Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02750670
Recruitment Status : Active, not recruiting
First Posted : April 25, 2016
Last Update Posted : September 26, 2018
Sponsor:
Collaborators:
Hoffmann-La Roche
Ozmosis Research Inc.
Information provided by (Responsible Party):
University Health Network, Toronto

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.


Condition or disease Intervention/treatment Phase
Lymphoma, Non-Hodgkin's Drug: Obinutuzumab Drug: Gemcitabine Drug: Dexamethasone Drug: Cisplatin Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study of Obinutuzumab in Combination With GDP Chemotherapy for the Treatment of Relapsed or Refractory CD20+ Aggressive Non-Hodgkin Lymphoma
Actual Study Start Date : March 15, 2017
Estimated Primary Completion Date : May 2020
Estimated Study Completion Date : May 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: GD2P
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
Type II anti-CD20 monoclonal antibody
Other Name: GAZYVA

Drug: Gemcitabine
Antineoplastic agent

Drug: Dexamethasone
Corticosteroid
Other Name: Decadron

Drug: Cisplatin
Antineoplastic Agent




Primary Outcome Measures :
  1. The overall response rate (ORR) of G2DP by investigator assessment based on conventional CT imaging. [ Time Frame: 42 days ]

Secondary Outcome Measures :
  1. The ORR rate by central review of conventional CT imaging after 2 cycles of G2DP [ Time Frame: 42 days ]
  2. The Complete Response (CR) rate by FDG-PET scan [ Time Frame: Post 63 days ]
  3. The rate of successfully proceeding to autologous stem cell transplant (ASCT) [ Time Frame: Post 63 days ]
  4. Progression Free Survival (PFS) post ASCT (in transplanted patients) or after protocol discontinuation (in patients not transplanted). [ Time Frame: Up to 2 years ]
  5. The percentage of patients requiring dose reduction for hematologic toxicity. [ Time Frame: Up to 63 days ]
  6. Correlative studies on patient specimens markers of disease response (in tumor and blood/plasma) as well as to identify blood/plasma markers that provide additional discriminative information to FDG-PET scans [ Time Frame: Up to 2 years ]
  7. The Complete Response (CR) rate by central review of conventional CT imaging after 2 cycles of G2DP [ Time Frame: 42 days ]
  8. Overall Survival (OS) post ASCT (in transplanted patients) or after protocol discontinuation (in patients not transplanted). [ Time Frame: Up to 2 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   16 Years to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.

  2. 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)

  3. 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.
  4. 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.)
  5. ECOG performance status of 0, 1, 2 or 3.
  6. Patient must be considered fit for intensive chemotherapy and ASCT and an appropriate candidate to receive salvage chemotherapy and ASCT.
  7. Laboratory Requirements: (must be done within 14 days of registration)

    Hematology:

    • Granulocytes (AGC) > 1.0 x 109/L (independent of growth factor support)
    • Platelets > 100 x 109/L (50 x 109/L if bone marrow involvement by lymphoma, independent of transfusion support)

    Biochemistry:

    • AST and ALT < 3x ULN
    • Serum total bilirubin < 1.5x ULN (≤ 5x ULN if Gilberts Disease)
    • Serum Creatinine < 1.5x ULN (or estimated GFR of ≥40 mL/min/1.73m2 using Cockcroft Gault formula)
    • International normalized ratio (INR) > 1.5 × the ULN in the absence of therapeutic anticoagulation
    • Partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT)
    • > 1.5 × the ULN in the absence of a lupus anticoagulant
  8. A Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) and is not postmenopausal. Menopause is defined as 12 months of amenorrhea in a woman over age 45 years in the absence of other biological or physiological causes. Women of child bearing potential (who are heterosexually active) and men (who are sexually active with WOCBP), must be practicing a highly effective method of birth control (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 in female patients for 18 months after end of antibody treatment Men must agree to not donate sperm during and after the study. These restrictions apply for 18 months after the last dose of study drug.

    Women of childbearing potential must have a pregnancy test taken (either by serum beta-human chorionic gonadotropin [β-hCG]) or urine) and proven negative within 14 days prior to registration.

    Women who are pregnant or breastfeeding are ineligible for this study.

  9. Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate.
  10. Patients must be accessible for treatment and follow-up. Patients randomized on this trial must be treated and followed at the participating centre. Investigators must assure themselves the patients randomized on this trial will be available for complete documentation of the treatment, response assessment, adverse events, and follow-up.
  11. Protocol treatment is to begin within 5 working days of patient registration

Exclusion Criteria:

  1. Patients who have been previously treated with obinutuzumab.
  2. Life expectancy < 90 days
  3. 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.
  4. 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.
  5. Patients with symptoms suggestive of Progressive Multifocal Leukoencephalopathy (PML).
  6. Major surgery performed within 4 weeks prior to registration.
  7. 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.
  8. Patients who have been vaccinated with live, attenuated vaccines within 4 weeks prior to registration.
  9. Known history of stroke or intracranial hemorrhage within 6 months prior to registration.
  10. 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.
  11. 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.
  12. 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.
  13. 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02750670


Locations
Layout table for location information
Canada, Ontario
Princess Margaret Cancer Centre
Toronto, Ontario, Canada
Sponsors and Collaborators
University Health Network, Toronto
Hoffmann-La Roche
Ozmosis Research Inc.

Layout table for additonal information
Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT02750670     History of Changes
Other Study ID Numbers: OZM-073
ML29885 ( Other Grant/Funding Number: Roche )
First Posted: April 25, 2016    Key Record Dates
Last Update Posted: September 26, 2018
Last Verified: September 2018

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Health Network, Toronto:
Lymphoma
Non-Hodgkin's
CD20+
Obinutuzumab
GDP Chemotherapy
Refractory and aggressive non-Hodgkin lymphoma

Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cisplatin
Dexamethasone
Gemcitabine
Obinutuzumab
Antineoplastic Agents
Dexamethasone acetate
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites