A Study of Obinutuzumab (RO5072759) Induction in Patients With Relapsed/ Refractory Waldenström Macroglobulinemia, OBI-1 (OBI-1)
Primary Purpose
Waldenstrom Macroglobulinemia
Status
Unknown status
Phase
Phase 2
Locations
Poland
Study Type
Interventional
Intervention
Obinutuzumab 25 MG/ML
Sponsored by
About this trial
This is an interventional treatment trial for Waldenstrom Macroglobulinemia
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
- 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.
Sites / Locations
- Uniwersytecki Szpital kliniczy im. Jana Mikulicza-Radeckiego we Wrocławiu; Klinika Hematologii, Nowotworów Krwi Transplantacji SzpikuRecruiting
- Szpital Kliniczny Przemienienia Pańskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu; Oddział Hematologii i Transplantacji SzpikuRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment arm
Arm Description
Obinutuzumab (RO5072759) 25 MG/ML; Obinutuzumab will be administered by iv. infusion as an absolute (flat) dose of 1000 mg.
Outcomes
Primary Outcome Measures
Best Overall Response (BOR)
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 Outcome Measures
Progression Free Survival (PFS)
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.
Overall Survival (OS)
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.
Overall Response Rate (ORR)
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.
Overall Response Rate (ORR)
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.
Full Information
NCT ID
NCT03679455
First Posted
June 4, 2018
Last Updated
November 9, 2018
Sponsor
Polish Myeloma Consortium
Collaborators
Roche Pharma AG, Bioscience, S.A.
1. Study Identification
Unique Protocol Identification Number
NCT03679455
Brief Title
A Study of Obinutuzumab (RO5072759) Induction in Patients With Relapsed/ Refractory Waldenström Macroglobulinemia, OBI-1
Acronym
OBI-1
Official Title
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.
Study Type
Interventional
2. Study Status
Record Verification Date
November 2018
Overall Recruitment Status
Unknown status
Study Start Date
September 21, 2018 (Actual)
Primary Completion Date
April 2019 (Anticipated)
Study Completion Date
December 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Polish Myeloma Consortium
Collaborators
Roche Pharma AG, Bioscience, S.A.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Waldenstrom Macroglobulinemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
multi-center, single-arm, open label, non-randomized
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment arm
Arm Type
Experimental
Arm Description
Obinutuzumab (RO5072759) 25 MG/ML; Obinutuzumab will be administered by iv. infusion as an absolute (flat) dose of 1000 mg.
Intervention Type
Drug
Intervention Name(s)
Obinutuzumab 25 MG/ML
Other Intervention Name(s)
Gazyvaro
Intervention Description
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.
Primary Outcome Measure Information:
Title
Best Overall Response (BOR)
Description
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.
Time Frame
Up to 3,5 years
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
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.
Time Frame
Up to 3,5 years
Title
Overall Survival (OS)
Description
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.
Time Frame
from first study treatment dose till 1 year after the treatment period
Title
Overall Response Rate (ORR)
Description
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.
Time Frame
after 6 Cycles of obinutuzumab treatment (after induction phase); each cycle is 21 days in Induction Phase;
Title
Overall Response Rate (ORR)
Description
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.
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;
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Tomasz Wróbel, MD, PhD
Phone
+48 501 419 272
Email
wrobeltw@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Dominik Dytfeld, MD, PhD
Phone
+48 602 464 708
Email
dytfeld@me.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tomasz Wróbel, MD.PhD
Organizational Affiliation
USK Wrocław
Official's Role
Principal Investigator
Facility Information:
Facility Name
Uniwersytecki Szpital kliniczy im. Jana Mikulicza-Radeckiego we Wrocławiu; Klinika Hematologii, Nowotworów Krwi Transplantacji Szpiku
City
Wrocław
State/Province
Dolnośląskie
ZIP/Postal Code
50-367
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tomasz Wróbel, MD, PhD
Phone
+48 501 419 272
Email
wrobeltw@gmail.com
First Name & Middle Initial & Last Name & Degree
Agnieszka Szeremet, MD
Phone
+48 71 784 22 77
Email
agnieszka.szeremet@wp.pl
First Name & Middle Initial & Last Name & Degree
Tomasz Wróbel, MD, PhD
First Name & Middle Initial & Last Name & Degree
Agnieszka Szeremet, MD
First Name & Middle Initial & Last Name & Degree
Elżbieta Kalicińska, MD
Facility Name
Szpital Kliniczny Przemienienia Pańskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu; Oddział Hematologii i Transplantacji Szpiku
City
Poznań
State/Province
Wielkopolskie
ZIP/Postal Code
60-569
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dominik Dytfeld, MD, PhD
Phone
+48 602464708
Email
dytfeld@me.com
First Name & Middle Initial & Last Name & Degree
Elżbieta Gwazdacz-Magiera
Phone
+48 535818919
Email
egm1@tlen.pl
First Name & Middle Initial & Last Name & Degree
Dominik Dytfeld, MD, PhD
First Name & Middle Initial & Last Name & Degree
Adam Nowicki, MD
First Name & Middle Initial & Last Name & Degree
Tomasz Szczepanik, MD
First Name & Middle Initial & Last Name & Degree
Bartosz Małecki, MD
First Name & Middle Initial & Last Name & Degree
Magdalena Matuszak, MD
12. IPD Sharing Statement
Learn more about this trial
A Study of Obinutuzumab (RO5072759) Induction in Patients With Relapsed/ Refractory Waldenström Macroglobulinemia, OBI-1
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