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B-cell NHLPhase 1/2NCT05869279

Allogeneic CARCIK-CD19 in Adults/Pediatric B-cell NHL or Chronic Lymphocytic Leukemia

A Phase 1/2 study testing CARCIK-CD19 in people with B-cell NHL and CLL, run by Fondazione Matilde Tettamanti Menotti De Marchi Onlus at 1 site in Italy.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This is a single arm, open-label, multi-center, phase I/II study to determine the engraftment, safety and clinical activity of allogeneic CARCIK-CD19 cells in adult and pediatric patients with relapsed/refractory mature B-cell neoplasia expected to express CD19 i.e. B-cell NHL and CLL. Read more about this study

Who is it for?
Ages 1 year and older
Conditions the study is for
B-cell NHL, CLL
What is being tested?
CARCIK-CD19
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
1 siteItaly
Study dates
1 Dec 2023to 1 Sep 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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 1 year and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • criteria apply:
  • Able and willing to provide written informed consent and to comply with the study protocol according to International Conference on Harmonization (ICH) and local regulations.
  • Ineligibility to commercially available CAR-T cells
  • Age limits: children (1-17 years old) and adults (≥18 years old)
  • Availability of an at least haploidentical (i.e. 4/8 HLA matched by allele typing) familial donor willing to and eligible for blood donation
  • Histologically-confirmed mature B-cell neoplasia (NHL), according to according to WHO 2021 classification:
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  • Eligible histologies include: indolent [follicular lymphoma (FL) or marginal zone lymphoma (MZL) nodal; extra-nodal; or splenic] or aggressive [diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBL), high-grade B cell lymphoma with MYC and BCL2 rearrangements (double-hit lymphoma), mantle cell lymphoma (MCL), including transformed B-cell NHL], CLL or lymphocytic lymphoma (LL). high-grade B cell lymphoma (HGBCL) NOS. Additional histologies including Burkitt lymphoma and Richter syndrome will be considered upon review with Sponsor.
  • Relapsed after or refractory to at least two prior lines of treatment, and no available treatment options that are expected to prolong survival (e.g. chemotherapy or high-dose chemotherapy/stem cell transplantation, commercially available CART cell therapy or other standard treatment) or patients refusing such treatments
  • At least one measurable target lesion, measurable as defined by Lugano 2014 classification (nodal: > 1.5 cm longest transverse diameter; extra-nodal: > 1 cm longest transverse diameter) by computerized tomography (CT) scan or presence of assessable disease (i.e. bone marrow or spleen)
  • Eastern Cooperative Oncology Group (ECOG) performance status equal to 2 or less for subject ≥ 16 years of age, or Lansky >50 for subjects < 16 years of age
  • Adequate cardiac and pulmonary function: ejection fraction (EF) by echo or MUGA >40% and radial artery (RA) oxygen saturation >92%.
  • Life expectancy (in the opinion of the Investigator) of > 12 weeks
  • Adequate liver function:
  • Total bilirubin ≤ 2.0x ULN (≤ 3x ULN in patients with Gilbert's syndrome or documented liver involvement)
  • AST (aspartate aminotransferase) /ALT (alanine aminotransferase) 3x ULN or 5x for patients with evidence of liver involvement with lymphoma
  • Adequate bone marrow function to receive lymphodepleting chemotherapy at investigator judgment.
  • Adequate renal function: creatinine ≤1.5x ULN or creatinine clearance (CrCl) calculated by Cockcroft-Gault formula of ≥50 mL/min for adult patients in whom, in the Investigator's judgment, serum creatinine levels do not adequately reflect renal function. For children, CrCl will be calculated by local institutional standard.
  • Females of childbearing potential (FCBP) subjects must:
  • Have a negative pregnancy test as verified by the local investigator
  • Either commit to true abstinence from heterosexual contact or agree to use, and be able to comply with, effective contraception without interruption from screening until at least 12 months following CARCIK-CD19 infusion and until CAR positive viable T cells are no longer present by quantitative polymerase chain reaction (qPCR) on two consecutive tests.
  • Contraception methods must include one highly effective method including: surgical female sterilization, use of oral (estrogen and progesterone), injected, or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate <1%)
  • Agree to abstain from breastfeeding during study participation and for at least 12 months following CARCIK-CD19 infusion and until CAR positive viable T cells are no longer present by quantitative polymerase chain reaction (qPCR) on two consecutive tests.
  • Male subjects must:
  • Practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential for 12 months after following CARCIK-CD19 infusion and until CAR positive viable T cells are no longer present by quantitative polymerase chain reaction (qPCR) on two consecutive tests.

Who cannot join

  • Patients with clinically significant active viral, bacterial or fungal infection or any major episode of infection requiring hospitalization or treatment with IV antibiotics (for IV antibiotics this pertains to completion of last course of antibiotic treatment) within 2 weeks prior to CARCIK-CD19 infusion.
  • Patients with an active infection with Hepatitis B. However, patients with a controlled (treated) hepatitis will be allowed if the all the following criteria are met:
  • Anti-viral therapy for hepatitis B virus (HBV) must be given for at least 1 month prior to time of informed consent;
  • HBV viral load must be <2000 IU/mL (104 copies/mL) prior to time of informed consent; and
  • those on active HBV therapy with viral load <2000 IU/mL (104 copies/mL) should stay on the same anti-viral therapy throughout study treatment
  • Patients with an active hepatitis C virus (HCV) infection. However, patients with successfully treated chronic HCV infection will be allowed if they show a sustained virologic response at 12 weeks (SVR12) or 24 weeks (SVR24), and if there is a 4-week period between achieving sustained viral response (SVR12 or SVR24) and time of informed consent.
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  • Patients with a positive serologic test or a positive molecular PCR test for human immunodeficiency virus (HIV) are eligible if asymptomatic, well controlled by the HAART therapy and no medically significant active infection is present
  • Rapidly progressive disease that in the estimation of the investigator and sponsor could affect compliance with the protocol or interpretation of results
  • Active CNS lymphoma
  • Major surgery or significant traumatic injury 28 days prior to CARCIK-CD19 infusion (excluding biopsies) or anticipation of the need for major surgery during study treatment
  • Patients with another active invasive malignancy with a life expectancy of less than 3 years
  • Significant cardiovascular disease (such as New York Heart Association (NYHA) Class II cardiac disease, congestive heart failure, myocardial infarction or cerebrovascular accident within 30 days prior to CARCIK-CD19 infusion, unstable arrhythmias, or unstable angina)
  • Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including diabetes mellitus, history of relevant pulmonary disorders (bronchospasm, obstructive pulmonary disease) and known autoimmune diseases
  • Treatment with any other standard anti-cancer radiotherapy / chemotherapy including investigational therapy (defined as treatment for which there is currently no regulatory authority approved indication) within 2 weeks prior to CARCIK-CD19 infusion
  • Allogeneic or autologous Stem Cell Transplantation within 3 months prior to CARCIK-CD19 infusion, or Donor Lymphocytes (DLI)
  • Active GvHD Grades II-IV or extensive chronic Graft-versus-Host Disease (for patients who had previously been allotransplanted)
  • Prior treatment with CART cell therapy within 30 days before first study treatment administration (lymphodepletion)
  • Toxicities from prior anti-cancer therapy including immunotherapy that did not resolve to ≤ Grade 1 with the exception of alopecia, endocrinopathy managed with replacement therapy and stable vitiligo.
  • Ongoing corticosteroid use 25 mg/day (> or 0.3 mg/kg for children) of prednisone or equivalent within 1 weeks prior to CARCIK-CD19 infusion
  • Administration of a live, attenuated vaccine within 4 weeks prior to CARCIK-CD19 infusion

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Andrea Biondi, MD contact

+39039233 ext. 6816

segreteriadirezionecp@fondazionembbm.it

Alessandro Rambaldi, MD contact

+39035267 ext. 3684

ematologiasegr@asst-pg23.it

Italy1 site, 1 recruiting

  • Ospedale Papa Giovanni XXIII

    Bergamo, BG, 24127

    Alessandro Rambaldi, MD, alessandro.rambaldi@unimi.it

    Federico Lussana, MD, flussana@asst-pg23.it

    Recruiting

Other trials in Italy

About this study

Official title: Phase I/II Trial to Determine the in Vivo Engraftment, Safety and Clinical Activity of Allogeneic CIK Cells Transduced With a Transposon CD19-chimeric Antigen Receptor (CARCIK-CD19) Gene in Adult and Pediatric Patients With Relapsed/Refractory B-cell Non-Hodgkin Lymphoma

This is a single arm, open-label, multi-center, phase I/II study to determine the engraftment, safety and clinical activity of allogeneic CARCIK-CD19 cells in adult and pediatric patients with relapsed/refractory mature B-cell neoplasia expected to express CD19 i.e. B-cell NHL and CLL.

CARCIK-CD19 will be produced from the peripheral blood of an at least haploidentical familial donor.

Conditions
B-cell NHL, CLL
Being tested
CARCIK-CD19

What participants receive

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

  • CARCIK-CD19Biological

    allogeneic cytokine induced killer cells transduced with a transposon CD19-chimeric antigen receptor (CARCIK-CD19) gene

Study groups in NCT05869279
Study groupRoleWhat they receive
CARCIK-CD19ExperimentalGene therapy product composed of T lymphocytes differentiated according CIK-cell protocol (leading to production of CD3+ cells also expressing CD8 and to a lesser extent CD4 or CD56) that have been genetically modified to express CAR with specificity for targeting CD19 molecule expressed on the surface of B cells. The CARCIK-CD19 contains cells that express the anti-CD19 single chain fragment variable (scFV) linked to an intracellular signaling domain comprising the TCR CD3 ζ chain and tandem costimulatory domains as the CD28 and OX40 (CD19-CD28OX40).
Receives: Biological: CARCIK-CD19

What is being measured

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

  1. Dose Limiting Toxicity

    Dose Limiting Toxicity

    Measured: 28 day after CARCIK infusion

  2. overall response rate

    overall response rate (complete + partial remission)

    Measured: month 3 after CARCIK-CD19 infusion

Secondary outcomes (1)

  1. Adverse event (AE)

    Incidence of Adverse event

    Measured: up to 12 months

Timeline

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

  1. First posted22 May 2023
  2. Study start1 Dec 2023
  3. Primary completion1 Sep 2026 (estimated)
  4. Study completion1 Sep 2027 (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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
29 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05869279
Sponsor's protocol ID
FT04CARCIK
Status last verified
May 2023
First submitted
3 May 2023
Last updated
3 May 2024
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 1/2 study testing CARCIK-CD19 in people with B-cell NHL and CLL, run by Fondazione Matilde Tettamanti Menotti De Marchi Onlus at 1 site in Italy.

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 24 inclusion and 20 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: looking for participants now, as of the sponsor's last update on 3 May 2024. 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 Italy. 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 combined 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.

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?

This study is still under way. Results are not available in the source record yet.

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

Contact Andrea Biondi, MD (+39039233 ext. 6816, segreteriadirezionecp@fondazionembbm.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Limiting Toxicity (time frame: 28 day after CARCIK infusion). The study lists 2 primary outcomes in all. 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 NCT05869279.

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 3 May 2024.

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