Study of Intratumoral Selicrelumab With Atezolizumab in Patients With Refractory or Relapsed B Cell Lymphoma

NCT03892525 | Terminated Phase 1 DMC

• 1 other identifier: ITSELF
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 5

Brief Summary

This is a multicenter, open, dose escalation phase Ib trial of intratumoral agonistic anti-CD40 Ab (Selicrelumab intratumoral every 3 weeks for 3 cycles) in combination with anti-PDL1 Ab (Atezolizumab 1200mg intravenous every 3 weeks) in patients with refractory or relapsed B cell lymphoma

Conditions

Recurrent B-Cell Non-Hodgkin Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• optimal dose of intratumoral Selicrelumab in combination with flat doses of Atezolizumab IV

  21 days (1 cycle)

Secondary Outcomes (13)

• complete metabolic response rate (CMR)

  2 months

• complete metabolic response rate (CMR)

  4 months

• complete metabolic response rate (CMR)

  8 months

• complete metabolic response rate (CMR)

  13 months

• overall metabolic response rate (OMR)

  2 months

Study Arms (1)

treatment

EXPERIMENTAL

Drug: Selicrelumab; Drug: Atezolizumab

Interventions

Selicrelumab DRUG

escalated dose in intratumoral injection, every 3 weeks, for 3 cycles

treatment

Atezolizumab DRUG

1200mg IV every 3 week until progression or relapse for maximum 1 year

Also known as: Tecentriq

treatment

Eligibility Criteria

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

You may qualify if:

• Aged 18 and older
• Histologically confirmed diagnosis of recurrent or refractory B-non-Hodgkin's lymphoma (NHL)
• At least one injectable lesion:
• i) at least one nodal lesion amenable to intratumoral injection and biopsy (including deep lesions accessible by interventional radiology either under US or CT-scan guidance). The first injected lesion should be of at least 2 x 1.5 cm in diameter. The subsequent lesions to be injected should be ≥1.5 cm in diameter. Extra nodal lesions will not be considered as injectable lesion.
• ii) OR One cutaneous lesion of at least ≥ 1 cm in diameter. Other extra nodal lesion will not be considered as injectable lesion.
• Patient must have a 18-F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose (FDG) avid lymphoma that can be followed by positron emission tomography (PET).
• Bi-dimensionally measurable disease defined by at least one measurable lesion according to Lugano criteria, with at least 1cm in its shortest diameter and 1.5cm in largest diameter (different from the lesion that will be injected)
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1
• Signed written informed consent
• Life expectancy ≥ 3 months
• Patients must have recovered to ≤ grade 1 from all toxicities related to prior treatments excluding alopecia.
• Patients must be naïve from immunotherapy with anti-PD1/PDL1 or agonistic anti-CD40 therapy
• Adequate laboratory parameters:
• Hb ≥ 9 g/dl
• absolute neutrophil count (ANC) ≥ 1000/μL

You may not qualify if:

• Immature B cell malignancies (B-acute lymphoblastic leukemia (ALL), Burkitt lymphoma) and T-cell lymphomas
• History of severe allergic anaphylactic reactions to chimeric, human or humanized antibodies, or fusion proteins or known hypersensitivity to Chinese hamster ovarian (CHO) cell products or any component of the Atezolizumab formulation. Patients with a known allergy to either of the drugs individually
• Use of any standard or experimental anti-cancer drug therapy within 4 weeks prior to the first scheduled treatment dose (C1D1).
• History of treatment with anti-PD1 or anti-PDL1.
• Significant immunosuppression from:
• Concurrent, recent (≤ 2 weeks ago) or anticipated treatment with systemic corticosteroids at dose \>10mg/day of prednisolone (or equivalent)
• Other immunosuppressive medications such as methotrexate, cyclosporine, azathioprine
• Any immunosuppressive condition such as common variable hypogammaglobulinemia
• Myocardial infarction within 6 months prior to first study drug, active cardiac ischemia or New York Heart Association (NYHA) Grade III or IV heart failure, severe arrhythmia, unstable arrhythmias, or unstable angina) or pulmonary disease (including uncontrolled obstructive pulmonary disease and history of bronchospasm or other according to investigator's decision)
• left ventricular ejection fraction (LVEF) \< 45% as determined by echocardiography or multiple uptake gated acquisition (MUGA) scan
• Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
• Prior history of other cancer other than lymphoma within 2 years (except basal cell carcinoma, in situ squamous and non-squamous cell carcinomas completely resected (R0) and prostate cancers with normal results for more than 6 months)
• Recent (\< 1 month ago) clinically significant infection, active tuberculosis or antibiotics therapy
• Central nervous system involvement with lymphoma, including parenchymal and leptomeningeal disease. Patients with asymptomatic focal epiduritis on imaging might be included with the Sponsor's approval.
• Ongoing or history of autoimmune disease, including active non-infectious pneumonitis, with the exception of alopecia, vitiligo, auto-immune endocrine deficiency with stable hormone replacement therapy, controlled skin eczema and stable asymptomatic and treated asthma. Patients with severe auto-immune disease in one of their parents, siblings, or children will not be eligible.

Sponsors & Collaborators

• The Lymphoma Academic Research Organisation: lead
• Roche Pharma AG: collaborator

Study Sites (5)

APHP - Hôpital Henri Mondor

Créteil, France

Location

CHU de Montpellier

Montpellier, France

Location

Hospices Civils de Lyon - Centre Hospitalier Lyon Sud

Pierre-Bénite, France

Location

CHU de Rennes - Hôpital Pontchaillou

Rennes, France

Location

Institut Gustave Roussy

Villejuif, France

Location

MeSH Terms

Conditions

Lymphoma, B-Cell

Interventions

selicrelumab; atezolizumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Roch HOUOT, Pr

  CHU Rennes

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2019
• First Posted: March 27, 2019
• Study Start: July 4, 2019
• Primary Completion: April 7, 2021
• Study Completion: April 7, 2021
• Last Updated: July 26, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (5)