To assess the safety of MK-3475 in patients with MM with persistent residual disease as determined by the incidence of clinical and laboratory toxicities. - To analyze the efficacy of MK-3475 administered as consolidation therapy in MM patients with residual disease after a previous treatment, in terms of achievement of negative MRD. - To analyze pharmacodynamics changes associated with MK-3475 treatment due to PD1/PDL1 blockade in lymphocytes and correlate them with the response obtained.;Primary end point(s): Efficacy:Upgrade of the response obtained with a previous therapy (VGPR to =CR; CR to =sCR; sCR-MRD+ to immunophenotypic CR) after treatment with MK-3475 as consolidation therapy in MM patients with residual disease.;Timepoint(s) of evaluation of this end point: Since the visit of selection (evaluation disease before doses administration) until end of trial (after follow-up period). According to modified IMWG criteria. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety: -Clinical and laboratory toxicities and rate of discontinuation of MK-3475 monotherapy in patients with MM with persistent residual disease. Efficacy: -Incidence of achievement of immunophenotypic sCR (MRD-) with MK-3475 monotherapy administered as consolidation therapy in patients with MM with persistent residual disease. -Pharmacodynamic parameters: basal levels of PD1/PDL1, receptor occupancy and immune activation markers;Timepoint(s) of evaluation of this end point: Safety:During all the participation of the patient in the study Efficacy:Since the visit of selection (evaluation disease before doses administration) until end of trial (after follow-up period). | — |
Countries
Spain
Contacts
Public ContactFundación Pethema
Fundación Pethema
Outcome results
None listed