Obinutuzumab in Combination With GDP Chemotherapy in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma

NCT02750670 | Completed Phase 2 DMC

• 2 other identifiers: OZM-073ML29885
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a pilot study to determine the overall survival rate and toxicities of obinutuzumab given with GDP chemotherapy for relapsed or refractory CD20+ aggressive non-Hodgkin lymphoma. Patients who have CD20+ and progressed R-CHOP therapy will be enrolled into the study. About 30 patients are planned to be enrolled from Princess Margaret Cancer Centre. If the enrollment is very slow then additional site may be included. Patients will receive Obinutuzumab +GDP for 3 cycles intravenously. CT scan will be used to evaluate the response rate after cycle 2 and PET-CT will be used after cycle 3. Responders (complete metabolic response, partial metabolic response) should proceed to autologous stem cell transplant (ASCT). Patients who have progressed after three cycles or less are to have their protocol treatment discontinued, with subsequent treatment at investigator discretion. Patients will be followed up to 24 months from transplant done or last chemo. Mandatory tissue submission and optional tissue and blood submission are required for the correlative component of this study.

Conditions

Lymphoma, Non-Hodgkin's

Keywords

Lymphoma; Non-Hodgkin's; CD20+; Obinutuzumab; GDP Chemotherapy; Refractory and aggressive non-Hodgkin lymphoma

Outcome Measures

Primary Outcomes (1)

• The overall response rate (ORR) of G2DP by investigator assessment based on conventional CT imaging.

  42 days

Secondary Outcomes (8)

• The ORR rate by central review of conventional CT imaging after 2 cycles of G2DP

  42 days

• The Complete Response (CR) rate by FDG-PET scan

  Post 63 days

• The rate of successfully proceeding to autologous stem cell transplant (ASCT)

  Post 63 days

• Progression Free Survival (PFS) post ASCT (in transplanted patients) or after protocol discontinuation (in patients not transplanted).

  Up to 2 years

• The percentage of patients requiring dose reduction for hematologic toxicity.

  Up to 63 days

Study Arms (1)

GD2P

EXPERIMENTAL

Obinutuzumab 1000mg by IV for 1.5-6.5 hours with Gemcitabine 1000mg/m\^2 by IV for 30 minutes with dexamethasone 40mg by mouth daily and Cisplatin 75mg/m\^2 by IV for 1 hour all for a duration of 3 cycles

Drug: Obinutuzumab; Drug: Gemcitabine; Drug: Dexamethasone; Drug: Cisplatin

Interventions

Obinutuzumab DRUG

Type II anti-CD20 monoclonal antibody

Also known as: GAZYVA

GD2P

Gemcitabine DRUG

Antineoplastic agent

GD2P

Dexamethasone DRUG

Corticosteroid

Also known as: Decadron

GD2P

Cisplatin DRUG

Antineoplastic Agent

GD2P

Eligibility Criteria

• Age: 16 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologic diagnosis for one of the following histologies according to the World Health Organization: documented at initial diagnosis or at relapse:
• Diffuse large cell lymphoma, B-cell (includes primary mediastinal B-cell lymphoma, T-cell rich B-cell lymphoma);
• Previous indolent lymphoma (follicular lymphoma, marginal zone lymphoma, including extranodal MALT lymphoma, lymphoplasmacytoid lymphoma) with transformation to diffuse large B-cell lymphoma at relapse (biopsy proof of transformation is mandatory);
• Follicular lymphoma grade 3B;
• Biopsy proof of disease at initial diagnosis is mandatory. A biopsy at relapse is mandatory. A histological diagnosis (core or excisional biopsy) is strongly encouraged; a cytological diagnosis is acceptable only in the event that tissue cannot be obtained.
• Patients must be CD20+ in order to be eligible for the study.
• Clinically and/or radiologically measurable disease (1 site bidimensionally measurable). Measurements/ evaluations must be done within 28 days prior to registration.
• Baseline FDG-PET scan, if available, must be positive (known FDG-avid lymphoma)
• Patient must have had at least one previous regimen of therapy for their disease. Patients must have relapsed or progressed after R-CHOP chemotherapy or equivalent.
• Patient age is ≥16 years. Patients older than 70 years of age are not recommended for this study. (Note that the lower age limit at each centre will be determined by that centre's policy regarding the age at which an individual may sign his or her own consent.)
• ECOG performance status of 0, 1, 2 or 3.
• Patient must be considered fit for intensive chemotherapy and ASCT and an appropriate candidate to receive salvage chemotherapy and ASCT.
• Laboratory Requirements: (must be done within 14 days of registration)
• Hematology:
• Granulocytes (AGC) \> 1.0 x 109/L (independent of growth factor support)

You may not qualify if:

• Patients who have been previously treated with obinutuzumab.
• Life expectancy \< 90 days
• Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer and superficial bladder cancer, curatively treated in-situ cancer of the cervix or breast, or localized excised prostate cancer, other solid tumors curatively treated with no evidence of disease for \> 5 years.
• Active and uncontrolled central nervous system involvement, meningeal or parenchymal. Patients with CNS disease at initial presentation and who are in a CNS CR at the time of relapse are eligible. MRI scanning and / or lumbar puncture should be performed if there is clinical suspicion of active CNS disease.
• Patients with symptoms suggestive of Progressive Multifocal Leukoencephalopathy (PML).
• Major surgery performed within 4 weeks prior to registration.
• Known history of human immunodeficiency virus (HIV), active Hepatitis C Virus infection, active Hepatitis B Virus infection or any uncontrolled active systemic infection requiring intravenous (IV) antibiotics. Patients with positive hepatitis B serology are defined as positive Hepatitis B surface antigen (HBsAg) or core antibody (anti-HBc). These patients should consult liver disease experts before start of treatment and should be monitored and managed following local medical standards to prevent hepatitis reactivation. Patients with Hepatitis B serology suggestive of infection are eligible if they are HBV DNA negative and concurrently treated with anti-viral therapy. Patients with a past history of hepatitis C who have eradicated the virus (defined as negative PCR for HCV RNA) are eligible.
• Patients who have been vaccinated with live, attenuated vaccines within 4 weeks prior to registration.
• Known history of stroke or intracranial hemorrhage within 6 months prior to registration.
• Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification.
• Any serious active disease or co-morbid medical condition, including psychiatric illness, judged by the local investigator to preclude safe administration of the planned protocol treatment or required follow-up.
• Any other serious intercurrent illness, life threatening condition, organ system dysfunction, or medical condition judged by the local investigator to compromise the subject's safety, preclude safe administration of the planned protocol treatment or required follow-up, including (for example):
• Active, uncontrolled bacterial, fungal, or viral infection, history of chronic or recurrent infection
• Clinically significant cardiac dysfunction or cardiovascular disease.
• Patients are not eligible if they have a known hypersensitivity to the study drugs or their component, or a history of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies, or a known sensitivity or allergy to murine products

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Hoffmann-La Roche: collaborator
• Ozmosis Research Inc.: collaborator

Study Sites (1)

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Lymphoma

Interventions

obinutuzumab; Gemcitabine; Dexamethasone; Calcium Dobesilate; Cisplatin

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

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: April 15, 2016
• First Posted: April 25, 2016
• Study Start: March 15, 2017
• Primary Completion: September 9, 2020
• Study Completion: February 9, 2021
• Last Updated: June 22, 2025

Record last verified: 2025-06

Locations

CA (1)