Atezolizumab, Rituximab, Gemcitabine and Oxaliplatin in Patients With Relapsed or Refractory DLBCL Not Suitable for High-dose Therapy

NCT03422523 | Terminated Phase 2 DMC

• 2 other identifiers: RHM CAN12192016-002654-21
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates the addition of Atezolizumab to current therapy of Rituximab, Gemcitabine and Oxaliplatin (R-GemOx) for patients with relapsed or refractory Diffuse Large B-Cell Lymphoma (DLBCL) that are not candidates for high-dose therapy. All patients will receive one cycle of R-GemOx. Three quarters of patients (Arm B) will go on to have a further 5 cycles (every 14 days) of R-GemOx with Atezolizumab, with one quarter of patients (Arm A) continuing with 5 cycles of R-GemOx. The patients in Arm B will continue to have Atezolizumab every 21 days for 8 cycles whilst Arm A patients will enter an observational phase during this time. Follow up will begin at 12 months from initial treatment until month 32.

Conditions

Diffuse Large B Cell Lymphoma; Relapsed Diffuse Large B-Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma

Keywords

Refractory; Relapsed; Hematological cancer

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  Progression free survival will be measured from patient notes, from the day of registration to the date of progression or death from any cause. Patients who do not die will be censored at their date of last follow up.

  From date of registration until the date of first documented progression or date of death from any cause, whichever came first, up to follow up at month 36.

Secondary Outcomes (3)

• AE's reported and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) for R-GemOx-Atezo

  At all visits from baseline to follow up month 36

• Lugano classification lymphoma response criteria (LYRIC) to PET/CT

  Baseline and cycle 3 day 8, cycle 3 day 8 and week 42, week 42 and 12 month follow up, 12 month follow up and 24 month follow up

• Overall survival

  From date of registration until the date of first documented progression or date of death from any cause, whichever came first, up to follow up at month 36.

Other Outcomes (7)

• Whole transcriptome profiling

  Baseline

• Double staining techniques

  Baseline

• Flow Cytometry

  day 1 of cycles 1, 2, 3, and 5, week 15, day 1 of weeks 17, 23, 29, 35 and 42 only

Study Arms (2)

Arm A Control

ACTIVE COMPARATOR

6 Cycles of R-GemOx (Rituximab, Gemcitabine and Oxaliplatin) every 14 days.

Drug: Rituximab; Drug: Gemcitabine 1000 mg; Drug: Oxaliplatin 100 MG

Arm B Experimental

EXPERIMENTAL

1 Cycle of R-GemOx (Rituximab, Gemcitabine and Oxaliplatin) followed by 5 cycles of R-GemOx with Atezolizumab every 14 days. Followed by 8 maintenance cycles of Atezolizumab every 21 days.

Drug: Atezolizumab; Drug: Rituximab; Drug: Gemcitabine 1000 mg; Drug: Oxaliplatin 100 MG

Interventions

Atezolizumab DRUG

Intravenous drip

Also known as: Tecentriq

Arm B Experimental

Rituximab DRUG

Intravenous drip/or Subcutaneous from cycle 2

Also known as: Mabthera

Arm A Control; Arm B Experimental

Gemcitabine 1000 mg DRUG

intravenous drip

Arm A Control; Arm B Experimental

Oxaliplatin 100 MG DRUG

intravenous drip

Arm A Control; Arm B Experimental

Eligibility Criteria

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

You may qualify if:

• Histologically proven CD20 +ve diffuse large B-cell lymphoma with sufficient diagnostic material, obtained either at diagnosis or relapse (the latter is preferable) that is available to forward to the Haematological Malignancies Diagnostic Service (HMDS) for gene expression profiling and central pathology review. (See screening procedure for details on biopsy requirements)
• Refractory to, or relapsed following, first-line or second-line treatments with rituximab concurrently with anthracycline or anthracenedione-based chemotherapy (etoposide or gemcitabine allowed if comorbid).
• Refractory disease must fulfil one of the following:
• Continuing partial response (PR) from termination of first-line treatment. It is strongly recommended the lymphoma be reconfirmed by biopsy however, if these procedures are deemed to be inappropriate, the CI may determine eligibility following review of the imaging results and disease history.
• Continuing stable disease (SD) from termination of first-line treatment. Reconfirmation of the lymphoma by biopsy (preferred) is recommended but not mandatory.
• Progressive disease (PD). Biopsy or reconfirmation of the lymphoma is recommended but not mandatory.
• o Not eligible for high-dose therapy with peripheral blood progenitor cell rescue at Investigator discretion as a result of:
• Age
• Co-morbidity
• Previous HDT. Rationale to be clearly documented on eCRF and medical notes.
• Baseline FDG-PET scans must demonstrate positive lesions compatible with CT defined anatomical tumour sites.
• CT/PET scan showing at least:
• or more clearly demarcated lesions/nodes with a long axis \>1.5cm and short axis ≥1.0cm OR
• clearly demarcated lesion/node with a long axis \>2.0cm and short axis ≥1.0cm.
• Resolution of toxicities from previous therapy to a grade that in the opinion of the investigator does not contraindicate study participation.

You may not qualify if:

• Received any of the following treatments within two weeks prior to start of study therapy (unless otherwise stated):
• Anti-cancer cytotoxics (excluding corticosteroids)
• Radiotherapy unless it is to a limited field to control life/organ-threatening symptoms.
• DLBCL that is refractory to or relapsed within 3 months of a gemcitabine regimen for DLBCL
• Major surgery within 4 weeks of registration.
• Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half-lives or 4 weeks prior to registration.
• History of stroke or intracranial haemorrhage within 6 months prior to registration.
• Pre-existing peripheral neuropathy grade \>2.
• Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to registration, congestive heart failure (NYHA III-IV), a current LVEF of \<40%
• Significant concurrent, uncontrolled medical condition that in the opinion of the investigator contraindicates participation in this study
• Known lymphoma involvement of the CNS.
• Known or suspected hypersensitivity to study treatments that in the opinion of the investigator contraindicates their participation. Patients with known history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug induced pneumonitis or idiopathic pneumonitis, or evidence of active pneumonitis will be excluded from study participation.
• Known HIV positivity; positive serology for Hep B (defined as positivity for Hepatitis B surface antigen (HBsAg) or Hepatitis B core antibody (anti-HBc)) or C; chronic or current infectious disease (except evidence of prior vaccination).
• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection or any major episode of infection requiring treatment with IV antibiotics or hospitalization within 2 weeks of the start of Cycle 1. Suspected active or latent tuberculosis needs to be confirmed by positive interferon gamma (IFN-gamma) release assay.
• Other past or current malignancy within 2 years prior to registration unless in the opinion of the investigator it does not contraindicate participation in the study. Subjects who have a history of completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma, are eligible.

Sponsors & Collaborators

• University Hospital Southampton NHS Foundation Trust: lead
• Hoffmann-La Roche: collaborator

Study Sites (1)

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Recurrence

Interventions

atezolizumab; Rituximab; Gemcitabine; Oxaliplatin

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; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals

Study Officials

• Andy Davies

  Southampton University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 11, 2018
• First Posted: February 5, 2018
• Study Start: May 9, 2018
• Primary Completion: January 31, 2021
• Study Completion: November 18, 2021
• Last Updated: August 22, 2022

Record last verified: 2022-08

Locations

GB (1)