A clinical study to explore the efficacy and tolerability of Debio 1562 taken together with Rituximab in patients with diffuse large B-cell lymphoma (DLBCL) or other forms of non-Hodgkin's lymphoma (NHL) who have stopped responding or have failed to respond to current cancer treatments
- Conditions
- Patients with Relapsed and/or Refractory Diffuse Large B-Cell Lymphoma and Other Forms of Non-Hodgkin’s LymphomaMedDRA version: 21.0Level: PTClassification code 10012821Term: Diffuse large B-cell lymphoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 23.0Level: PTClassification code 10029601Term: Non-Hodgkin's lymphoma refractorySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 23.0Level: PTClassification code 10029600Term: Non-Hodgkin's lymphoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: PTClassification code 10012822Term: Diffuse large B-cell lymphoma refractorySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10076596Term: Marginal zone lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: LLTClassification code 10067070Term: Follicular B-cell non-Hodgkin's lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: PTClassification code 10026801Term: Mantle cell lymphoma refractorySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: PTClassification code 10026800Term: Mantle cell lymphoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-004061-87-BG
- Lead Sponsor
- Debiopharm International S.A.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 75
1) For Part 1 of the study, patients must have histopathologically confirmed diagnosis of relapsed and/or refractory DLBCL, FL, MZL/MALT, MCL, or other Sponsor approved NHL subtypes according to the World Health Organization (WHO) classification 2008 for which standard measures do not exist or are no longer effective.
2) For Part 2 and Part 3 of the study, patients must have histopathologically and clinically confirmed diagnosis of relapsed DLBCL. Patients will be considered to have a relapsed disease if they showed a duration of response of at least 24 weeks after their first line of therapy. The following patients with relapsed DLBCL will be enrolled:
i. Patients who received only one line of previous therapy and achieved either complete response (CR) or partial response (PR) for at least 24 weeks (from the last day of the last cycle) after their first line of therapy, but whom are not eligible for high dose chemotherapy with autologous stem cell transplantation (HD-ASCT)
ii. Patients who received more than one line of previous therapy (including HD-ASCT), and have achieved a duration of response (CR or PR) of at least 8 weeks (from the last day of the last cycle) after their last line of therapy
3) Patients must have received no more than six prior treatment regimens. Prior treatment with an anti- CD20 agent, either alone or in combination, is allowed.
4) Patients must be = 18 years.
5) Patients must have ECOG Performance Status 0-2.
6) Patients must meet the following laboratory criteria:
- Absolute neutrophil count (ANC) = 1.0 x 10^9/L (1000/mm^3),
- Platelet count = 50 x 10^9/L (50,000/mm^3; patients must not have been transfused within 10 days previous blood drawn for laboratory assessment),
-Patients receiving therapeutic anticoagulation are eligible provided their anticoagulation parameters are within range (e.g. International Normalized Ratio [INR] 2-3 on Coumadin if applicable) and they have no history of = Grade 2 bleeding while on anticoagulatioin therapy.
-For patients receiving therapeutic doses of anticoagulation: Platelet count = 100 x 10^9/L (100,000/mm^3; must not have been transfused wihtin previous 10 days)
- Hemoglobin = 8.0 g/dL (may have been transfused),
- Serum creatinine = 2.0 x upper limit of normal (ULN) or 24-hour creatinine clearance of = 60 mL/minute,
- AST = 2.5 x ULN; ALT = 2.5 x ULN and
- Total bilirubin = 1.5 x ULN; patients with documented diagnosis of Gilbert syndrome are eligible if total bilirubin = 3.0 x ULN.
7) Patients must have evaluable or measurable disease in accordance with the International Working Group Guidelines for Lymphoma (Cheson 2014).
8) Patients who are Hepatitis B surface antygen (HBsAg) + (must be PCR negative) who are taking antivirals are allowed to enroll.
9) Male patients and female patients of child bearing potential participating in the study must agree to use two highly effective methods of contraception throughout this study and for at least 12 weeks after the last dose of Debio 1562 and 12 months after the last dose of rituximab. Examples of acceptable birth control methods include but are not limited to the following methods: (e.g, oral, parenteral, or implantable hormonal contraceptive; tubal ligation; intra-utérine device; barrier contraceptive with spermicide; partner's latex condom or vasectomy).
10) Patients must be willing and able to sign the informed consent form and comply with the study protocol.
11) Patients must have available a pathol
1) Patients with a diagnosis of CLL or Small Lymphocytic Lymphoma.
2) For Part 2 and Part 3 of the study, patients with primary refractory DLBCL (defined as progression of disease within 24 weeks after first line of treatment).
3) For Part 2 and Part 3 of the study, patients that are eligible to undergo first time HD-ASCT.
4) For Part 2 and Part 3 of the study, patients with R/R FL, MZL/MALT, MCL, or any other NHL subtypes according to the WHO classification.
5) The following exclusions, with regard to prior therapy apply:
- Not recovered from prior chemotherapy or radiation as per Investigator’s judgment.
- Anti-CD20 monoclonal antibody therapy within 14 days of starting study treatment.
- Prior therapy with other anti-CD37-targeting therapy.
- Radioimmunotherapy within two months prior to starting study treatment.
- Small molecule anti-cancer therapeutic agent, and all investigational agents within 5 x t½ or 14 days whichever is shorter.
- Allogeneic stem cell transplantation in the safety run-in period. In Part 2 and Part 3 of the study, patients who have had an allogeneic stem cell transplant may be eligible if their GVHD is controlled, after investigator/Sponsor discussion.
- Chronic, systemic treatment with corticosteroids unless the dose has been stable for >7 days and is equivalent to = 10 mg of prednisone per day.
- Patients who have not recovered from prior surgery. Patients must have recovered or stabilized from the side effects of any major or minor surgical procedures prior to study treatment.
6) Patients who have had a prior anaphylactic or other severe infusion reaction such that the patient is unable to tolerate antibody administration.
7) Patients who have known central nervous system, meningeal, or epidural disease including brain metastases.
8) Patients who have received or are to receive vaccination with live viruses within 30 days of Cycle 1 Day1.
9) Impaired cardiac function or clinically significant cardiac disease such as:
- New York Heart Association Class III or IV cardiac disease, including preexisting clinically significant ventricular arrhythmia, congestive heart failure, or cardiomyopathy;
- Unstable angina pectoris = 6 months prior to starting study drug;
- Acute myocardial infarction = 6 months prior to starting study drug; or
- Other clinically significant heart disease e.g., = grade 3 hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen.
10) Patients with = Grade 2 peripheral neuropathy.
11) Patients with active hepatitis A, B or C infection.
12) Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, psychiatric illness that would limit compliance with study requirements, active autoimmune disease requiring immunosuppressive therapy, severe immune deficiency.
13) Known diagnosis of human immunodeficiency virus (HIV) infection.
14) Patients with a concurrent primary malignancy that requires treatment or that would confound the disease response interpretation for the disease under study.
15) WCBP who are pregnant or breast feeding.
16) Patients currently presenting interstitial lung disease, diffuse parenchymal lung disease, or with a past history of severe/Grade 3 parenchymal lung disorders.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method