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Trial record 1 of 1 for:    itself Selicrelumab
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Study of Intratumoral Selicrelumab With Atezolizumab in Patients With Refractory or Relapsed B Cell Lymphoma

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ClinicalTrials.gov Identifier: NCT03892525
Recruitment Status : Recruiting
First Posted : March 27, 2019
Last Update Posted : January 7, 2020
Sponsor:
Collaborator:
Roche Pharma AG
Information provided by (Responsible Party):
The Lymphoma Academic Research Organisation

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

Condition or disease Intervention/treatment Phase
Recurrent B-Cell Non-Hodgkin Lymphoma Refractory B-Cell Non-Hodgkin Lymphoma Drug: Selicrelumab Drug: Atezolizumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 44 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase Ib Study Evaluating the Safety and Efficacy of Intratumoral Agonistic Anti-CD40 (Selicrelumab) in Combination With Anti-PDL1 (Atezolizumab) in Patients With Refractory or Relapsed B Cell Lymphoma
Actual Study Start Date : July 4, 2019
Estimated Primary Completion Date : September 15, 2020
Estimated Study Completion Date : June 15, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: treatment Drug: Selicrelumab
escalated dose in intratumoral injection, every 3 weeks, for 3 cycles

Drug: Atezolizumab
1200mg IV every 3 week until progression or relapse for maximum 1 year
Other Name: Tecentriq




Primary Outcome Measures :
  1. optimal dose of intratumoral Selicrelumab in combination with flat doses of Atezolizumab IV [ Time Frame: 21 days (1 cycle) ]

Secondary Outcome Measures :
  1. complete metabolic response rate (CMR) [ Time Frame: 2 months ]
  2. complete metabolic response rate (CMR) [ Time Frame: 4 months ]
  3. complete metabolic response rate (CMR) [ Time Frame: 8 months ]
  4. complete metabolic response rate (CMR) [ Time Frame: 13 months ]
  5. overall metabolic response rate (OMR) [ Time Frame: 2 months ]
  6. overall metabolic response rate (OMR) [ Time Frame: 4 months ]
  7. overall metabolic response rate (OMR) [ Time Frame: 8 months ]
  8. overall metabolic response rate (OMR) [ Time Frame: 13 months ]
  9. Best overall metabolic response (BOMR) [ Time Frame: 4 months ]
  10. duration of response (DOR) [ Time Frame: 2 years ]
  11. progression free survival (PFS) [ Time Frame: 2 years ]
  12. overall survival (OS) [ Time Frame: 2 years ]
  13. Number of serious adverse event (SAE) [ Time Frame: 16 months ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Aged 18 and older
  2. Histologically confirmed diagnosis of recurrent or refractory B-non-Hodgkin's lymphoma (NHL)
  3. 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.

  4. 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).
  5. 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)
  6. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1
  7. Signed written informed consent
  8. Life expectancy ≥ 3 months
  9. Patients must have recovered to ≤ grade 1 from all toxicities related to prior treatments excluding alopecia.
  10. Patients must be naïve from immunotherapy with anti-PD1/PDL1 or agonistic anti-CD40 therapy
  11. Adequate laboratory parameters:

    • Hb ≥ 9 g/dl
    • absolute neutrophil count (ANC) ≥ 1000/μL
    • Platelet count ≥ 50,000/μL
    • Total bilirubin < 2.5 times the institutional upper limit of normal (ULN) (3.5 x ULN if liver involvement)
    • Hepatic enzymes (aspartate aminotransferase (AST), alanine aminotransferase (ALT) ) ≤ 2.5 x ULN (5 x ULN if liver involvement)
    • Serum creatinine < 2.0 x ULN or creatinine clearance >50 mL/mn
    • International Normalized Ratio (INR) and Partial Thromboplastin Time (PTT) >1.5 × ULN
  12. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 72 hours prior to the start of study drug administration.
  13. Persons of reproductive potential must agree to use an adequate method of contraception throughout treatment and for at least 6 months after study drug is stopped.

    *Highly effective method includes: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation 1 (oral/ intravaginal/ transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation 1 (oral/injectable/implantable); intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomised partner; sexual abstinence

  14. Patient covered by any social security system (France)
  15. Patient who understands and speaks one of the country official language

Exclusion Criteria:

  1. Immature B cell malignancies (B-acute lymphoblastic leukemia (ALL), Burkitt lymphoma) and T-cell lymphomas
  2. 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
  3. Use of any standard or experimental anti-cancer drug therapy within 4 weeks prior to the first scheduled treatment dose (C1D1).
  4. History of treatment with anti-PD1 or anti-PDL1.
  5. 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
  6. 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)
  7. left ventricular ejection fraction (LVEF) < 45% as determined by echocardiography or multiple uptake gated acquisition (MUGA) scan
  8. Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
  9. 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)
  10. Recent (< 1 month ago) clinically significant infection, active tuberculosis or antibiotics therapy
  11. 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.
  12. 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.
  13. Psychiatric, other medical illness or other condition that in the opinion of the PI prevents compliance with study procedures or ability to provide valid informed consent
  14. Use of anti-coagulant agents or history a significant bleeding diathesis. If a superficial lymph node or subcutaneous mass is to be injected, patients on agents such as non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, or clopidogrel are eligible and these agents do not have to be withheld. For procedures with moderate or significant risk of bleeding, long-acting agents such as aspirin or clopidogrel should be discussed with the Sponsor and may need to be discontinued before Selicrelumab therapy. Patients under preventive dose of low molecular weight heparin (LMWH) are eligible if they can stop their treatment 24h prior the IT injection and restart 24h after the injection. No anticoagulant restriction for patients with injected lesions being superficial tumor lesions eligible for at least 5mn mechanical compression after tumor biopsy & injections (as in routine interventional radiology practice).
  15. Subcapsular liver tumor lesions of tumor encased vessels or not eligible for intratumoral biopsies or injections.
  16. Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during Atezolizumab treatment or within 5 months after the last dose of Atezolizumab
  17. Prior allogeneic hematopoietic stem cell transplantation
  18. Patients who have undergone a solid organ transplant
  19. Documented infection with HIV
  20. Positive serology to hepatitis B. Patients with previous and cured infections are not eligible. Patients who are seropositive due to a history of hepatitis B vaccine are eligible.
  21. History or presence of an abnormal ECG that is clinically significant in the investigator's opinion, including complete left bundle branch block, second- or third degree heart block, or evidence of prior myocardial infarction
  22. Person deprived of his/her liberty by a judicial or administrative decision
  23. Person hospitalized without consent
  24. Adult person under legal protection
  25. Adult person unable to provide informed consent because of intellectual impairment, any serious medical condition, laboratory abnormality or psychiatric illness
  26. Pregnant or nursing women

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): NCT03892525


Contacts
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Contact: Ombeline Vérité +33 (0)4 72 66 93 33 verite.ombeline@lysarc.org

Locations
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France
APHP - Hôpital Henri Mondor Recruiting
Créteil, France
Contact: François LEMONNIER         
CHU de Montpellier Recruiting
Montpellier, France
Contact: Guillaume Cartron         
Hospices Civils de Lyon - Centre Hospitalier Lyon Sud Recruiting
Pierre-Bénite, France
Contact: Emmanuel Bachy         
CHU de Rennes - Hôpital Pontchaillou Recruiting
Rennes, France
Contact: Roch Houot         
Institut Gustave Roussy Not yet recruiting
Villejuif, France
Contact: Aurélien Marabelle         
Sponsors and Collaborators
The Lymphoma Academic Research Organisation
Roche Pharma AG
Investigators
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Study Chair: Roch HOUOT, Pr CHU Rennes

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Responsible Party: The Lymphoma Academic Research Organisation
ClinicalTrials.gov Identifier: NCT03892525    
Other Study ID Numbers: ITSELF
First Posted: March 27, 2019    Key Record Dates
Last Update Posted: January 7, 2020
Last Verified: January 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Atezolizumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs