| Eligibility |
Inclusion Criteria:
- 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 more or equal to 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 less or equal than 10g dL
- Platelet count less than 100 109 L
- Prior treatment for WM comprising at least one regimen containing a therapeutic anti
CD20 monoclonal antibody rituximab administered for more or equal than 2 doses of
antibody treatment and or a therapeutic chemotherapy, alkylating agent, purine
analogue, bendamustine administered for more or equal than 2 cycles of treatment
- Patients may be either relapsing progressing at least 6 months after the last
administration of first line or subsequent treatment or refractory progressing on or
within 6 months of first line or subsequent treatment
- Number of prior regimens per lines 1 to 3
- Life expectancy more than 3 months.
- ECOG less or equal than 2.
- Meet the following pretreatment laboratory criteria at the screening visit conducted
within 28 days of study enrollment:
- ASAT 2.5 times the upper limit of institutional laboratory normal value.
- ALAT 2.5 times the upper limit of institutional laboratory normal value.
- Total bilirubin 1.5 times the upper limit of institutional laboratory normal
value unless clearly related to the disease or Gilbert syndrome
- Calculated or measured creatinin 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 6 months after end of therapy.
- A highly effective method of birth control is defined as those which result in a low
failure rate 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 after
and must agree to advice a female partner to use a highly effective method of birth
control.
- Voluntary written informed consent before carrying out any study related procedure not
part of normal medical care, with the understanding that consent may be withdrawn by
the subject at any time without prejudice to future medical care.
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
- Preexisting hepatic enzyme elevation ASAT, ALAT
- 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
- Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb):
Patients with presence of HBcAb, but absence of HBsAg, are eligible if hepatitis B
virus (HBV) DNA is undetectable (< 20 IU). Patients with positive serology should be
referred to a hepatologist or gastroenterologist before start of treatment and should
be monitored and managed following local standards to prevent hepatitis reactivation.
Furthermore transaminases and HBV DNA quantification must be tested at weeks 4 and 8
after treatment start. Then transaminases must be tested at week 12 of treatment
start.
- Preexisting pulmonary disease
- Known history of drug induced pneumonitis
- On-going inflammatory bowel disease
- Women who are pregnant. Women who are breast-feeding and do not consent to discontinue
breast-feeding Women of childbearing age who are not willing to use effective
anti-conceptive methods for the duration of the study and 6 months after end of
therapy
- 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
- Vaccination with live vaccines within 28 days prior to study entry
- Hypersensitivity to the active substance or to any of the excipients listed on part
6.1 of GAZYVARO and ZYDELIG SmCP
- 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.
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