A trial to assess whether the addition of atezolizumab to current standard treatment for patients with relapsed or refractory Diffuse Large B-Cell Lymphoma, who are not able to have high dose therapy, improves survival outcomes

Conditions

Lymphoma Cancer Cancer

Thomas Cummin, Joshua Caddy, Katy Mercer, Tom Maishman, Anna Schuh et al. (15 authors)

Hematological Oncology2019-06-014 citations

ARGO: A RANDOMISED PHASE II STUDY OF ATEZOLIZUMAB WITH RITUXIMAB, GEMCITABINE AND OXALIPLATIN IN PATIENTS WITH RELAPSED OR REFRACTORY DIFFUSE LARGE B‐CELL LYMPHOMA WHO ARE NOT CANDIDATES FOR HIGH‐DOSE THERAPY

Andrew Davies, O. Tansley Hancock, Thomas Cummin, Joshua Caddy, Louise Stanton et al. (12 authors)

Hematological Oncology2019-06-011 citations

10.1002/hon.1_2632

Abstract CT162: ACCEPT: A phase Ib/II combination of acalabrutinib with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) for patients with diffuse large B-cell lymphoma (DLBCL)

Peter Johnson, Joshua Caddy, Tom Cumin, Bridgen Merton, Tom Maishman et al. (8 authors)

Cancer Research2018-07-012 citations

10.1158/1538-7445.am2018-ct162

Interventions

Participants are randomly allocated to one of two treatment arms: Arm A or Arm B. Treatment involves 1 cycle of rituximab-gemcitabine-oxaliplatin for all patients. For those in the A

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: Current participant inclusion criteria as of 05/07/2019: 1 Histologically proven CD20 +ve diffuse large B-cell lymphoma (including transformation of previous low-grade lymphoma and primary mediastinal B-cell lymphoma), preferably with sufficient diagnostic material, available to forward to the Haematological Malignancies Diagnostic Service (HMDS). (See screening procedure for details on biopsy requirements) 2. 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). Patients who have received further lines of treatment may be included. Refractory disease must fulfil one of the following: 2.1 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. 2.2 Continuing stable disease (SD) from termination of first-line treatment. Reconfirmation of the lymphoma by biopsy (preferred) is recommended but not mandatory. 2.3 Progressive disease (PD). Biopsy or reconfirmation of the lymphoma is recommended but not mandatory. 3. Not eligible for high-dose therapy with peripheral blood progenitor cell rescue at Investigator discretion as a result of: (a) Age; (b) Co-morbidity; (c) Previous HDT.Rationale to be clearly documented on eCRF and medical notes. 4. Baseline FDG-PET scans must demonstrate positive lesions compatible with CT defined anatomical tumour sites. 5. CT/PET scan showing at least: 2 or more clearly demarcated lesions/nodes with a long axis >1.5cm and short axis =1.0cm OR 1 clearly demarcated lesion/node with a long axis >2.0cm and short axis =1.0cm. 6. Resolution of toxicities from previous therapy to a grade that in the opinion of the investigator does not contraindicate study participation. 7. Patients aged 16 years or over. 8. Willingness to participate in appropriate pregnancy prevention measures. 8.1Female patients who are fertile and of childbearing potential must have a negative serum or urine pregnancy test during screening (within 14 days prior to the start of trial treatment) and agree to use two highly effective forms of contraception (oral, injected or implanted hormonal contraception and condom; an intra-uterine device and condom) effective from the first administration of all study drugs, throughout the trial and for 12 months after last dose of study therapy are considered eligible. Unless they are surgically sterile or = 2 years after the onset of menopause. 8.2 Male patients with partners of child-bearing potential who agree to take measures not to father children by using two forms of highly effective contraception (oral, injected or implanted hormonal contraception and condom; an intra-uterine device and condom) effective from the first administration of all study drugs, throughout the trial and for 12 months after last dose of study therapy are considered eligible. Male subjects must also refrain from donating sperm during this period. Unless they are surgically sterile.

Exclusion criteria

Exclusion criteria: Current participant exclusion criteria as of 05/07/2019: 1 Received any of the following treatments within two weeks prior to start of study therapy (unless otherwise stated): 1.1 Anti-cancer cytotoxics (excluding corticosteroids) 1.2 Radiotherapy unless it is to a limited field to control life/organ-threatening symptoms. 2. DLBCL that is refractory to or relapsed within 3 months of a gemcitabine regimen for DLBCL 3. Major surgery within 4 weeks of registration. 4. Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half-lives or 4 weeks prior to registration. 5. History of stroke or intracranial haemorrhage within 6 months prior to registration. 6. Pre-existing peripheral neuropathy grade >2. 7. 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 2.0 times upper normal limit (unless due to lymphoma or unless creatinine clearance >60mL/min) 14.5 Total bilirubin >1.5 times upper normal limit (unless due to lymphoma or a known history of Gilbert’s disease, no higher than >3 times upper normal limit) 14.6 ALT/AST >2.5 times upper normal limit (unless due to lymphoma, no higher than >5 times upper normal limit) 14.7 Alkaline phosphatase >2.5 times upper

Design outcomes

Primary

Measure	Time frame
Progression free-survival rate is measured using patient notes at 1 year from study entry.	—

Secondary

Measure	Time frame
1. The toxicity and causality of each adverse event (AE) with R-GemOx-Atezo is measured and severity graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) at Cycles 2-6, End of Treatment, Maintenance cycles 1-8, week 42, and during follow up visits at month 12, 16, 20, 24, 30 and 36 for patients in Arm B 2. Objective response (partial or complete metabolic response (PR or CR)) is assessed by PET in any of the patients as determined by the Lugano response criteria at Baseline, End of Treatment and at the End of Maintenance in week 42 3. Progression free survival from study entry will be measured from the day of registration to the date of progression or death from any cause using patient notes. Patients who do not die will be censored at their date of last follow up. 4. Overall survival from study entry ismeasured from the day of registration to the date of death from any cause from patient notes. Patients who do not die are censored at their date of last follow up.	—

Measure

Time frame

1. The toxicity and causality of each adverse event (AE) with R-GemOx-Atezo is measured and severity graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) at Cycles 2-6, End of Treatment, Maintenance cycles 1-8, week 42, and during follow up visits at month 12, 16, 20, 24, 30 and 36 for patients in Arm B 2. Objective response (partial or complete metabolic response (PR or CR)) is assessed by PET in any of the patients as determined by the Lugano response criteria at Baseline, End of Treatment and at the End of Maintenance in week 42 3. Progression free survival from study entry will be measured from the day of registration to the date of progression or death from any cause using patient notes. Patients who do not die will be censored at their date of last follow up. 4. Overall survival from study entry ismeasured from the day of registration to the date of death from any cause from patient notes. Patients who do not die are censored at their date of last follow up.

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Countries

United Kingdom

Outcome results

None listed