Clinical trial in exploration phase, to suministrate monoclonal antibody anti-PD1 Pembrolizumab (MK-3475)as consolidation therapy in patients with multiple myeloma with residual disease after treatment.
- Conditions
- Patients with multiple myeloma with residual disease after treatmentMedDRA version: 18.1Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-003359-23-ES
- Lead Sponsor
- Fundación Pethema
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 20
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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.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
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 < 8.0 g/dl.
b.Platelets count < 75 x109/L without previous platelet transfusions in the last 7 days.
c.Neutrophils (ANC) <1 × 109/L without growth factor support (defined as no growth factor administration for at least 14 days prior to observation).
d.Aspartate transaminase (AST): > 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
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