A Study of Obinutuzumab (RO5072759) Induction in Patients With Relapsed/ Refractory Waldenström Macroglobulinemia, OBI-1

NCT ID: NCT03679455

Last Updated: 2018-11-13

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-21
• Study Completion Date: 2022-12-31

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)

Conditions

Waldenstrom Macroglobulinemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment arm

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

Group Type: EXPERIMENTAL

Obinutuzumab 25 MG/ML

Intervention Type: DRUG

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.

Interventions

Obinutuzumab 25 MG/ML

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.

Intervention Type: DRUG

Other Intervention Names

Gazyvaro

Eligibility 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 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

7. 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

8. 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

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 < 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

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Roche Pharma AG

INDUSTRY

Sponsor Role: collaborator

Bioscience, S.A.

INDUSTRY

Sponsor Role: collaborator

Polish Myeloma Consortium

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tomasz Wróbel, MD.PhD

Role: PRINCIPAL_INVESTIGATOR

USK Wrocław

Locations

Szpital Kliniczny Przemienienia Pańskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu; Oddział Hematologii i Transplantacji Szpiku

Poznan, Greater Poland Voivodeship, Poland

Site Status: RECRUITING

Uniwersytecki Szpital kliniczy im. Jana Mikulicza-Radeckiego we Wrocławiu; Klinika Hematologii, Nowotworów Krwi Transplantacji Szpiku

Wroclaw, Lower Silesian Voivodeship, Poland

Site Status: RECRUITING

Countries

Poland

Central Contacts

Tomasz Wróbel, MD, PhD

Role: CONTACT

wrobeltw@gmail.com

+48 501 419 272

Dominik Dytfeld, MD, PhD

Role: CONTACT

dytfeld@me.com

+48 602 464 708

Facility Contacts

Dominik Dytfeld, MD, PhD

Role: primary

dytfeld@me.com

+48 602464708

Elżbieta Gwazdacz-Magiera

Role: backup

egm1@tlen.pl

+48 535818919

Tomasz Wróbel, MD, PhD

Role: primary

wrobeltw@gmail.com

+48 501 419 272

Agnieszka Szeremet, MD

Role: backup

agnieszka.szeremet@wp.pl

+48 71 784 22 77

References

Wrobel T, Kalicinska E, Zaucha JM, Morawska M, Giannopoulos K, Jamroziak K, Lech-Maranda E, Taszner M, Szeremet A, Malecki B, Druzd-Sitek A, Lojko-Dankowska A, Dytfeld D. Obinutuzumab induction and maintenance in patients with Waldenstrom macroglobulinaemia: an open-label, single-arm phase 2 study. EClinicalMedicine. 2025 Jul 25;86:103383. doi: 10.1016/j.eclinm.2025.103383. eCollection 2025 Aug.

Reference Type: DERIVED

PMID: 40756965 (View on PubMed)

Other Identifiers

ML39235

Identifier Type: -

Identifier Source: org_study_id