A Multicenter, Single-arm, Phase II Study to Evaluate a Safety and Efficacy of Obinutuzumab Induction Followed by 2 Years of Maintenance in Patients With Relapsed/Refractory Waldenström Macroglobulinemia.

Polish Myeloma Consortium2 sites in 1 country30 target enrollmentSeptember 21, 2018

ConditionsWaldenstrom Macroglobulinemia

InterventionsObinutuzumab 25 MG/ML

DrugsObinutuzumab 25 MG/ML

Overview

Phase: Phase 2
Intervention: Obinutuzumab 25 MG/ML
Conditions: Waldenstrom Macroglobulinemia
Sponsor: Polish Myeloma Consortium
Enrollment: 30
Locations: 2
Primary Endpoint: Best Overall Response (BOR)
Last Updated: 7 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a multi-center, single-arm, open label, non-randomized, phase II study designed to investigate the efficacy, safety and tolerability of obinutuzumab given as monotherapy in patients with relapsed/refractory Waldenström Macroglobulinemia (R/R MW).

Detailed Description

Study to investigate the efficacy, safety and tolerability of obinutuzumab administered as monotherapy in patients with relapsed/refractory Waldenström Macroglobulinemia (R/R WM)

Registry

clinicaltrials.gov

Start Date

September 21, 2018

End Date

December 2022

Last Updated

7 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Polish Myeloma Consortium

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Signed written informed consent prior to beginning study-related procedures.
•Male and female subjects aged ≥ 18 years.
•Able to comply with the study protocol, in the investigator's judgment.
•Confirmed clinicopathological diagnosis of WM with detectable CD20 positive of the tumor cells
•Measurable disease defined as serum monoclonal IgM \>0.5 g/dL
•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

Exclusion Criteria

•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.
•Known involvement of the central nervous system by WM.
•Vaccination with a live vaccine a minimum of 28 days prior to study enrolment (vaccination day considered as Day 0).
•History of stroke or intracranial hemorrhage within 12 months prior to study enrollment.
•Currently active, clinically significant cardiovascular disease.
•Any active systemic infection. Caution should be exercised when considering the use of obinutuzumab in patients with a history of recurring or chronic infections.
•Positive for hepatitis C antibody at screening.
•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.
•Known HIV infection at screening.
•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.

Arms & Interventions

Treatment arm

Obinutuzumab (RO5072759) 25 MG/ML; Obinutuzumab will be administered by iv. infusion as an absolute (flat) dose of 1000 mg.

Intervention: Obinutuzumab 25 MG/ML

Outcomes

Primary Outcomes

Best Overall Response (BOR)

Time Frame: Up to 3,5 years

BOR is the best response recorded from the start of the treatment until disease progression: response assessments recorded as CR, VGPR, PR, MR, SD, PD. 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.

Secondary Outcomes

Progression Free Survival (PFS)(Up to 3,5 years)
Overall Survival (OS)(from first study treatment dose till 1 year after the treatment period)
Overall Response Rate (ORR)(after all 12 Cycles of treatment in Maintenance Phase (at first visit in follow-up phase FU2M) or after the last dose, if not after 12 Cycles of obinutuzumab (each cycle is 8 weeks in Maintenance Phase;)