- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02957019
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)
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Münster, Germany, 48149
- Münster University Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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
- 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
Exclusion Criteria:
- 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
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: L19-IL2 + RTX
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. |
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
Patients will receive L19-IL2 at the RD defined during the Phase I part of the study
Patients will receive a fixed dose of Rituximab (375 mg/m2) per administration during Phase I and Phase II of the study
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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)
|
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
Time Frame: From Day 38 to Day 42
|
From Day 38 to Day 42
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
The overall response rate (ORR) - phase I study
Time Frame: Up to 24 months
|
Up to 24 months
|
Median progression free survival (PFS) - phase I study
Time Frame: Up to 24 months
|
Up to 24 months
|
Median overall survival (OS) - phase I study
Time Frame: Up to 24 months
|
Up to 24 months
|
Pharmacokinetics assessment of L19-IL2 through blood sampling - phase I study
Time Frame: At Day 2 of Cycle 1
|
At Day 2 of Cycle 1
|
Human anti-fusion protein antibodies (HAFA) levels - phase I study
Time Frame: (1) at Day 2, (2) at Day 23, (3) from Day 38 to Day 42, (4) from Day 80 to Day 84
|
(1) at Day 2, (2) at Day 23, (3) from Day 38 to Day 42, (4) from Day 80 to Day 84
|
Percentage of Participants With On-Study Adverse Events (AEs) and Serious Adverse Events (SAEs) - phase II study
Time Frame: Up to 24 months
|
Up to 24 months
|
Percentage of Participants With Worst On-Study Hematological and Chemistry Abnormalities - phase II study
Time Frame: Up to 24 months
|
Up to 24 months
|
Number of Patients With Abnormal Physical Examinations - phase II study
Time Frame: Up to 24 months
|
Up to 24 months
|
Relative percentage difference in vital signs from baseline - phase II study
Time Frame: Up to 24 months
|
Up to 24 months
|
The overall response rate (ORR) - phase II study
Time Frame: Up to 24 months
|
Up to 24 months
|
Median progression free survival (PFS) - phase II study
Time Frame: Up to 24 months
|
Up to 24 months
|
Median overall survival (OS) - phase II study
Time Frame: Up to 24 months
|
Up to 24 months
|
Human anti-fusion protein antibodies (HAFA) levels - phase II study
Time Frame: (1) at Day 2, (2) at Day 23, (3) from Day 38 to Day 42, (4) from Day 80 to Day 84
|
(1) at Day 2, (2) at Day 23, (3) from Day 38 to Day 42, (4) from Day 80 to Day 84
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma, Non-Hodgkin
- Lymphoma
- Lymphoma, B-Cell
- Lymphoma, Large B-Cell, Diffuse
- Physiological Effects of Drugs
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Analgesics, Non-Narcotic
- Antirheumatic Agents
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Rituximab
- Interleukin-2
Other Study ID Numbers
- PH-L19IL2RTX-01/14
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Diffuse Large B-cell Lymphoma (DLBCL)
-
Memorial Sloan Kettering Cancer CenterSanofi; Columbia University; Medical College of Wisconsin; University of Rochester and other collaboratorsActive, not recruitingDiffuse Large B-cell Lymphoma (DLBCL) | Relapsed Diffuse Large B-cell Lymphoma (DLBCL) | Refractory Diffuse Large B-cell Lymphoma (DLBCL)United States
-
University Health Network, TorontoNot yet recruitingDiffuse Large B Cell Lymphoma (DLBCL)Canada
-
Hoffmann-La RocheRecruitingDiffuse Large B-Cell Lymphoma (DLBCL)United States
-
2seventy bioRecruitingDiffuse Large B Cell Lymphoma (DLBCL)United States
-
AmgenMerck Sharp & Dohme LLCCompletedRelapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL)United States, Germany, Spain, Australia, Netherlands, France
-
Fondazione Italiana Linfomi ONLUSCompletedDiffuse Large B Cell Lymphoma (DLBCL) | Elderly Patients (>65 Years)Italy
-
Arbeitsgemeinschaft medikamentoese TumortherapieHoffmann-La RocheCompletedDiffuse Large B-Cell Lymphoma (DLBCL) | Follicular NHL Grade 3bHong Kong, Thailand, Sweden, Taiwan, Mexico, Austria, Serbia, China, Czech Republic, Australia, Malaysia, Croatia, Israel, South Africa, Bosnia and Herzegovina, Brazil, Bulgaria, Estonia, Latvia, Macedonia, The Former Yugoslav... and more
-
Fondazione Italiana Linfomi - ETSNot yet recruitingClassical Hodgkin Lymphoma | Primary Mediastinal Large B-cell Lymphoma (PMBCL) | Diffuse Large B Cell Lymphoma (DLBCL)Italy
-
Memorial Sloan Kettering Cancer CenterActinium PharmaceuticalsRecruitingDiffuse Large B-cell Lymphoma | B-ALL | DLBCL | DLBCL, Nos Genetic Subtypes | B ALL | Dlbcl-Ci | DLBCL Unclassifiable | DLBCL Activated B-Cell Type | DLBCL Germinal Center B-Cell Type | HGBL | HGBL, NosUnited States
-
Memorial Sloan Kettering Cancer CenterRecruitingLymphoma | Lymphoma, B-Cell | DLBCL - Diffuse Large B Cell Lymphoma | Large B-cell Lymphoma | Large-cell Lymphoma | Mediastinal B-Cell Diffuse Large Cell LymphomaUnited States
Clinical Trials on L19-IL2 - Ph I
-
Maastricht Radiation OncologyCompleted
-
Maastricht Radiation OncologyKarolinska Institutet; KU Leuven; Maastricht University Medical Center; Catholic... and other collaboratorsWithdrawnNSCLC Stage IV | Limited Metastatic DiseaseNetherlands
-
Maastricht University Medical CenterKU Leuven; University College, London; Erasmus Medical Center; Catholic University... and other collaboratorsRecruitingNSCLC Stage IV | Metastatic DiseaseBelgium, Netherlands, United Kingdom, France, Germany, Italy
-
Philogen S.p.A.Active, not recruiting
-
National Cancer Institute (NCI)Not yet recruitingAdvanced Malignant Solid Neoplasm | Metastatic Malignant Solid Neoplasm
-
Cukurova UniversityCompleted
-
Fudan UniversityRecruitingDepression, Anxiety | PCOS (Polycystic Ovary Syndrome) of Bilateral OvariesChina
-
Genentech, Inc.CompletedAdvanced Unresectable or Metastatic Solid MalignancyUnited States