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-PL
• Lead Sponsor: Bayer AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-01-13
• Last Update Posted: 20 August 2018

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 bidimensionally
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 postmenopausal
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
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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
par

Exclusion Criteria

1. Previous assignment to treat.
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 lab. 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 y. 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 m.). Myocardial infarction less than 6 m.
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 m. 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 w. 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 d. 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 d. before start of
study treatment.
34. Ongoing immunosuppressive therapy.
35. Radiotherapy or immuno/chemotherapy within 4 w. before start of
study treatment.
36. Radioimmunotherapy/autologous trans

Study & Design

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