Relapsed or refractory Waldenström’s Macroglobulinemia.
Conditions
Interventions
Trade Name: Arzerra
Product Name: Ofatumumab
Product Code: GSK1841157
Pharmaceutical Form: Concentrate and solvent for concentrate for solution for infusion
INN or Proposed INN: OFATUMUMAB
CAS Number:
Sponsors
National and Kapodistrian University of Athens
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care. 2. Clinicopathological diagnosis of Waldenström’s macroglobulinemia (WM) as defined by “Consensus Panel One” of the Second International Workshop on Waldenström’s macroglobulinemia (Owen, Treon et al. 2003): • IgM monoclonal gammopathy of any concentration. • Bone marrow infiltration by small lymphocytes showing plasmacytoid/plasma cell differentiation. • Intertrabecular pattern of bone marrow infiltration. • Surface IgM+ CD5+ CD10- CD19+ CD20+ CD22+ CD23- CD25+ CD27+ FMC7+ CD103- CD138- immunophenotype*. *Variations from this immunophenotypic profile can occur. All patients with the diagnosis of Waldenstrom’s Macroglobulinemia will be evaluable for response according to the response criteria. 3. Patients must have at least one of the following indications to initiate treatment as defined by “Consensus Panel Two” recommendations from the Second International Workshop on Waldenstrom’s Macroglobulinemia (Kyle, Treon et al. 2003): • 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 5g/dL even with no symptoms. 4. Measurable disease as defined by a monoclonal IgM paraprotein level greater than 1000mg/dl. 5. At least one prior systemic treatment for WM, which should have been concluded at least 4 weeks prior to enrolment. Prior plasmapheresis to control hyperviscosity is not considered as a systemic therapy. 6. CD20 positive disease based on any previous bone marrow immunohistochemistry or flow cytometric analysis performed up to 3 months prior to enrollment. 7. Age > 18 years of age. 8. ECOG PS of ? 2 at study entry and a life expectancy of greater than 3 months. 9. Karnofsky performance status = 60. 10. Ability to adhere to study visit schedule and other protocol requirements. 11. Adequate organ function as defined by: • Absolute neutrophil count > 1000/µl unless the result of bone marrow infiltration by WM. • Platelet count > 50.000 /µl. • ALT and AST =65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
Exclusion criteria: 1. Screening liver tests: - total bilirubin >1.5 times upper normal limit (unless due to WM involvement of liver or a known history of Gilbert’s disease). - ALT >2.5 times upper normal limit (unless due to WM involvement of liver). - alkaline phosphatase >2.5 times upper normal limit (unless due to WM involvement of the liver). 2. Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active Hepatitis C. 3. Other past or current malignancy. Subjects who have been free of malignancy for at least 5 years, or have a history of completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma are eligible. 4. Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomization, congestive heart failure (NYHA III-IV), and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities. 5. Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which in the opinion of the investigator may represent a risk for the patient. 6. History of significant cerebrovascular disease or ongoing event with active symptoms or sequelae. 7. Known HIV positive. 8. Previous treatment or known or suspected hypersensitivity to ofatumumab. 9. Any known contra-indication to any drug of the chemotherapy regimen. 10. Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment). 11. Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test will be performed and if positive the subject will be excluded. 12. Positive serology for hepatitis C (HC) defined as a positive test for HCAb, in which case reflexively perform a HC RIBA immunoblot assay on the same sample to confirm the result. 13. Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half-lives or 4 weeks prior to enrollment, whichever is longer, or currently participating in any other interventional clinical study. 14. Known or suspected inability to comply with a study protocol. 15. Pregnant or lactating women. Women of childbearing potential must have a negative pregnancy test at screening. 16. Women of childbearing potential, including women whose last menstrual period was less than one year prior to screening, unable or unwilling to use adequate contraception from study start to one year after the last dose of protocol therapy. Adequate contraception is defined as hormonal birth control, intrauterine device, double barrier method or total abstinence. 17. Male subjects unable or unwilling to use adequate contraception methods from study start to one year after the last dose of protocol therapy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Overall Response Rate (ORR) to the OFC combination regimen in patients with relapsed or refractory WM.;Secondary Objective: 1. To determine complete, partial and minor response rates for treatment with OFC in patients with relapsed or refractory WM. 2. To determine the safety and toxicity profile for treatment with OFC in patients with relapsed or refractory WM. 3. To determine overall survival (OS), progression-free survival (PFS), duration of response, and time to next treatment for treatment with OFC in patients with relapsed or refractory WM. 4. To determine the incidence and characteristics (if present), of an “IgM flare” for treatment with OFC in patients with relapsed or refractory WM.;Primary end point(s): To evaluate the overall response rate (ORR) from OFC (MR+PR+CR).;Timepoint(s) of evaluation of this end point: At the end of the clinical trial. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Calculating the proportion of patients having different levels of response (MR, PR and CR). • Increase of IgM = 25% ("IgM flare") after the initial infusion of OFC. • Overall Survival (OS), Progression Free Survival (PFS), duration of response and time until next therapy. • Relapse or progression after OFC. • Therapy after OFC. • Death due to any cause. • Death due to WM. • Safety and toxicity of OFC regimen.;Timepoint(s) of evaluation of this end point: At the end of the clinical trial. | — |
Countries
Greece
Contacts
Public ContactProf. Meletios-Athansios Dimopoulos
National and Kapodistrian University of Athens
Outcome results
None listed