- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03679455
A Study of Obinutuzumab (RO5072759) Induction in Patients With Relapsed/ Refractory Waldenström Macroglobulinemia, OBI-1 (OBI-1)
November 9, 2018 updated by: Polish Myeloma Consortium
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.
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).
Study Overview
Status
Unknown
Conditions
Intervention / Treatment
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)
Study Type
Interventional
Enrollment (Anticipated)
30
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Dominik Dytfeld, MD, PhD
- Phone Number: +48 602 464 708
- Email: dytfeld@me.com
Study Contact Backup
- Name: Tomasz Wróbel, MD, PhD
- Phone Number: +48 501 419 272
- Email: wrobeltw@gmail.com
Study Locations
-
-
Dolnośląskie
-
Wrocław, Dolnośląskie, Poland, 50-367
- Recruiting
- Uniwersytecki Szpital kliniczy im. Jana Mikulicza-Radeckiego we Wrocławiu; Klinika Hematologii, Nowotworów Krwi Transplantacji Szpiku
-
Contact:
- Tomasz Wróbel, MD, PhD
- Phone Number: +48 501 419 272
- Email: wrobeltw@gmail.com
-
Contact:
- Agnieszka Szeremet, MD
- Phone Number: +48 71 784 22 77
- Email: agnieszka.szeremet@wp.pl
-
Principal Investigator:
- Tomasz Wróbel, MD, PhD
-
Sub-Investigator:
- Agnieszka Szeremet, MD
-
Sub-Investigator:
- Elżbieta Kalicińska, MD
-
-
Wielkopolskie
-
Poznań, Wielkopolskie, Poland, 60-569
- Recruiting
- Szpital Kliniczny Przemienienia Pańskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu; Oddział Hematologii i Transplantacji Szpiku
-
Contact:
- Dominik Dytfeld, MD, PhD
- Phone Number: +48 602464708
- Email: dytfeld@me.com
-
Contact:
- Elżbieta Gwazdacz-Magiera
- Phone Number: +48 535818919
- Email: egm1@tlen.pl
-
Principal Investigator:
- Dominik Dytfeld, MD, PhD
-
Sub-Investigator:
- Adam Nowicki, MD
-
Sub-Investigator:
- Tomasz Szczepanik, MD
-
Sub-Investigator:
- Bartosz Małecki, MD
-
Sub-Investigator:
- Magdalena Matuszak, MD
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
- 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 ≤10 g/dL
- Platelet count <100 × 109/L
- Subjects must have received prior therapies for their WM and have relapsed or refractory WM requiring therapy. Any number of prior therapies is acceptable. Relapsed WM: defined as a subject who has received at least one prior WM therapy and previously achieved a complete or partial remission/response lasting at least 6 months Refractory WM: is defined as progression on treatment; disease progression < 6 months of the last anti-WM therapy
Subjects must have adequate organ and marrow function as defined below:
- Absolute neutrophil count ≥ 1.5 x 109/l (unless decreased due to WM involvement of the bone marrow)
- Platelets ≥ 75 x 109/l (unless decreased due to WM involvement of the bone marrow)
- Hemoglobin ≥ 9 g/dL
- Total bilirubin ≤ 1.5 x ULN or < 2 x ULN if attributable to hepatic infiltration by neoplastic disease
- AST and ALT < 2.5 x ULN
- Calculated creatinine clearance by Cockcroft-Gault formula >40 mL/min
- INR ≤ 1.5
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
- 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 < 1) such as oral contraceptives, intrauterine device, sexual abstinence or barrier method of contraception in conjunction with spermicidal jelly, during study treatment and for 18 months after end of obinutuzumab treatment.
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.
- Concurrent use of other anti-cancer agents or treatments.
- Prior use of any investigational monoclonal antibody therapy within 6 months of study start.
- History of severe allergic or anaphylactic reactions to monoclonal antibody therapy, known hypersensitivity to any of the study drugs or sensitivity to murine products.
- 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.
- Prior use of radiation therapy within 4 weeks of enrollment.
- 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.
- History of illicit drug or alcohol abuse within 12 months prior to screening, in the investigator's judgment.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment arm
Obinutuzumab (RO5072759) 25 MG/ML; Obinutuzumab will be administered by iv.
infusion as an absolute (flat) dose of 1000 mg.
|
Study treatment, obinutuzumab is a Type II humanized anti-CD20 monoclonal antibody of the IgG1 subclass derived by humanization of the parental B-Ly1 mouse antibody and produced in the Chinese Hamster Ovary cell line by recombinant DNA technology.
The Study Treatment, obinutuzumab is a liquid concentrate for infusion.
Obinutuzumab vials are type 1 glass vials with a butyl rubber stopper.
Obinutuzumab is provided as a single 1000 mg dose liquid concentrate with a strength of 25 mg/mL.
It is supplied in 50 mL glass vials containing 40 mL of the 25 mg/mL liquid concentrate.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Up to 3,5 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression Free Survival (PFS)
Time Frame: Up to 3,5 years
|
PFS will be calculated as time from fist treatment dose until progression or death of any cause.
The PFS will be defined as well-documented and verifiable data.
The Kaplan-Meier curve will be provided.
The median time to PFS along with associated 95% confidence interval will be provided as well.
|
Up to 3,5 years
|
Overall Survival (OS)
Time Frame: from first study treatment dose till 1 year after the treatment period
|
OS is defined as time from first study treatment dose to death due to any cause.
Survival distributions will be estimated using the Kaplan-Meier method.
Each subject will be followed for 1 year after the treatment period.
|
from first study treatment dose till 1 year after the treatment period
|
Overall Response Rate (ORR)
Time Frame: after 6 Cycles of obinutuzumab treatment (after induction phase); each cycle is 21 days in Induction Phase;
|
ORR as a secondary endpoint will be assessed after completion of induction phase and after maintenance phase.
Responders include subjects with at least MR (CR, VGPR, PR, MR).
Non-responders include subjects with Stable Disease (SD) and Progressive Disease (PD).
Subjects with unknown or missing responses will be considered as non-responders.
|
after 6 Cycles of obinutuzumab treatment (after induction phase); each cycle is 21 days in Induction Phase;
|
Overall Response Rate (ORR)
Time Frame: 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;
|
ORR as a secondary endpoint will be assessed after completion of induction phase and after maintenance phase.
Responders include subjects with at least MR (CR, VGPR, PR, MR).
Non-responders include subjects with Stable Disease (SD) and Progressive Disease (PD).
Subjects with unknown or missing responses will be considered as non-responders.
|
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;
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Tomasz Wróbel, MD.PhD, USK Wrocław
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
September 21, 2018
Primary Completion (Anticipated)
April 1, 2019
Study Completion (Anticipated)
December 1, 2022
Study Registration Dates
First Submitted
June 4, 2018
First Submitted That Met QC Criteria
September 19, 2018
First Posted (Actual)
September 20, 2018
Study Record Updates
Last Update Posted (Actual)
November 13, 2018
Last Update Submitted That Met QC Criteria
November 9, 2018
Last Verified
November 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Neoplasms, Plasma Cell
- Waldenstrom Macroglobulinemia
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Obinutuzumab
Other Study ID Numbers
- ML39235
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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