Study of Phase I/II of the combination of L19IL2 with Rituximab in Diffuse Large B-cell Lymphoma

A Phase I/II study of the tumor-targeting human L19IL2 monoclonal antibody-cytokine fusion protein in combination with Rituximab in relapsed or refractory Diffuse Large B-cell Lymphoma (DLBCL)

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2014-001949-25-DE

Enrollment

Registered

2014-07-28

Start date

2015-04-21

Completion date

Unknown

Last updated

2023-10-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Relapsed or refractory CD20+ diffuse large B-cell lymphoma (DLBCL) in patients who are ineligible for autologous stem cell transplantation or who relapse/progress after transplantation. MedDRA version: 17.0 Level: LLT Classification code 10012907 Term: Diffuse mixed small and large cell lymphoma (Diffuse large B-cell lymphoma) recurrent System Organ Class: 100000004864 MedDRA version: 17.0 Level: LLT Classification code 10012908 Term: Diffuse mixed small and large cell lymphoma (Diffuse large

Interventions

Product Name: Darleukin Product Code: L19IL2 Pharmaceutical Form: Solution for injection INN or Proposed INN: Darleukin Current Sponsor code: L19IL2 Other descriptive name: L19 antibody fused to IL2 C

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1.Histologically confirmed CD 20-positive DLBCL 2.Patients must have experienced relapse after or did not achieve 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 3.Presence of measurable lesions according to Revised response criteria for malignant lymphoma 4.Males or females, age = 18 years 5.ECOG performance status = 2 6.Life expectancy of at least 12 weeks 7.Absolute neutrophil count > 1.5 x 10^9/L 8.Hemoglobin > 8.0 g/dL 9.Platelets > 50 x 10^9/L 10.Total bilirubin = 30 µmol/L (or = 2.0 mg/dl) 11.No abnormal electrocardiogram findings requiring treatment 12.ALT and AST = 3.0 x the upper limit of normal (ULN) (5.0 x ULN for patients with hepatic involvement with tumor) 13.Serum creatinine =65 years) yes F.1.3.1 Number of subjects for this age range 5

Exclusion criteria

Exclusion criteria: 1.Primary central nervous system lymphoma 2.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 Grade II, New York Heart Association (NYHA) criteria) 8.Uncontrolled hypertension 9.Ischemic peripheral vascular disease (Grade IIb-IV) 10.Severe diabetic retinopathy 11.Active autoimmune disease 12.History of organ allograft or stem cell transplantation 13.Recovery from major trauma including surgery within 4 weeks prior to administration of study treatment 14.Known history of allergy to IL2 or other human proteins/peptides/antibodies 15.Positive serum pregnancy test (for women of child-bearing potential only) at screening 16.Breast feeding female 17.Anti-tumor therapy within 4 weeks of the administration of study treatment (except small surgery) 18.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 criterion 19.Any conditions that in the opinion of the investigator could hamper compliance with the study protocol

Design outcomes

Primary

Measure	Time frame
Main Objective: Phase I: 1) To assess the MTD and monitor the safety of L19IL2 in combination with Rituximab in patients with relapsed or refractory DLBCL and to describe DLT. 2) To define the RD of L19IL2 to be used in phase II when administered in combination with Rituximab to patients with relapsed or refractory DLBCL. Phase II: To assess the therapeutic efficacy measured as complete remission rate and ORR of L19IL2 when administered in combination with Rituximab to patients with relapsed or refractory DLBCL. ;Secondary Objective: Phase I: 1)To assess objective responses of L19IL2 when administered in combination with Rituximab to patients with relapsed or refractory DLBCL. 2) To assess PFS and OS in patients treated within this protocol. Phase II: To assess safety of L19IL2 when administered in combination with Rituximab to patients with relapsed or refractory DLBCL. To assess PFS and OS in patients treated within this protocol. ;Primary end point(s): CR Rate ORR;Timepoint(s) of evaluation of this end point: Week 6	—

Measure

Time frame

Main Objective: Phase I: 1) To assess the MTD and monitor the safety of L19IL2 in combination with Rituximab in patients with relapsed or refractory DLBCL and to describe DLT. 2) To define the RD of L19IL2 to be used in phase II when administered in combination with Rituximab to patients with relapsed or refractory DLBCL. Phase II: To assess the therapeutic efficacy measured as complete remission rate and ORR of L19IL2 when administered in combination with Rituximab to patients with relapsed or refractory DLBCL. ;Secondary Objective: Phase I: 1)To assess objective responses of L19IL2 when administered in combination with Rituximab to patients with relapsed or refractory DLBCL. 2) To assess PFS and OS in patients treated within this protocol. Phase II: To assess safety of L19IL2 when administered in combination with Rituximab to patients with relapsed or refractory DLBCL. To assess PFS and OS in patients treated within this protocol. ;Primary end point(s): CR Rate ORR;Timepoint(s) of evaluation of this end point: Week 6

—

Secondary

Measure	Time frame
Secondary end point(s): CR Rate ORR;Timepoint(s) of evaluation of this end point: Week 6	—

Countries

Germany

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026