A study investigating the efficacy and safety of copanlisib versus placebo in patients with rituximab-refratory indolent non-Hodgkin's lymphoma.

Phase 1

• Conditions: Patients with rituximab-refractory indolent non-Hodgkin's lymphoma; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-000925-19-IE
• Lead Sponsor: Bayer AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-04-10
• Last Update Posted: 3 July 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 34

Inclusion Criteria

1. Ability to understand and willingness to sign written informed consent. Signed informed consent must be obtained before any study specific procedure.

2. Histologically confirmed diagnosis of indolent B-cell NHL, with histological subtype limited to the following:
o Follicular lymphoma (FL) grade 1-2-3a.
o Small lymphocytic lymphoma (SLL) with absolute lymphocyte count < 5 x 109/L at the time of diagnosis and at study entry.
o Lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM).
o Marginal zone lymphoma (MZL) (splenic, nodal, or extra-nodal).

3. Patients must have received two or more prior lines of treatment. A previous regimen is defined as one of the following: at least two months of single-agent therapy, at least two consecutive cycles of
polychemotherapy, autologous transplant, radioimmunotherapy.

4. Prior therapy must include rituximab and alkylating agent(s). Prior exposure to idelalisib or other PI3K inhibitors is acceptable (except to copanlisib)provided that there is no resistance.

5. Patients must be refractory to the last rituximab-based treatment defined as no response or response lasting < 6 months after completion of Treatment. Time interval to assess refractoriness will be calculated between the end date (last day) of the last rituximab-containing Regimen and the day of diagnosis confirmation of the subsequent relapse.

6. Patients must have at least one bi-dimensionally measurable lesion (which has not been previously irradiated) according to the Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification.

7. Patients affected by WM, who do not have at least one bi-dimensionally measurable lesion in the baseline radiologic assessment, must have measurable disease, defined as presence of immunoglobulin M (IgM) paraprotein with a minimum IgM level = 2 x
upper limit of normal (ULN) and positive immunofixation test.

8. Male or female patients = 18 years of age.

9. ECOG performance status = 1.

10. Life expectancy of at least 3 months.

11. Availability of fresh (preferred) and/or archival tumor tissue at Screening.

12. Women of childbearing potential (WOCBP) and men must agree to use effective contraception when sexually active. This applies for the time period between signing of the ICF and 3 months after the last administration of study treatment. A woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include but are not limited to hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for continuous 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy.
o The investigator or a designated associate is requested to advise the patient how to achieve highly effective birth control (failure rate of less than 1%), e.g. intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner and sexual abstinence.
o The use of condoms by male patients is required unless the female partner is permanently sterile.

13. Adequate bone marrow, liver and renal function as assessed by the following labor

Exclusion Criteria

1. Previous assignment to treatment.
2. Close affiliation with investigational site.
3. Histologically confirmed diagnosis of FL grade 3b.
4. Chronic lymphocytic leukemia.
5. Transformed disease: histological confirmation of transformation, or clinical and laboratory signs: rapid disease progression, high standardized uptake value (>12) by positron emission tomography at baseline if PET scans performed.
6. Previous/concurrent cancer that is distinct in primary site/histology from indolent B-cell NHL within 5 yrs before start of study treatment except for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors [Ta, Tis & T1].
8. Bulky disease -Lymph nodes/tumor mass (except spleen) =7cm LDi.
11. Known lymphomatous involvement of the central nervous system.
12. Congestive heart failure >NYHA class 2.
13. Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 mths). Myocardial infarction less than 6 mths before start of study treatment.
14. Uncontrolled arterial hypertension despite optimal medical Management (per investigators assessment).
15. Type I/II diabetes mellitus with HbA1c >8.5% at Screening.
16. Arterial or venous thrombotic or embolic events such as cerebrovascular accident, deep vein thrombosis or pulmonary embolism within 6 mths before start of study treatment.
17. Non-healing wound, ulcer, or bone fracture.
18. Active clinically serious infections >CTCAE Grade 2.
19. Known history of HIV infection.
20. Hepatitis B or C. All patients must be screened for HBV and HCV up to 28 days before start of study treatment using the routine hepatitis virus laboratory panel. Patients positive for HBsAg or HBcAb will be eligible if negative for HBV-DNA. Patients positive for HCV IgG will be eligible if negative for HCV-RNA.
21. Patients with seizure disorder requiring medication.
22. Patients with evidence or history of bleeding diathesis. Any hemorrhage or bleeding event =CTCAE Grade 3 within 4 wks before start of treatment.
23. Renal failure requiring hemo- or peritoneal dialysis.
24. Proteinuria =CTCAE Grade 3 as assessed by either 24h total urine protein quantification or a urine protein to creatinine ratio (UPCR) >3.5 on a random urine sample.
25. History/concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function.
26. Concurrent diagnosis of phaeochromocytoma.
27. Pregnant/breast-feeding patients. Women of childbearing potential must have a serum pregnancy test performed a max. of 7 days before start of study treatment, and a negative result must be documented before start of study treatment.
28. Unresolved toxicity >CTCAE Grade 1 attributed to any prior therapy/procedure excluding alopecia and =CTCAE Grade 2 peripheral neuropathy.
29. Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation.
30. Substance abuse, medical, psychological or social conditions that may interfere with the patient’s participation in the study or evaluation of the study results.
31. Any illness/medical conditions that are unstable or could jeopardize the safety of the patient and his/her compliance in study.
33. Treatment with investigational drugs within 28 days before start of study treatment.
34. Ongoing immunosuppressive therapy.
35. Radiotherapy or immuno/chemotherapy within 4 wks before start of study treatment.
36. Radioimmunotherapy/autologous transplant within 3 mths before start of

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified