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Recurrent B-Cell Non-Hodgkin LymphomaPhase 1NCT03892525

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

A Phase 1 study testing Selicrelumab and Atezolizumab in people with Recurrent B-Cell Non-Hodgkin Lymphoma and Refractory B-Cell Non-Hodgkin Lymphoma, run by The Lymphoma Academic Research Organisation at 5 sites in France.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Selicrelumab and Atezolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4 participants
Where
5 sitesFrance
Study dates
4 Jul 2019to 7 Apr 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Aged 18 and older
  • Histologically confirmed diagnosis of recurrent or refractory B-non-Hodgkin's lymphoma (NHL)
  • At least one injectable lesion:
  • 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.
  • 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).
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  • 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
  • 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
  • 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.
  • 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
  • Patient covered by any social security system (France)
  • Patient who understands and speaks one of the country official language

Who cannot join

  • 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)
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  • 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.
  • 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
  • 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).
  • Subcapsular liver tumor lesions of tumor encased vessels or not eligible for intratumoral biopsies or injections.
  • 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
  • Prior allogeneic hematopoietic stem cell transplantation
  • Patients who have undergone a solid organ transplant
  • Documented infection with HIV
  • 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.
  • 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
  • Person deprived of his/her liberty by a judicial or administrative decision
  • Person hospitalized without consent
  • Adult person under legal protection
  • Adult person unable to provide informed consent because of intellectual impairment, any serious medical condition, laboratory abnormality or psychiatric illness
  • Pregnant or nursing women

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

France5 sites

  • APHP - Hôpital Henri Mondor

    Créteil

  • CHU de Montpellier

    Montpellier

  • Hospices Civils de Lyon - Centre Hospitalier Lyon Sud

    Pierre-Bénite

  • CHU de Rennes - Hôpital Pontchaillou

    Rennes

  • Institut Gustave Roussy

    Villejuif

Other trials in France

About this study

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

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

Being tested
Selicrelumab, Atezolizumab
Medical subject headings
Lymphoma, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SelicrelumabDrug

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

  • AtezolizumabDrug

    Also called Tecentriq

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

Study groups in NCT03892525
Study groupRoleWhat they receive
treatmentExperimentalNot described
Receives: Drug: Selicrelumab; Drug: Atezolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: 21 days (1 cycle)

Secondary outcomes (13)

  1. complete metabolic response rate (CMR)

    Measured: 2 months

  2. complete metabolic response rate (CMR)

    Measured: 4 months

  3. complete metabolic response rate (CMR)

    Measured: 8 months

  4. complete metabolic response rate (CMR)

    Measured: 13 months

  5. overall metabolic response rate (OMR)

    Measured: 2 months

  6. overall metabolic response rate (OMR)

    Measured: 4 months

  7. overall metabolic response rate (OMR)

    Measured: 8 months

  8. overall metabolic response rate (OMR)

    Measured: 13 months

  9. Best overall metabolic response (BOMR)

    Measured: 4 months

  10. duration of response (DOR)

    Measured: 2 years

  11. progression free survival (PFS)

    Measured: 2 years

  12. overall survival (OS)

    Measured: 2 years

  13. Number of serious adverse event (SAE)

    Measured: 16 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Mar 2019
  2. Study start4 Jul 2019
  3. Primary completion7 Apr 2021
  4. Study completion7 Apr 2021

Why it stopped: End of drug development

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03892525
Sponsor's protocol ID
ITSELF
Status last verified
Jul 2021
First submitted
26 Mar 2019
Last updated
26 Jul 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Selicrelumab and Atezolizumab in people with Recurrent B-Cell Non-Hodgkin Lymphoma and Refractory B-Cell Non-Hodgkin Lymphoma, run by The Lymphoma Academic Research Organisation at 5 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 26 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: End of drug development). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

optimal dose of intratumoral Selicrelumab in combination with flat doses of Atezolizumab IV (time frame: 21 days (1 cycle)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03892525.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2021.

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