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B Cell LymphomaPhase 2NCT05385263

Addition of Nivolumab to Anti-CD-19 CAR-T Cells in Patients With Stable/Progressive DLBCL at Lymphodepletion

A Phase 2 study testing Nivolumab Injection [Opdivo] in people with B Cell Lymphoma, run by Tel-Aviv Sourasky Medical Center at 1 site in Israel.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Progression of DLBCL is the major obstacle for the success of chimeric antigen receptor-T cell (CAR-T) with approximately 60% of the patients relapsing in the first year, and 40% within 3 months, after infusion. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
B Cell Lymphoma
What is being tested?
Nivolumab Injection [Opdivo]
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteIsrael
Study dates
11 May 2022to Oct 2024
Phase
Phase 2
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

  • Participant must be at least 18 years of age inclusive, at the time of signing the informed consent.
  • DLBCL treated with CAR-T targeting CD19 (tisagenlecleucel, axicabtagene ciloleucel, or lisocabtagene maraleucel)
  • PD/SD by PET-CT on the day of lymphodepletion
  • Capable of giving signed informed consent
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • No active CRS or ICANS at time of nivolumab administration

Who cannot join

  • Hypersensitivity to checkpoints inhibitors
  • CRS grade 3 and above or ICANS any grade on days 0-5 following CAR-T
  • AST (Aspartate transaminase) or ALT (Alanine transaminase) over 3 times the upper limit of normal (ULN) or total bilirubin over 3 times ULN
  • Serum creatinine over 1.5 times ULN or over 1.5 times baseline
  • History of or active autoimmune disease
  • Uncontrolled seizure activity and/or clinically evident progressive encephalopathy
Show all 12Show fewer
  • Active diarrhea (more than 4 bowel movements per day)
  • Clinically significant uncontrolled illness
  • Active infection requiring antibiotics
  • Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection
  • Other active malignancy
  • Females only: Pregnant or breastfeeding

Trial locations and contacts

1 site in 1 country.

Ron Ram, Prof contact

972-3-6947830 ext. 7830

ronr@tlvmc.gov.il

Israel1 site, 1 recruiting

  • Tel-Aviv Sourasky Medicak center / BMT Unit

    Tel Aviv, 6423906

    Ron Ram, MD, +972-3-6974138, ronr@tlvmc.gov.il

    Recruiting

Other trials in Israel

About this study

Official title: Addition of Nivolumab to Standard of Care With Anti-CD-19 CAR-T Cells in Patients With Stable/Progressive DLBCL at Lymphodepletion

Progression of DLBCL is the major obstacle for the success of chimeric antigen receptor-T cell (CAR-T) with approximately 60% of the patients relapsing in the first year, and 40% within 3 months, after infusion. While patient with DLBCL in Partial Response/Complete Response at lymphodepletion have a 1-year Progression Free Survival (PFS) of 60-80%, those with Stable Disease/Progressive Disease at time of lymphodepletion have a dismal PFS of 20-30%.

Trials showed that better expansion of CAR-T cells, even in patients with a progressive disease, may overcome this grave prognosis and may result in better PFS

Read the detailed description

Factors that may introduce resistance to CAR-T. in addition to the bulk of disease, include also expression of check point molecules that eventually interfere with the CAR-T action. The investigator, have recently shown (EBMT 2022, # LWP-03) a real-life data, that day +7 CAR-T concentration in patients with stable or progressive disease (SD/PD) at lymphodepletion segregates patients to those with high CAR-T blood concentrations that achieve a high CR/PR rate after CAR-T infusion ,those with 20-100 CAR-T cells/microL that achieve a lower CR/PR rate after CAR-T infusion, and those with <20 cells/microL that achieve the lowest CR/PR rate after infusion. Thus, the extent of CAR-T cell expansion on day 7 after treatment is a prognostic marker predicting response to treatment in this patient group. Considering all these - patients with SD/PD at time of lymphodepletion, and specifically those with lower CAR-T blood concentrations on day +7 are at a very high risk for early disease progression after CAR-T infusion and, as such, there is an urgent unmet medical need to improve their outcomes.

Addition of anti PD-1 to patients with low expansion of CAR-T cells may overcome the inhibitory effect of PD-1 expression and may result in a better function of the CAR-T and eventually tumor suppression.

Nivolumab is a human monoclonal antibody targeting (programmed death-1 ) PD-1, a negative regulatory molecule expressed by activated T and B lymphocytes. Anti PD-1 treatment has been administered as a single dose or repeated administration in different time points during CAR-T cell therapy. These studies showed that this treatment is safe, well tolerated and does not result in increased CAR-T associated toxicities, mainly cytokine release syndrome(CRS) and immune effector cell associated neurotoxicity(ICANS). The optimal time window to administer these agents for achieving safety and efficacy is not determined.

Conditions
B Cell Lymphoma
Being tested
Nivolumab Injection [Opdivo]
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.

  • Nivolumab Injection [Opdivo]Drug

    Nivolumab ( 3mg/kg IV) on day +5. If CAR-T expansion<100 cells/microL on day +7 one additional dose of nivolumab (3mg/kg IV) will be given on day +19

Study groups in NCT05385263
Study groupRoleWhat they receive
NIVOLUMABExperimentalAll patients enrolled will be given nivolumab ( 3mg/kg IV) on day +5 Patients with CAR-T expansion<100 cells/microL on day +7 will be given 1 additional dose of nivolumab (3mg/kg IV) on day +19 (two weeks after first dose of nivolumab).
Receives: Drug: Nivolumab Injection [Opdivo]

What is being measured

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

  1. Overall response at 1 months after CAR-T infusion

    Complete or partial remission rate assessed by PET-CT (Positron Emission Tomography ) at 1 month after combination therapy with nivolumab and CAR-T.

    Measured: One month post CAR-T infusion

Secondary outcomes (5)

  1. Overall survival at 1 year after CAR-T infusion and nivolumab

    To assess survival of patients at 1 year after infusion of CAR-T and addition of nivolumab.

    Measured: One year post CAR-T infusion

  2. Duration of response

    Assess duration of disease response after CAR-T infusion

    Measured: One year post CAR-T infusion

  3. Cytokine release syndrome

    Assesment of cytokine release syndrome according to the American Society for Transplantation and Cellular Therapy (ASTCT) grading system (grade 0-4, 4 being the worse) (TCT. 2019 Apr; 25(4);625-638)

    Measured: One year post CAR-T infusion

  4. Neurotoxicity

    Assesment of neurotoxicity according to the American Society for Transplantation and Cellular Therapy (ASTCT) grading system (grade 0-4, 4 being the worse) (TCT. 2019 Apr; 25(4);625-638)

    Measured: One year post CAR-T infusion

  5. Hemophagocytic lymphohistiocytosis (HLH)

    Assesment of HLH according to the Common Terminology Criteria for Adverse Events CTCAE (version 5.0) (grade 3-5, 5 being the worse)

    Measured: One year post CAR-T infusion

Timeline

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

  1. First posted23 May 2022
  2. Study start11 May 2022
  3. Primary completionApr 2024 (estimated)
  4. Study completionOct 2024 (estimated)

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
All patients enrolled to this study with DLBCL in SD/PD at time of lymphodepletion will be given nivolumab ( 3mg/kg IV) on day +5 Patients with CAR-T expansion\<100 cells/microL on day +7 will be given 1 additional dose of nivolumab (3mg/kg IV) on day +19 (two weeks after first dose of nivolumab).
Masking
None (open label)
Enrolment
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05385263
Sponsor's protocol ID
0804-21
Status last verified
Apr 2022
First submitted
13 Apr 2022
Last updated
26 May 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Ram R, Amit O, Perry C, Herishanu Y, Avivi I, Sarid N, Apel A, Preis M, Aviv A, Shapira S, Shragai T, Joffe E, Shargian L, Herzog-Tsarfati K, Eylati N, Acria L, Fridberg G, Gold R, Glait-Santar C, Kay S, Gal-Rabinovich K, Rosenberg D, Setter-Marco N, Beyar-Katz O. Addition of Nivolumab Tailored by Expansion of CAR-T Cells in Patients with Stable/Progressive Large B Cell Lymphoma at Lymphodepletion-A Phase 2, Prospective Interventional Study. Transplant Cell Ther. 2024 Dec;30(12):1178-1188. doi: 10.1016/j.jtct.2024.09.024. Epub 2024 Oct 11.

    PubMed 39396632

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab Injection [Opdivo] in people with B Cell Lymphoma, run by Tel-Aviv Sourasky Medical Center at 1 site in Israel.

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 6 inclusion and 12 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: status not confirmed, as of the sponsor's last update on 26 May 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Israel. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Results are not available in the source record.

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

Contact Ron Ram, Prof (972-3-6947830 ext. 7830, ronr@tlvmc.gov.il), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall response at 1 months after CAR-T infusion (time frame: One month post CAR-T infusion). 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 NCT05385263, which also lists 1 linked publication.

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 May 2022.

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