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Diffuse Large B-cell Lymphoma (DLBCL)Phase 1/2NCT02957019

A Phase I/II Study of the Tumor-targeting Human L19-IL2 Monoclonal Antibody-cytokine Fusion Protein in Combination With Rituximab in Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)

A Phase 1/2 study testing L19-IL2 - Ph I, L19-IL2 at RD - Ph II and Rituximab in people with Diffuse Large B-cell Lymphoma (DLBCL), run by Philogen S.p.A. at 1 site in Germany.

Terminated

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

Official record
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Trial summary

Phase I/II, open-label, multicenter, prospective study. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Diffuse Large B-cell Lymphoma (DLBCL)
What is being tested?
L19-IL2 - Ph I, L19-IL2 at RD - Ph II and Rituximab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteGermany
Study dates
31 Jul 2013to 29 Sep 2023
Phase
Phase 1/2
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

  • Histologically confirmed CD 20-positive DLBCL
  • Patients must have experienced relapse after or not have achieved CR with standard R-CHOP-like treatment and must be ineligible for autologous stem cell transplantation or must have relapsed/progressed after autologous or allogeneic stem cell transplantation. In this last case, time lapse between autologous stem cell transplantation and beginning of L19-IL2 treatment must not be less than 4 weeks; in case of allogeneic stem cell transplantation, L19-IL2 treatment can start 4 weeks after removal of immunosuppressive drug(s).
  • Presence of measurable lesions according to Revised response criteria for malignant lymphoma
  • Males or females, age ≥ 18 years
  • ECOG performance status ≤ 2
  • Life expectancy of at least 12 weeks
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  • Absolute neutrophil count > 1.5 x 109/L
  • Hemoglobin > 8.0 g/dL
  • Platelets > 50 x 109/L
  • Total bilirubin ≤ 30 µmol/L (or ≤ 2.0 mg/dl)
  • No abnormal electrocardiogram findings requiring treatment
  • ALT and AST ≤ 3.0 x the upper limit of normal range (ULN) (5.0 x ULN for patients with hepatic involvement with lymphoma)
  • Serum creatinine < 2 x ULN
  • Negative tuberculosis test (e.g. Quantiferon-assay)
  • All acute toxic effects (excluding alopecia) of any prior therapy must have resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (v4.03) Grade ≤ 1 unless otherwise specified above
  • Negative serum pregnancy test (for women of child-bearing potential only) at screening
  • If of childbearing potential, agreement to use adequate contraceptive methods (e.g., oral contraceptives, condoms, or other adequate barrier controls, intrauterine contraceptive devices, or sterilization) beginning at the screening visit and continuing until 3 months following last treatment with study drug
  • Able to provide written Informed Consent
  • Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures

Who cannot join

  • Evidence of central nervous system lymphoma
  • Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (TA, Tis \& Ti) or any cancer curatively treated < 5 years prior to study entry
  • Hypersensitivity to Rituximab or to murine proteins, or to any of its excipients (Sodium citrate, Polysorbate 80, Sodium chloride, Sodium hydroxide, Hydrochloric acid)
  • History of HIV infection or infectious hepatitis B or C
  • Presence of active, severe infections (e.g., tuberculosis, sepsis and opportunistic infections or any infection requiring antimicrobial therapy) or other severe concurrent disease, which, in the opinion of the investigator, would place the patient at undue risk or interfere with the study. Patients with a history of recurring or chronic infections or with underlying conditions which may further predispose them to serious infections should be excluded from the study.
  • Active graft-versus-host disease in patients with a history of allogeneic stem cell transplantation
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  • History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris
  • Inadequately controlled cardiac arrhythmias including atrial fibrillation
  • Heart insufficiency (> Grade II, New York Heart Association (NYHA) criteria)
  • Uncontrolled hypertension
  • Ischemic peripheral vascular disease (Grade IIb-IV)
  • Severe diabetic retinopathy
  • Active autoimmune disease
  • History of solid organ allograft
  • Recovery from major trauma including surgery within 4 weeks prior to administration of study treatment
  • Known history of allergy to IL2 or other human proteins/peptides/antibodies
  • Positive serum pregnancy test (for women of child-bearing potential only) at screening
  • Breast feeding female
  • Anti-tumor therapy within 4 weeks of the administration of study treatment (except small surgery)
  • Patient requires or is taking corticosteroids or other immunosuppressant drugs on a long-term basis. Limited use of corticosteroids to treat or prevent acute hypersensitivity reactions is not considered an exclusion criterionAny conditions that in the opinion of the investigator could hamper compliance with the study protocol

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • Münster University Hospital

    Münster, 48149

Other trials in Germany

About this study

Phase I/II, open-label, multicenter, prospective study.

Read the detailed description

Phase I - Dose definition: A prospective, open-label, multi-center Phase I dose escalation study in which cohorts of 3-6 patients will receive escalating doses of L19-IL2 in combination with a fixed dose of Rituximab (375 mg/m2).

Phase II - Activity Evaluation: Open-label, multi-center, prospective study during which 14 enrolled patients will receive a fixed dose of Rituximab (375 mg/m2) in combination with L19-IL2 at the RD defined during the Phase I part of the study.

The study is designed to establish whether L19-IL2, administered in combination with Rituximab is well tolerated and can achieve objective responses and clinical benefit to patients with relapsed or refractory DLBCL.

Being tested
L19-IL2 - Ph I, L19-IL2 at RD - Ph II, Rituximab
Medical subject headings
Lymphoma, Large B-Cell, Diffuse

What participants receive

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

  • L19-IL2 - Ph IDrug

    Patients will receive increasing doses of L19-IL2 (0.32, 0.43, 0.57 and 0.76 Mio IU/kg of IL-2 equivalents per administration) during Phase I study

  • L19-IL2 at RD - Ph IIDrug

    Patients will receive L19-IL2 at the RD defined during the Phase I part of the study

  • RituximabDrug

    Patients will receive a fixed dose of Rituximab (375 mg/m2) per administration during Phase I and Phase II of the study

Study groups in NCT02957019
Study groupRoleWhat they receive
L19-IL2 + RTXExperimentalPhase I (Dose definition): Cohorts of 3-6 patients will receive Rituximab on day 1 and 8 of the first 3-weeks cycle (C1D1 and C1D8, respectively) and on day 1 of the second 3-weeks cycle (C2D1). During two uninterrupted 3-weeks cycles, L19-IL2 will be administered on C1D1, C1D8, C1D15 and C2D1, C2D8, C2D15. Phase II (Activity Evaluation): During Phase II, 14 patients will receive Rituximab on C1D1 and C1D8 and on C2D1. Two uninterrupted 3-weeks cycles of L19-IL2 at the RD determined during Phase I will be administered on C1D1, C1D8 and C1D15 and C2D1, C2D8 and C2D15.
Receives: Drug: L19-IL2 - Ph I; Drug: L19-IL2 at RD - Ph II; Drug: Rituximab

What is being measured

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

  1. Number of patients with adverse events that are related to treatment and classified as DLTs for each administered dosage - phase I study

    To assess the dose limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended dose (RD) of L19-IL2 in combination with Rituximab

    Measured: Up to Day 21 of the Cycle 1 (cycle of 21 days)

  2. The rate of patients with complete response CR after 2 cycles of treatment - phase II study

    Measured: From Day 38 to Day 42

Secondary outcomes (13)

  1. The overall response rate (ORR) - phase I study

    Measured: Up to 24 months

  2. Median progression free survival (PFS) - phase I study

    Measured: Up to 24 months

  3. Median overall survival (OS) - phase I study

    Measured: Up to 24 months

  4. Pharmacokinetics assessment of L19-IL2 through blood sampling - phase I study

    Measured: At Day 2 of Cycle 1

  5. Human anti-fusion protein antibodies (HAFA) levels - phase I study

    Measured: (1) at Day 2, (2) at Day 23, (3) from Day 38 to Day 42, (4) from Day 80 to Day 84

  6. Percentage of Participants With On-Study Adverse Events (AEs) and Serious Adverse Events (SAEs) - phase II study

    Measured: Up to 24 months

  7. Percentage of Participants With Worst On-Study Hematological and Chemistry Abnormalities - phase II study

    Measured: Up to 24 months

  8. Number of Patients With Abnormal Physical Examinations - phase II study

    Measured: Up to 24 months

  9. Relative percentage difference in vital signs from baseline - phase II study

    Measured: Up to 24 months

  10. The overall response rate (ORR) - phase II study

    Measured: Up to 24 months

  11. Median progression free survival (PFS) - phase II study

    Measured: Up to 24 months

  12. Median overall survival (OS) - phase II study

    Measured: Up to 24 months

  13. Human anti-fusion protein antibodies (HAFA) levels - phase II study

    Measured: (1) at Day 2, (2) at Day 23, (3) from Day 38 to Day 42, (4) from Day 80 to Day 84

Timeline

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

  1. First posted7 Nov 2016 (estimated)
  2. Study start31 Jul 2013
  3. Primary completionSep 2023
  4. Study completion29 Sep 2023

Why it stopped: Slow progression due to difficulties in finding eligible patients. Competitive clinical trials with innovative agents and new approved products leaddefinitive stop.

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
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02957019
Sponsor's protocol ID
PH-L19IL2RTX-01/14
Status last verified
Oct 2023
First submitted
27 Oct 2016
Last updated
10 Oct 2023
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing L19-IL2 - Ph I, L19-IL2 at RD - Ph II and Rituximab in people with Diffuse Large B-cell Lymphoma (DLBCL), run by Philogen S.p.A. at 1 site in Germany.

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 19 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: stopped early, as of the sponsor's last update on 10 Oct 2023. 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 Germany. 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?

The study was stopped early (reason given: Slow progression due to difficulties in finding eligible patients. Competitive clinical trials with innovative agents and new approved products leaddefinitive stop.). 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?

Number of patients with adverse events that are related to treatment and classified as DLTs for each administered dosage - phase I study (time frame: Up to Day 21 of the Cycle 1 (cycle of 21 days)). 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 NCT02957019.

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 10 Oct 2023.

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