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)

NCT02957019 | Terminated Phase 1 DMC

• 1 other identifier: PH-L19IL2RTX-01/14
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Diffuse Large B-cell Lymphoma (DLBCL)

Outcome Measures

Primary Outcomes (2)

• 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

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

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

  From Day 38 to Day 42

Secondary Outcomes (13)

• The overall response rate (ORR) - phase I study

  Up to 24 months

• Median progression free survival (PFS) - phase I study

  Up to 24 months

• Median overall survival (OS) - phase I study

  Up to 24 months

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

  At Day 2 of Cycle 1

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

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

Study Arms (1)

L19-IL2 + RTX

EXPERIMENTAL

Phase 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.

Drug: L19-IL2 - Ph I; Drug: L19-IL2 at RD - Ph II; Drug: Rituximab

Interventions

L19-IL2 - Ph I DRUG

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 + RTX

L19-IL2 at RD - Ph II DRUG

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

L19-IL2 + RTX

Rituximab DRUG

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

L19-IL2 + RTX

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Philogen S.p.A.: lead

Study Sites (1)

Münster University Hospital

Münster, 48149, Germany

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2016
• First Posted: November 7, 2016
• Study Start: July 31, 2013
• Primary Completion: September 1, 2023
• Study Completion: September 29, 2023
• Last Updated: October 10, 2023

Record last verified: 2023-10

Locations

DE (1)