Waldenström's macroglobulinemia MedDRA version: 20.1 Level: HLT Classification code 10047802 Term: Waldenstrom's macroglobulinaemias System Organ Class: 100000004851
Conditions
Interventions
Trade Name: Gazyvaro
Product Name: Obituzumab
Product Code: GA-101
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Obinutuzumab
CAS Number: 949142-50-1
Current Sponsor
Sponsors
Polish Myeloma Consortium
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed written informed consent prior to beginning study-related procedures. 2. Male and female subjects aged = 18 years. 3. Able to comply with the study protocol, in the investigator’s judgment. 4. Confirmed clinicopathological diagnosis of WM with detectable CD20 positive of the tumor cells 5. Measurable disease defined as serum monoclonal IgM >0.5 g/dL 6. Active disease and indication for treatment based on the Seventh IWWM recommendations (Dimopoulos et al., 2014) defined by presence of at least any one of the following conditions: - Recurrent fever, night sweats, weight loss, fatigue - Hyperviscosity - Lymphadenopathy which is either symptomatic or bulky (=5 cm in maximum diameter) - Symptomatic hepatomegaly and/or splenomegaly - Symptomatic organomegaly and/or organ or tissue infiltration - Peripheral neuropathy due to WM - Symptomatic cryglobulinemia - Cold agglutinin anemia - Immune hemolytic anemia and/or thrombocytopenia - Nephropathy related to WM - Amyloidosis related to WM - Hemoglobin =10 g/dL - Platelet count 40 mL/min - INR = 1.5 9. Eastern Cooperative Oncology Group (ECOG) performance status of = 2. 10. Fertile men or women of childbearing potential, unless = 2 years after the onset of menopause (for women), must be willing to use a highly effective contraceptive method (Pearl Index =65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 1. Lactating women, women with a positive pregnancy test at Visit 1 or women (of childbearing potential) as well as men with partners of childbearing potential, who are not willing to use adequate contraception from study start through 18 months after end of obinutuzumab treatment. 2. Known involvement of the central nervous system by WM. 3. Vaccination with a live vaccine a minimum of 28 days prior to study enrolment (vaccination day considered as Day 0). 4. History of stroke or intracranial hemorrhage within 12 months prior to study enrollment. 5. Currently active, clinically significant cardiovascular disease. 6. Any active systemic infection. Caution should be exercised when considering the use of obinutuzumab in patients with a history of recurring or chronic infections. 7. Positive for hepatitis C antibody at screening. 8. Positive test result for chronic hepatitis B virus (HBV) infection (defined as a positive HBsAg serology). Patients with occult or prior HBV infection (defined as negative hepatitis B surface antigen [HBsAg] and positive total hepatitis B core antibody [HBcAb]) may be included if HBV DNA is undetectable, provided that they are willing to undergo monthly DNA testing during treatment and follow-up until 12 months after the last dose of obinutuzumab. 9. Known HIV infection at screening. 10. Any serious illness, medical condition, organ system dysfunction or abnormality in clinical laboratory test that, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk. 11. Concurrent use of other anti-cancer agents or treatments. 12. Prior use of any investigational monoclonal antibody therapy within 6 months of study start. 13. History of severe allergic or anaphylactic reactions to monoclonal antibody therapy, known hypersensitivity to any of the study drugs or sensitivity to murine products. 14. Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half-lives or 4 Weeks prior to first study treatment dose, whichever is longer, or participation in any other interventional clinical study. 15. Prior use of radiation therapy within 4 weeks of enrollment. 16. History of other malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer. 17. History of illicit drug or alcohol abuse within 12 months prior to screening, in the investigator’s judgment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective of this study is to evaluate Best Overall Response (BOR).;Secondary Objective: 1. To evaluate the efficacy of obinutuzumab based on investigator assessed overall response rate (ORR). 2. To evaluate progression-free survival (PFS). 3. To evaluate overall survival (OS). 4. To evaluate disease and prognostic marker correlation with clinical response.;Primary end point(s): BOR is the best response recorded from the start of the study treatment until the disease progression. As a responder is considered patient with at least MR (CR, VGPR, PR, MR). BOR will be presented as rates with corresponding exact 95% CI.;Timepoint(s) of evaluation of this end point: Response to treatment will be assessed after induction phase and every 24 weeks during maintenance phase, and after completion of maintenance. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Overall response rate (ORR) as determined by Investigator evaluation, is the percentage of subjects achieving an objective response using the response criteria for patients with Waldenström's Macroglobulinemia updated at the VI International Workshop on WM, calculated at the following time-points: - after 6 Cycles of obinutuzumab treatment (after induction phase) before study treatment administration at the C1M, - after all 12 Cycles of treatment (at first visit in follow-up phase – FU2M) or after the last dose, if not after 12 Cycles of obinutuzumab. 2. PFS defined as time from first study treatment dose until progression or death of any cause. 3. OS defined as time from first study treatment dose to death due to any cause. 4. - Change in IgG, IgA, IgM quantities, - Improvement of ECOG, - Improvement in constitutional symptoms, - ß2-Microglobulin.;Timepoint(s) of evaluation of this end point: - after 6 Cycles of obinutuzumab treatment (after induction phase) before study treatment administration at the C1M - before study treatment administration at every third maintenance phase cycle (C3M, C6M, C9M, C12M) of obinutuzumab (response evaluations to occur before study treatment administration at the start of cycles) - after all 12 Cycles of treatment (at first visit in follow-up phase FU2M) or after the last dose, if not after 12 Cycles of obinutuzumab. | — |
Countries
Poland
Contacts
Public ContactPolish Myeloma Consortium
Polish Myeloma Consortium
Outcome results
None listed