Combination of Obinutuzumab and Venetoclax in Relapsed or Refractory DLBCL

NCT02987400 | Completed Phase 2

• 2 other identifiers: AGMT_NHL-15B2016-001760-10
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 6

Brief Summary

The purpose of this study is to evaluate the clinical activity and tolerability of a combination of obinutuzumab plus venetoclax in patients with relapsed or refractory diffuse large B-cell lymphoma.

Conditions

Lymphoma, Large B-Cell, Diffuse

Keywords

DLBCL; GA-101; ABT-199; relapsed DLBCL; refractory DLBCL; AGMT; Diffuse large B-cell lymphoma; window of opportunity

Outcome Measures

Primary Outcomes (1)

• Clinical activity and tolerability

  Objective response rate (complete or partial responses; best response) defined by PET/CT scan and bone marrow examination examination after 3 cycles.

  After 3 cycles of treatment (9 weeks)

Secondary Outcomes (6)

• Safety: Incidence of dose-limiting toxicities

  9 weeks induction plus maximum of 27 weeks consolidation

• Response duration

  From first documented response until end of follow up (max 108 weeks)

• Progression-free survival

  72 weeks after last patient last visit

• Overall survival

  72 weeks after last patient last visit

• Ability to proceed to further stem cell transplantation

  After 3 cycles of treatment (9 weeks)

Study Arms (1)

Treatment

EXPERIMENTAL

Obinutuzumab is given in a 21 day cycle intravenously starting at 1000 mg on day 1, 8 and 15 in cycle 1 and on day 1 of each following cycle Venetoclax is given orally at a dose of 800mg daily from day 1 of the first cycle.

Drug: Venetoclax; Drug: Obinutuzumab

Interventions

Venetoclax DRUG

3 cycles followed by 9 cycles consolidation if not transplant eligible

Also known as: GA-101

Treatment

Obinutuzumab DRUG

3 cycles followed by 9 cycles consolidation if not transplant eligible

Also known as: Gazyvaro

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diffuse large B-cell lymphoma (DLBCL)
• with histologically confirmed relapse within 12 months after having achieved a PR or CR with initial R-anthracycline containing therapy, or
• with refractoriness to initial R-anthracycline containing therapy (not achieving at least a partial response)
• Bcl-2 protein expression detected by immunohistochemistry.
• Adequate organ function,
• At least one bi-dimensionally measurable lesion on CT scan defined as \> 1.5 cm in its longest dimension.
• Confirmed availability of archival or freshly biopsied tumor tissue meeting protocol-defined-specifications prior to study enrolment.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2.
• Adequate hematologic function (unless caused by underlying disease, as established by extensive bone marrow involvement or as a result of hypersplenism secondary to the involvement of the spleen by lymphoma per the investigator)

You may not qualify if:

• Patient has received any other investigational treatment within 28 days before study entry.
• Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of obinutuzumab or venetoclax.
• DLBCL transformed from other malignancies or CD20 negative DLBCL.
• Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ≤ 4 weeks prior to Cycle 1 Day 1.
• Ongoing corticosteroid use \> 30 mg/day of prednisone or equivalent. Patients who received corticosteroid treatment with ≤ 30 mg/day of prednisone or equivalent must be documented to be on a stable dose of at least 4 weeks duration prior to randomization (Cycle 1 Day 1). Patients may have received a brief (\< 7 days) course of systemic steroids (≤ 100 mg prednisone equivalent) prior to initiation of study therapy for control of lymphoma-related symptoms.
• ECOG performance status ≥ 3.
• Female patients who are pregnant or breast-feeding.
• Acute or uncontrolled chronic infections.
• Known diagnosis of HIV
• Known cerebral or meningeal disease (HL or any other etiology), including signs or symptoms of PML.
• Symptomatic neurologic disease compromising normal activities of daily living or requiring medications.
• Any sensory or motor peripheral neuropathy greater than or equal to Grade 2.
• Known history of any of the following cardiovascular conditions:
• myocardial infarction within 2 years of study entry,
• New York Heart Association (NYHA) Class III or IV heart failure,

Sponsors & Collaborators

• Arbeitsgemeinschaft medikamentoese Tumortherapie: lead
• Roche Pharma AG: collaborator

Study Sites (6)

UK Graz: Universitätsklinik für Innere Medizin; Klinische Abteilung für Hämatologie

Graz, 8036, Austria

Location

Medizinische Universität Innsbruck Univ.-Klinik für Innere Medizin V Hämatologie und Onkologie

Innsbruck, 6020, Austria

Location

Kepler Universitätsklinikum Linz, Med Campus III.,Univ.-Klinik für Hämatologie und Internistische Onkologie

Linz, 4021, Austria

Location

Universitätsklinik für Innere Med. III, PMU Salzburg

Salzburg, 5020, Austria

Location

AKH Meduni Wien Universitätsklinik für Innere Medizin I Klinische Abteilung für Hämatologie und Hämostaseologie

Vienna, 1090, Austria

Location

Klinikum Wels-Grieskirchen, Abteilung für Innere Medizin IV

Wels, 4600, Austria

Location

Related Links

• Related Info

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

venetoclax; obinutuzumab

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Ulrich Jäger, MD

  Medical University of Vienna

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2016
• First Posted: December 9, 2016
• Study Start: January 4, 2017
• Primary Completion: October 19, 2021
• Study Completion: October 19, 2021
• Last Updated: February 16, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (6)