Waldenstrom’s Macroglobulinemia (MW)
Conditions
Interventions
Trade Name: Gazyvaro
Product Name: Obinutuzumab
Product Code: R05072759/F06-01
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Obinutuzumab
CAS Number: 949142-50-1
Curr
Sponsors
FILO
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patient information and written informed consent - Age 18 years or older - Confirmed CD20 positive WM, according to the recommendations of the 2nd Workshop on WM. - Presence of at least one criterion for initiation of therapy, according to the 2nd Workshop on WM. ?Recurrent fever, night sweats, weight loss, fatigue ?Hyperviscosity ?Lympadenopathy which is either symptomatic or bulky (=5cm in maximum diameter) ?Symptomatic hepatomegaly and/or splenomegaly ?Symptomatic organomegaly and/or organ or tissue infiltration ?Peripheral neuropathy due to WM ?Symptomatic cryoglobulinemia ?Cold agglutinin anemia ?Immune hemolytic anemia and/or thrombocytopenia ?Nephropathy related to WM ?Amyloidosis related to WM ?Hemoglobin =10g/dL ?Platelet count 3 months. - ECOG = 2. - Meet the following pre-treatment laboratory criteria at the screening visit conducted within 28 days of study enrolment: ?ASAT (SGOT): ? 2.5 times the upper limit of institutional laboratory normal value. ?ALAT (SGPT): ? 2.5 times the upper limit of institutional laboratory normal value. ?Total bilirubin: ?1.5x times the upper limit of institutional laboratory normal valueunless clearly related to the disease or Gilbert’s syndrome ?Calculated or measured creatinine clearance by MDRD: ?40 mL/minute. - Premenopausal fertile females must agree to use a highly effective method of birth control for the duration of the therapy up to 18 months after end of therapy. A highly effective method of birth control is defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomised partner. - Men must agree not to father a child for the duration of therapy and 6 months afterand must agree to advice a female partner to use a highly effective method of birth control. 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 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: - Prior treatment with phosphatidylinositol 3 kinase (PI3K) inhibitors including idelalisib or GA101; - History of anaphylactic reaction following exposure to humanized monoclonal antibodies. - Previous allogeneic transplantation - Treatment with any other investigational agent or participating in another trial within 30 days prior to entering this study - History of other malignancy or chemotherapy/radiotherapy for any neoplastic disease other than WM prior to the study.EXCEPTION : History of malignancy except basal cell carcinoma of the skin, in situ carcinoma of breast or cervix treated surgically with curative intent, or any malignancy that has been in CR for 5 years at minimum, or as deemed appropriate for inclusion in the trial as per approval by the investigator - Medical condition requiring the long-term (estimated to be more than one month) use of oral corticosteroids. - Patients with signs of bacterial, viral or fungal infection - CMV PCR or antigenemia testing positive - Known history of drug induced liver injury, chronic active hepatitis C (HCV), chronic active hepatitis B (HBV), alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, on-going extra-hepatic obstruction caused by cholelithiasis, cirrhosis of the liver or portal hypertension - HIV antibody positive - Positive HBV HBsAG (surface) or positive HBC (core) antibody Note: The both should be tested and both have to be negative to be eligible for inclusion - Known history of drug induced pneumonitis - On-going inflammatory bowel disease - Lactation/pregnancy - Concurrent severe diseases which exclude the administration of therapy: *Heart insufficiency NYHA grade III/IV, LVEF < 50% and or RF <30%, myocardial infarction within the past 6 months prior to study *Severe chronic obstructive lung disease with hypoxemia *Severe diabetes mellitus *Hypertension difficult to control *Cerebral dysfunction - Richter’s syndrome - Cardiac amyloidosis - Any of the following laboratory abnormalities, if not related to lymphoma: *Absolute neutrophils count <1.5 x 109/L if not result of a bone marrow infiltration *Platelet count <75 x 109/L if not result of a bone marrow infiltration. *Central Nervous System involvement by lymphoma - Serious medical or psychiatric illness likely to interfere with participation in this clinical study. - No consent for registration, storage and processing of the individual disease-characteristics and course as well as information of the family physician about study participation - Patient with mental deficiency preventing proper understanding of the requirements of treatment - Person major under law control.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: - To evaluate ORR (overall response rate) including CR (complete response), VGPR (very good partial response), PR (partial response) and MR (minor response) - To evaluate the duration of response (RD), time to treatment failure (TTF), time to next treatment (TNT), cause-specific survival and overall survival (OS) for all study patients - To evaluate the time to best response (TBR) - To evaluate best overall response (BOR) - To evaluate the safety of the combination of idelalisib + obinutuzumab - To evaluate the efficacy according to MYD88 and CXCR4 mutations ;Primary end point(s): The aim of this study is to compare the total progression free survival (PFS) of relapsed/refractory WM patients with ECOG between 0 and 2, after chemo-free treatment combination with obinutuzumab + idelalisib as compared to that of the usual therapy based on chemo free treatments with Rituximab;Timepoint(s) of evaluation of this end point: PFS will be calculated from the date of inclusion to the following events (progression date and the date of the death if it occurred earlier). In the absence of progression and death, PFS duration will be censored at the stopping date or the date of last follow-up;Main Objective: To evaluate in advanced WM whether the progression free survival (PFS) is improved by obinutuzumab + idelalisib. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - To evaluate ORR (overall response rate): CR (complete response)+ VGPR (very good partial response) + PR (partial response) +MR (minor response) - To evaluate the duration of response (RD), time to treatment failure (TTF), time to next treatment (TNT), cause-specific survival and overall survival (OS) for all study patients - To evaluate the time to best response - To evaluate best overall response - To evaluate the safety of the combination of idelalisib + obinutuzumab - To evaluate the efficacy according to MYD88 and CXCR4 mutations.;Timepoint(s) of evaluation of this end point: - First evaluation: four weeks after end of last cycle of Obinutuzumab - After 730 days of Idelalisib - At the end of the study - Toxicity evaluation during all the study | — |
Countries
France
Contacts
Public ContactDelphine NOLLET
FILO
Outcome results
None listed