Open-label, Uncontrolled Phase II Trial of Intravenous PI3K Inhibitor BAY80-6946 in Patients With Relapsed, Indolent or Aggressive Non-Hodgkin's Lymphomas
Sponsor
Bayer (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT01660451
Collaborator
(none)
227
101
3
123.6
2.2
0
Study Details
Study Description
Brief Summary
The objective of the study (part A) is to evaluate the efficacy and safety of BAY80-6946 in patients with indolent or aggressive Non-Hodgkin's Lymphoma, who have progressed after standard therapy. 30 patients will be enrolled to both indolent and aggressive disease group. The objective of the study part B (CHRONOS-1) is to evaluate the efficacy and safety of BAY80-6946 in patients with relapsed/refractory follicular lymphoma. 120 patients will be enrolled in the part B of the study. Further objectives are to evaluate the pharmacokinetics and biomarkers. Quality of life will be a further objective of part B of the study.
In a cohort of 20 patients (enrolled both in part A and B) an ECG substudy will be performed to assess the potential for cardiac toxicity and QT/QTc interval prolongation of BAY80-6946.
After an up to 28-day screening period, eligible patients will start treatment with BAY80-6946 at a dose of 0.8 mg/kg (Part A) and at a dose of 60 mg (Part B).
Treatment will be continued until disease has progressed or until another criterion is met for withdrawal from study. An end-of-treatment visit will be performed within 7 days after discontinuation of study treatment. Thirty to 35 days after last study drug administration, a safety followup visit will be performed for the collection of adverse events (AEs) and concomitant medication data. Patients will be contacted quarterly to determine overall survival status up to 4 years after last patient first treatment. Patients who discontinue study drug for reasons other than disease progression will enter the Active Assessment Follow-up period. Once the study is analyzed for survival at 4 years after last patient started study treatment, any patient still on treatment may continue to be treated and followed under a separate provision to be determined (e.g. roll-over-study). The end of study notification to Health Authorities will be based on the completion of the collection of survival data.
The efficacy is measured by the decrease in tumor size. Tumor assessments will be done at Screening, every 8 weeks during Year 1, every 12 weeks during Year 2, and every 6 months during Year 3. Blood samples will be collected for pharmacokinetic analysis. Archival tumor tissue and blood samples will be collected for biomarker analysis (mandatory) and for central pathology review (part B), fresh biopsy tissue will also be collected if available.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
227 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Open-label, Uncontrolled Phase II Trial of Intravenous PI3K Inhibitor BAY80-6946 in Patients With Relapsed, Indolent or Aggressive Non-Hodgkin's Lymphomas
Actual Study Start Date
:
Nov 19, 2012
Actual Primary Completion Date
:
Jun 22, 2016
Anticipated Study Completion Date
:
Mar 8, 2023
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Copanlisib (indolent NHL) Part A: Participants in this arm will be patients with indolent NHL. |
Drug: Copanlisib (Aliqopa, BAY80-6946)
BAY 80-6946 is administered in a normal saline solution, 100 mL, intravenously over 1h. No intravenous glucose preparations should be administered on the days of infusion. Dosing is weekly for the first 3 weeks (on Days 1, 8, and 15) of a 28-day cycle, followed by a 1-week break (i.e., no infusion on Day 22).
Part A: The individual dose will be 0.8 mg/kg (max. 65 mg) per infusion from Cycle 1 on. The maximum dose of 65 mg should never be exceeded.
Part B: The individual dose will be 60 mg per infusion from Cycle 1 on.
|
| Experimental: Copanlisib (aggressive NHL) Part A: Participants in this arm will be patients with aggressive NHL. |
Drug: Copanlisib (Aliqopa, BAY80-6946)
BAY 80-6946 is administered in a normal saline solution, 100 mL, intravenously over 1h. No intravenous glucose preparations should be administered on the days of infusion. Dosing is weekly for the first 3 weeks (on Days 1, 8, and 15) of a 28-day cycle, followed by a 1-week break (i.e., no infusion on Day 22).
Part A: The individual dose will be 0.8 mg/kg (max. 65 mg) per infusion from Cycle 1 on. The maximum dose of 65 mg should never be exceeded.
Part B: The individual dose will be 60 mg per infusion from Cycle 1 on.
|
| Experimental: Copanlisib (indolent B-cell NHL) Part B: Participants in this arm will be patients with indolent B-cell NHL. |
Drug: Copanlisib (Aliqopa, BAY80-6946)
BAY 80-6946 is administered in a normal saline solution, 100 mL, intravenously over 1h. No intravenous glucose preparations should be administered on the days of infusion. Dosing is weekly for the first 3 weeks (on Days 1, 8, and 15) of a 28-day cycle, followed by a 1-week break (i.e., no infusion on Day 22).
Part A: The individual dose will be 0.8 mg/kg (max. 65 mg) per infusion from Cycle 1 on. The maximum dose of 65 mg should never be exceeded.
Part B: The individual dose will be 60 mg per infusion from Cycle 1 on.
|
Outcome Measures
Primary Outcome Measures
- Objective Response Rate (ORR) Based on Independent Review-Part A [Baseline up to the last patient has completed the 16 weeks of treatment]
Objective response rate was defined as the proportion of participants with a best response rating of complete response (CR), unconfirmed complete response (CRu) or partial response (PR), based on the Report of an International Workshop to Standardize Response Criteria for non-Hodgkins Lymphomas, Cheson, 1999, as evaluated by the Independent Response Adjudication Committee (IRAC). For chronic lymphocytic leukemia (CLL) patients Hallek criteria (2008) were used and assessed by investigator.
- Objective Response Rate (ORR) Based on Independent Review-Part B [Baseline up to the last patient has completed the 16 weeks of treatment]
Objective response rate was defined as the proportion of participants with a best response rating of CR or PR, based on the International Working Group Revised response Criteria for Malignant Lymphoma, Cheson 2007.
- ORR Based on Investigator Assessment-Part A [Baseline up to the last patient has completed the 16 weeks of treatment]
Objective response rate was defined as the proportion of participants with a best response rating of CR, CRu or PR, based on the Report of an International Workshop to Standardize Response Criteria for non-Hodgkins Lymphomas, Cheson, 1999. For CLL patients Hallek criteria (2008) were used and assessed by investigator.
- ORR Based on Investigator Assessment-Part B [Baseline up to the last patient has completed the 16 weeks of treatment]
Objective response rate was defined as the proportion of participants with a best response rating of CR or PR, based on the International Working Group Revised response Criteria for Malignant Lymphoma, Cheson 2007.
Secondary Outcome Measures
- Duration of Response (DOR) Based on Independent Review [Baseline up to the last patient has completed the 16 weeks of treatment]
Duration of response (DOR) was defined as the time (in days) from the date of the first observed tumor response of CR or PR (whichever was noted earlier) to first subsequent disease progression (either first progressive disease [PD], first clinical progression or first adverse event [AE] associated with clinical disease progression) or death caused by disease progression, if this death occurred before progression was documented. All deaths were considered as 'caused by disease progression' except deaths with the reason "other" or "AE not related to disease progression.
- DOR Based on Investigator Assessment [Baseline up to the last patient has completed the 16 weeks of treatment]
Duration of response (DOR) was defined as the time (in days) from the date of the first observed tumor response of CR or PR (whichever was noted earlier) to first subsequent disease progression (either first progressive disease [PD], first clinical progression or first adverse event [AE] associated with clinical disease progression) or death caused by disease progression, if this death occurred before progression was documented. All deaths were considered as 'caused by disease progression' except deaths with the reason "other" or "AE not related to disease progression.
- Progression Free Survival (PFS) Based on Independent Review [Baseline up to the last patient has completed the 16 weeks of treatment]
PFS was defined as the time (in days) from the date of the first treatment to the date of first observed PD (radiological or clinical, or first AE associated with clinical PD, whichever was earlier) or death due to any cause (if death occurred before progression was documented).
- PFS Based on Investigator Assessment [Baseline up to the last patient has completed the 16 weeks of treatment]
PFS was defined as the time (in days) from the date of the first treatment to the date of first observed PD (radiological or clinical, or first AE associated with clinical PD, whichever was earlier) or death due to any cause (if death occurred before progression was documented).
- Overall Survival (OS) [Baseline up to the last patient has completed the 16 weeks of treatment]
OS was defined as the time (in days) from the date of first administration of study treatment to death due to any cause.
- Functional Assessment of Cancer Therapy - Lymphoma Lymphoma Subscale (FACT-Lym LymS) at Week 16 - Part B [Baseline up to the last patient has completed the 16 weeks of treatment]
HRQoL assessment was used to describe development of patients with copanlisib by using FACT-Lym questionnaire assessment tool. It contains 42 items (questions) covering HRQoL, common lymphoma symptoms and treatment side-effects. The FACT - General (FACT-G) questionnaire contains 27 items covering 4 core HRQoL subscales: Physical Wellbeing (7 items), Social/Family Wellbeing (7), Emotional Wellbeing (6), and Functional Wellbeing (7). The FACT-Lym also includes an Additional Concerns subscale (15 items) (FACT-Lym LymS), addressing issues typically experienced by lymphoma patients. Some of the issues covered include pain, itching, night sweats, trouble sleeping, fatigue and trouble concentrating. FACT-Lym also asks patients about lumps and swelling, fevers, infections, weight, appetite, emotional stability and treatment. Score range for the FACT-Lym LymS was 0 - 60, higher score represent less symptoms. Here in below table "n" signifies evaluable participants for the respective category.
- Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Total Score at Week 16 - Part B [Baseline up to the last patient has completed the 16 weeks of treatment]
HRQoL assessment was used to describe development of patients with copanlisib by using FACT-Lym questionnaire assessment tool. It contains 42 items (questions) covering HRQoL, common lymphoma symptoms and treatment side-effects. The FACT - General (FACT-G) questionnaire contains 27 items covering 4 core HRQoL subscales: Physical Wellbeing (7 items), Social/Family Wellbeing (7), Emotional Wellbeing (6), and Functional Wellbeing (7). The FACT-Lym also includes an Additional Concerns subscale (15 items) (FACT-Lym LymS), addressing issues typically experienced by lymphoma patients. Some of the issues covered include pain, itching, night sweats, trouble sleeping, fatigue and trouble concentrating. FACT-Lym also asks patients about lumps and swelling, fevers, infections, weight, appetite, emotional stability and treatment. FACT-Lym total score range was 0-168, higher score indicates better HRQoL. Here, in the below table "n" signifies evaluable participants for the respective category.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Indolent NHL:
-
Histologically confirmed diagnosis of follicular lymphoma (FL) grades 1, 2 or 3a, marginal zone lymphoma (including nodal or splenic marginal zone B-cell lymphoma and mucosa-associated lymphoid tissue [MALT] lymphoma), lymphoplasmacytic lymphoma/Waldenström macroglobulinemia, chronic lymphocytic leukemia (CLL).
-
Relapsed after ≥ 2 prior chemotherapy- or immunotherapy-based regimens for indolent NHL, or refractory to 2 prior chemotherapy and/ or immunotherapy-based regimens.
-
Aggressive NHL:
-
Histologically confirmed diagnosis of grade 3b follicular lymphoma (FL), transformed indolent lymphoma, diffuse large B-cell lymphoma (DLBCL), mediastinal large B-cell lymphoma, mantle cell lymphoma (MCL), peripheral T-cell lymphoma unspecified, or anaplastic large cell lymphoma primary systemic type, or angioimmunoblastic T cell lymphoma.
-
Relapsed after ≥ 2 prior chemotherapy regimens, including the following: First-line treatment with standard anthracycline-containing regimen (e.g., cyclophosphamide, doxorubicin, vincristine, and prednisone or equivalent). At least 1 additional combination chemotherapy regimen. Patients relapsed after or refractory to first prior chemotherapy- and/or immunotherapy-based regimen for aggressive NHL and not eligible for high-dose regimen followed by transplant. High-dose chemotherapy, or chemoradiotherapy with autologous stem cell transplantation is considered 1 regimen. Patients with CD20 expressing neoplastic cells must have received prior rituximab, if available.
-
Patients with transformed indolent lymphoma must have received at least 2 prior chemotherapy- and/or immunotherapy-based regimens
-
Consent to provide fresh tumor tissue during screening
-
Indolent B-cell NHL lymphoma (study part B):
-
Histologically confirmed diagnosis of indolent B-cell NHL, with histological subtype limited to the following:
-
Follicular lymphoma (FL) grade 1-2-3a
-
Small lymphocytic lymphoma (SLL) with absolute lymphocyte count < 5 x 109/L at the time of diagnosis and at study entry
-
Lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM)
-
Marginal zone lymphoma (MZL) (splenic, nodal, or extranodal)
-
Relapsed or refractory after ≥ 2 prior lines of therapy (refractory defined as not responding to a standard regimen or progressing within 6 months of the last course of a standard regimen). Patients must have received Rituximab and alkylating agents.
-
For all patients:
-
Male or female patients > 18 years of age
-
ECOG performance status ≤ 2 (ECOG: Eastern Cooperative Oncology Group)
-
Life expectancy of at least 3 months
-
Adequate bone marrow, liver and renal function as assessed within 7 days before starting study treatment
-
Left ventricular ejection fraction (LVEF) ≥ lower limit of normal (LLN) for the Institution
-
Availability of archival tumor tissue
Exclusion Criteria:
-
Uncontrolled hypertension (blood pressure ≥ 150/90 mmHg despite optimal medical management)
-
Patients with evidence or history of bleeding diathesis. Any hemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks of start of study medication (CTCAE: Common Terminology Criteria for Adverse Events).
-
History or concurrent condition of interstitial lung disease
-
Unresolved toxicity higher than CTCAE grade 1 (NCI-CTC version 4.0) attributed to any prior therapy/procedure excluding alopecia. (NCI: National Cancer Institute)
-
Prior treatment with PI3K inhibitors
-
Systemic corticosteroid therapy (ongoing)
-
Hepatitis B or C. All subjects must be screened for hepatitis B and C up to 28 days prior to study drug start using the hepatitis virus panel laboratorial routine. Subjects positive for HBsAg or HBcAb will be eligible if they are negative for HBV-DNA; subjects positive for HCV IgG will be eligible if they are negative for HCV RNA.
-
For Part B:
-
Histologically confirmed diagnosis of follicular lymphoma grade 3b or transformed disease and chronic lymphocytic leukemia (CLL)
-
History or concurrent condition of interstitial lung disease or severely impaired pulmonary function
-
Excluded medical conditions:
-
Previous or concurrent cancer that is distinct in primary site or histology from indolent B-cell NHL within 5 years prior to treatment start EXCEPT for curatively treated cervical cancer in situ, nonmelanoma skin cancer and superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)].
-
Hepatitis B or C. All subjects must be screened for hepatitis B and C up to 28 days prior to study drug start using the hepatitis virus panel laboratorial routine. Subjects positive for HBsAg or HBcAb will be eligible if they are negative for HBV-DNA; subjects positive for HCV IgG will be eligible if they are negative for HCV-RNA.
-
Type I or II diabetes mellitus with HbA1c > 8.5% or fasting plasma glucose > 160 mg/dL at screening.
-
Previous or concurrent cancer that is distinct in primary site or histology from indolent B-cell NHL within 5 years prior to treatment start EXCEPT for curatively treated cervical cancer in situ, nonmelanoma skin cancer and superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)].
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Birmingham | Alabama | United States | 35213 | |
| 2 | Gilbert | Arizona | United States | 85234 | |
| 3 | Anaheim | California | United States | 90801 | |
| 4 | Aurora | Colorado | United States | 80012 | |
| 5 | Englewood | Colorado | United States | 80113 | |
| 6 | Fort Collins | Colorado | United States | 80528 | |
| 7 | Port Saint Lucie | Florida | United States | 34952 | |
| 8 | Louisville | Kentucky | United States | 40207 | |
| 9 | Detroit | Michigan | United States | 48202 | |
| 10 | Saint Louis Park | Minnesota | United States | 55426 | |
| 11 | Lake Success | New York | United States | 11042 | |
| 12 | Goldsboro | North Carolina | United States | 27534 | |
| 13 | Canton | Ohio | United States | 44718 | |
| 14 | San Antonio | Texas | United States | 78229 | |
| 15 | Spokane | Washington | United States | 99208-1129 | |
| 16 | Garran | Australian Capital Territory | Australia | 2605 | |
| 17 | Linz | Austria | 4020 | ||
| 18 | Anderlecht | Belgium | 1070 | ||
| 19 | Bruxelles - Brussel | Belgium | 1200 | ||
| 20 | Gent | Belgium | 9000 | ||
| 21 | Leuven | Belgium | 3000 | ||
| 22 | Turnhout | Belgium | 2300 | ||
| 23 | Wilrijk | Belgium | 2610 | ||
| 24 | Sofia | Bulgaria | 1431 | ||
| 25 | Saint John | New Brunswick | Canada | E2L 4L2 | |
| 26 | Montreal | Quebec | Canada | H1T 2M4 | |
| 27 | Montreal | Quebec | Canada | H3T 1E2 | |
| 28 | Helsinki | Finland | 00290 | ||
| 29 | Oulu | Finland | 90020 | ||
| 30 | Tampere | Finland | 33521 | ||
| 31 | Turku | Finland | FIN-20521 | ||
| 32 | Brest | France | 29285 | ||
| 33 | Creteil | France | 94010 | ||
| 34 | La Roche Sur Yon | France | 85925 | ||
| 35 | Lille | France | 59037 | ||
| 36 | PARIS cedex | France | 75475 | ||
| 37 | Pessac | France | 33600 | ||
| 38 | Pierre Benite | France | 69495 | ||
| 39 | Poitiers | France | 86021 | ||
| 40 | Rouen | France | 76038 | ||
| 41 | Vandoeuvre-les-nancy | France | 54500 | ||
| 42 | München | Bayern | Germany | 81377 | |
| 43 | Potsdam | Berlin | Germany | 14467 | |
| 44 | Münster | Nordrhein-Westfalen | Germany | 48149 | |
| 45 | Recklinghausen | Nordrhein-Westfalen | Germany | 45659 | |
| 46 | Mainz | Rheinland-Pfalz | Germany | 55131 | |
| 47 | Dresden | Sachsen | Germany | 01307 | |
| 48 | Berlin | Germany | 10967 | ||
| 49 | Berlin | Germany | 13353 | ||
| 50 | Athens | Greece | 11526 | ||
| 51 | Hong Kong | Hong Kong | |||
| 52 | Shatin | Hong Kong | |||
| 53 | Budapest | Hungary | 1083 | ||
| 54 | Budapest | Hungary | 1097 | ||
| 55 | Kaposvar | Hungary | 7400 | ||
| 56 | Galway | Ireland | H91 YR71 | ||
| 57 | Petach Tikva | Israel | 4941492 | ||
| 58 | Ramat Gan | Israel | 5262000 | ||
| 59 | Zerifin | Israel | 7030000 | ||
| 60 | Napoli | Campania | Italy | 80131 | |
| 61 | Bologna | Emilia-Romagna | Italy | 40138 | |
| 62 | Roma | Lazio | Italy | 00161 | |
| 63 | Brescia | Lombardia | Italy | 25123 | |
| 64 | Milano | Lombardia | Italy | 20089 | |
| 65 | Torino | Piemonte | Italy | 10126 | |
| 66 | Busan | Busan Gwang''yeogsi | Korea, Republic of | 49201 | |
| 67 | Seoul | Seoul Teugbyeolsi | Korea, Republic of | 03080 | |
| 68 | Seoul | Korea, Republic of | 06351 | ||
| 69 | Christchurch | New Zealand | |||
| 70 | Gdynia | Poland | 81-519 | ||
| 71 | Krakow | Poland | 30-510 | ||
| 72 | Lisboa | Portugal | 1099-023 | ||
| 73 | Kemerovo | Russian Federation | 650066 | ||
| 74 | Moscow | Russian Federation | 129128 | ||
| 75 | Nizhny Novgorod | Russian Federation | 603126 | ||
| 76 | Omsk | Russian Federation | 644013 | ||
| 77 | Saratov | Russian Federation | 410053 | ||
| 78 | St. Petersburg | Russian Federation | 197101 | ||
| 79 | Singapore | Singapore | 169608 | ||
| 80 | Singapore | Singapore | 169610 | ||
| 81 | Majadahonda | Madrid | Spain | 28222 | |
| 82 | Marbella | Málaga | Spain | 29603 | |
| 83 | Barcelona | Spain | 08036 | ||
| 84 | Madrid | Spain | 28050 | ||
| 85 | Sevilla | Spain | 41009 | ||
| 86 | Valencia | Spain | 46026 | ||
| 87 | Uddevalla | Sweden | 451 80 | ||
| 88 | Ankara | Turkey | 06100 | ||
| 89 | Istanbul | Turkey | 34093 | ||
| 90 | Izmir | Turkey | 35100 | ||
| 91 | Izmir | Turkey | 35340 | ||
| 92 | Cambridge | Cambridgeshire | United Kingdom | CB2 0QQ | |
| 93 | Plymouth | Devon | United Kingdom | PL6 8DH | |
| 94 | Southampton | Hampshire | United Kingdom | SO16 6YD | |
| 95 | Harrow | London | United Kingdom | HA1 3UJ | |
| 96 | Liverpool | Merseyside | United Kingdom | L7 8XP | |
| 97 | Sutton | Surrey | United Kingdom | SM2 5PT | |
| 98 | Birmingham | West Midlands | United Kingdom | B9 5SS | |
| 99 | Leeds | United Kingdom | LS9 7TF | ||
| 100 | Manchester | United Kingdom | M20 4BX | ||
| 101 | Romford | United Kingdom | RM7 0AG |
Sponsors and Collaborators
- Bayer
Investigators
- Study Director: Bayer Study Director, Bayer
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Bayer
ClinicalTrials.gov Identifier:
NCT01660451
Other Study ID Numbers:
- 16349
- 2012-002602-52
First Posted:
Aug 8, 2012
Last Update Posted:
Feb 24, 2022
Last Verified:
Jan 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Bayer
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Part A-Study enrolled participants from 41 study centers in 10 countries, between 19 NOV 2012 (first participant first visit [FPFV]) and 01 OCT 2015 (cut-off date for interim analysis). Part B-Study enrolled participants from 81 study centers in 24 countries, between 04 NOV 2013 (FPFV) and 22 JUN 2016 (cut-off date for primary analysis). |
|---|---|
| Pre-assignment Detail | Part A: Overall 125 participants were screened, of them 41 were screen failure. Total 84 were assigned to treatment. Part B: Overall 213 participants were screened, of them 70 were screen failure. Total 143 were assigned to treatment, of them 1 was suspected as fraudulent and excluded from analysis sets. Therefore 142 participants were evaluable. |
| Arm/Group Title | Part A: Indolent NHL/CLL | Part A: Aggressive NHL | Part B: Indolent NHL |
|---|---|---|---|
| Arm/Group Description | Participants with indolent Non-Hodgkin's lymphoma/Chronic lymphocytic leukemia [iNHL/CLL] received copanlisib 0.8 milligram per kilogram (mg/kg), maximum 65 mg, intravenous (IV) infusion dosing over 1 hour in 100 milliliter (mL) normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study. | Participants with aggressive NHL (aNHL) received copanlisib 0.8 mg/kg, maximum 65 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study. | Participants with indolent B-cell NHL received copanlisib 60 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Revised Response Criteria for Malignant Lymphoma by Cheson et al., 2007, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study. |
| Period Title: Overall Study | |||
| STARTED | 33 | 51 | 142 |
| COMPLETED | 16 | 34 | 37 |
| NOT COMPLETED | 17 | 17 | 105 |
Baseline Characteristics
| Arm/Group Title | Part A: Indolent NHL/CLL | Part A: Aggressive NHL | Part B: Indolent NHL | Total |
|---|---|---|---|---|
| Arm/Group Description | Participants with indolent Non-Hodgkin's lymphoma/Chronic lymphocytic leukemia [iNHL/CLL] received copanlisib 0.8 milligram per kilogram (mg/kg), maximum 65 mg, intravenous (IV) infusion dosing over 1 hour in 100 milliliter (mL) normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study. | Participants with aggressive NHL (aNHL) received copanlisib 0.8 mg/kg, maximum 65 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study. | Participants with indolent B-cell NHL received copanlisib 60 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Revised Response Criteria for Malignant Lymphoma by Cheson et al., 2007, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study. | Total of all reporting groups |
| Overall Participants | 33 | 51 | 142 | 226 |
| Age, Customized (Number) [Number] | ||||
| 18 to 90 years |
33
100%
|
51
100%
|
142
100%
|
226
100%
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
18
54.5%
|
22
43.1%
|
71
50%
|
111
49.1%
|
| Male |
15
45.5%
|
29
56.9%
|
71
50%
|
115
50.9%
|
Outcome Measures
| Title | Objective Response Rate (ORR) Based on Independent Review-Part A |
|---|---|
| Description | Objective response rate was defined as the proportion of participants with a best response rating of complete response (CR), unconfirmed complete response (CRu) or partial response (PR), based on the Report of an International Workshop to Standardize Response Criteria for non-Hodgkins Lymphomas, Cheson, 1999, as evaluated by the Independent Response Adjudication Committee (IRAC). For chronic lymphocytic leukemia (CLL) patients Hallek criteria (2008) were used and assessed by investigator. |
| Time Frame | Baseline up to the last patient has completed the 16 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per protocol set included all patients treated with study drug and evaluated for ORR and had no major protocol deviation. (In Part A, for CLL patients, there was no independent assessment. Instead, the investigator assessment had been used.) |
| Arm/Group Title | Part A: Indolent NHL/CLL | Part A: Aggressive NHL |
|---|---|---|
| Arm/Group Description | Participants with indolent Non-Hodgkin's lymphoma/Chronic lymphocytic leukemia [iNHL/CLL] received copanlisib 0.8 milligram per kilogram (mg/kg), maximum 65 mg, intravenous (IV) infusion dosing over 1 hour in 100 milliliter (mL) normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study. | Participants with aggressive NHL (aNHL) received copanlisib 0.8 mg/kg, maximum 65 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study. |
| Measure Participants | 32 | 48 |
| Number (90% Confidence Interval) [percentage of participants] |
43.75
132.6%
|
27.08
53.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part A: Indolent NHL/CLL |
|---|---|---|
| Comments | Response rate was statistically compared by exact binomial test if higher than 5%. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0001 |
| Comments | 0.0001 | |
| Method | Exact binomial test | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Response rate |
| Estimated Value | 45.45 | |
| Confidence Interval |
(2-Sided) 90% 30.49 to 61.06 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Part A: Aggressive NHL |
|---|---|---|
| Comments | Response rate was statistically compared by exact binomial test if higher than 5%. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0001 |
| Comments | 0.0001 | |
| Method | Exact binominal test | |
| Comments | P-value was based on the original patients in the aggressive arm (for the first 34 patients), not including the additional recruited patients. | |
| Method of Estimation | Estimation Parameter | Response rate |
| Estimated Value | 27.08 | |
| Confidence Interval |
(2-Sided) 90% 16.83 to 39.57 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Objective Response Rate (ORR) Based on Independent Review-Part B |
|---|---|
| Description | Objective response rate was defined as the proportion of participants with a best response rating of CR or PR, based on the International Working Group Revised response Criteria for Malignant Lymphoma, Cheson 2007. |
| Time Frame | Baseline up to the last patient has completed the 16 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all patients assigned to study treatment. |
| Arm/Group Title | Part B: Indolent NHL |
|---|---|
| Arm/Group Description | Participants with indolent B-cell NHL received copanlisib 60 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Revised Response Criteria for Malignant Lymphoma by Cheson et al., 2007, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study. |
| Measure Participants | 142 |
| Number (95% Confidence Interval) [percentage of participants] |
59.15
179.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part A: Indolent NHL/CLL |
|---|---|---|
| Comments | Response rate was statistically compared by exact binomial test if higher than 40%. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | 0.001 | |
| Method | Exact binominal test | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Response rate |
| Estimated Value | 59.15 | |
| Confidence Interval |
(2-Sided) 95% 50.60 to 67.32 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | ORR Based on Investigator Assessment-Part A |
|---|---|
| Description | Objective response rate was defined as the proportion of participants with a best response rating of CR, CRu or PR, based on the Report of an International Workshop to Standardize Response Criteria for non-Hodgkins Lymphomas, Cheson, 1999. For CLL patients Hallek criteria (2008) were used and assessed by investigator. |
| Time Frame | Baseline up to the last patient has completed the 16 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per protocol set included all patients treated with study drug and evaluated for ORR and had no major protocol deviation. Patients who were not evaluable for ORR and discontinued due to a drug-related toxicity, death / progression by clinical judgment before disease was re-evaluated and included. |
| Arm/Group Title | Part A: Indolent NHL/CLL | Part A: Aggressive NHL |
|---|---|---|
| Arm/Group Description | Participants with indolent Non-Hodgkin's lymphoma/Chronic lymphocytic leukemia [iNHL/CLL] received copanlisib 0.8 milligram per kilogram (mg/kg), maximum 65 mg, intravenous (IV) infusion dosing over 1 hour in 100 milliliter (mL) normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study. | Participants with aggressive NHL (aNHL) received copanlisib 0.8 mg/kg, maximum 65 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study. |
| Measure Participants | 32 | 48 |
| Number (90% Confidence Interval) [percentage of participants] |
46.88
142.1%
|
31.25
61.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part A: Indolent NHL/CLL |
|---|---|---|
| Comments | Response rate was statistically compared by exact binomial test if higher than 5%. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0001 |
| Comments | 0.0001 | |
| Method | Exact binominal test | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Response rate |
| Estimated Value | 46.88 | |
| Confidence Interval |
(2-Sided) 90% 31.54 to 62.66 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Part A: Aggressive NHL |
|---|---|---|
| Comments | Response rate was statistically compared by exact binomial test if higher than 5%. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0001 |
| Comments | 0.0001 | |
| Method | Exact binominal test | |
| Comments | P-value was based on the original patients in the aggressive arm (for the first 34 patients), not including the additional recruited patients. | |
| Method of Estimation | Estimation Parameter | Response rate |
| Estimated Value | 31.25 | |
| Confidence Interval |
(2-Sided) 90% 20.35 to 43.97 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | ORR Based on Investigator Assessment-Part B |
|---|---|
| Description | Objective response rate was defined as the proportion of participants with a best response rating of CR or PR, based on the International Working Group Revised response Criteria for Malignant Lymphoma, Cheson 2007. |
| Time Frame | Baseline up to the last patient has completed the 16 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all patients assigned to study treatment. |
| Arm/Group Title | Part B: Indolent NHL |
|---|---|
| Arm/Group Description | Participants with indolent B-cell NHL received copanlisib 60 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Revised Response Criteria for Malignant Lymphoma by Cheson et al., 2007, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study. |
| Measure Participants | 142 |
| Number (95% Confidence Interval) [percentage of participants] |
51.41
155.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part A: Indolent NHL/CLL |
|---|---|---|
| Comments | Response rate was statistically compared by exact binomial test if higher than 40%. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0039 |
| Comments | 0.01 | |
| Method | Exact binominal test | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Response rate |
| Estimated Value | 51.41 | |
| Confidence Interval |
(2-Sided) 95% 42.88 to 59.87 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Duration of Response (DOR) Based on Independent Review |
|---|---|
| Description | Duration of response (DOR) was defined as the time (in days) from the date of the first observed tumor response of CR or PR (whichever was noted earlier) to first subsequent disease progression (either first progressive disease [PD], first clinical progression or first adverse event [AE] associated with clinical disease progression) or death caused by disease progression, if this death occurred before progression was documented. All deaths were considered as 'caused by disease progression' except deaths with the reason "other" or "AE not related to disease progression. |
| Time Frame | Baseline up to the last patient has completed the 16 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| PPS (for Part A) included all patients with study drug administration that were evaluable for objective tumor response and had no major protocol deviation. FAS (for Part B) included all patients assigned to study treatment. DOR was only evaluated for patients with at least one tumor response of CR, Cru (only for Part A) or PR. |
| Arm/Group Title | Part A: Indolent NHL/CLL | Part A: Aggressive NHL | Part B: Indolent NHL |
|---|---|---|---|
| Arm/Group Description | Participants with indolent Non-Hodgkin's lymphoma/Chronic lymphocytic leukemia [iNHL/CLL] received copanlisib 0.8 milligram per kilogram (mg/kg), maximum 65 mg, intravenous (IV) infusion dosing over 1 hour in 100 milliliter (mL) normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study. | Participants with aggressive NHL (aNHL) received copanlisib 0.8 mg/kg, maximum 65 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study. | Participants with indolent B-cell NHL received copanlisib 60 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Revised Response Criteria for Malignant Lymphoma by Cheson et al., 2007, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study. |
| Measure Participants | 14 | 13 | 84 |
| Median (95% Confidence Interval) [days] |
390
|
166
|
687
|
| Title | DOR Based on Investigator Assessment |
|---|---|
| Description | Duration of response (DOR) was defined as the time (in days) from the date of the first observed tumor response of CR or PR (whichever was noted earlier) to first subsequent disease progression (either first progressive disease [PD], first clinical progression or first adverse event [AE] associated with clinical disease progression) or death caused by disease progression, if this death occurred before progression was documented. All deaths were considered as 'caused by disease progression' except deaths with the reason "other" or "AE not related to disease progression. |
| Time Frame | Baseline up to the last patient has completed the 16 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| PPS (for Part A) included all patients with study drug administration that were evaluable for objective tumor response and had no major protocol deviation. FAS (for Part B) included all patients assigned to study treatment. DOR was only evaluated for patients with at least one tumor response of CR, Cru (only for Part A) or PR. |
| Arm/Group Title | Part A: Indolent NHL/CLL | Part A: Aggressive NHL | Part B: Indolent NHL |
|---|---|---|---|
| Arm/Group Description | Participants with indolent Non-Hodgkin's lymphoma/Chronic lymphocytic leukemia [iNHL/CLL] received copanlisib 0.8 milligram per kilogram (mg/kg), maximum 65 mg, intravenous (IV) infusion dosing over 1 hour in 100 milliliter (mL) normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study. | Participants with aggressive NHL (aNHL) received copanlisib 0.8 mg/kg, maximum 65 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study. | Participants with indolent B-cell NHL received copanlisib 60 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Revised Response Criteria for Malignant Lymphoma by Cheson et al., 2007, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study. |
| Measure Participants | 15 | 15 | 73 |
| Median (95% Confidence Interval) [days] |
287
|
166
|
370
|
| Title | Progression Free Survival (PFS) Based on Independent Review |
|---|---|
| Description | PFS was defined as the time (in days) from the date of the first treatment to the date of first observed PD (radiological or clinical, or first AE associated with clinical PD, whichever was earlier) or death due to any cause (if death occurred before progression was documented). |
| Time Frame | Baseline up to the last patient has completed the 16 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all patients assigned to study treatment. |
| Arm/Group Title | Part A: Indolent NHL/CLL | Part A: Aggressive NHL | Part B: Indolent NHL |
|---|---|---|---|
| Arm/Group Description | Participants with indolent Non-Hodgkin's lymphoma/Chronic lymphocytic leukemia [iNHL/CLL] received copanlisib 0.8 milligram per kilogram (mg/kg), maximum 65 mg, intravenous (IV) infusion dosing over 1 hour in 100 milliliter (mL) normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study. | Participants with aggressive NHL (aNHL) received copanlisib 0.8 mg/kg, maximum 65 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study. | Participants with indolent B-cell NHL received copanlisib 60 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Revised Response Criteria for Malignant Lymphoma by Cheson et al., 2007, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study. |
| Measure Participants | 33 | 51 | 142 |
| Median (95% Confidence Interval) [days] |
294
|
70
|
340
|
| Title | PFS Based on Investigator Assessment |
|---|---|
| Description | PFS was defined as the time (in days) from the date of the first treatment to the date of first observed PD (radiological or clinical, or first AE associated with clinical PD, whichever was earlier) or death due to any cause (if death occurred before progression was documented). |
| Time Frame | Baseline up to the last patient has completed the 16 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all patients assigned to study treatment. |
| Arm/Group Title | Part A: Indolent NHL/CLL | Part A: Aggressive NHL | Part B: Indolent NHL |
|---|---|---|---|
| Arm/Group Description | Participants with indolent Non-Hodgkin's lymphoma/Chronic lymphocytic leukemia [iNHL/CLL] received copanlisib 0.8 milligram per kilogram (mg/kg), maximum 65 mg, intravenous (IV) infusion dosing over 1 hour in 100 milliliter (mL) normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study. | Participants with aggressive NHL (aNHL) received copanlisib 0.8 mg/kg, maximum 65 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study. | Participants with indolent B-cell NHL received copanlisib 60 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Revised Response Criteria for Malignant Lymphoma by Cheson et al., 2007, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study. |
| Measure Participants | 33 | 51 | 142 |
| Median (95% Confidence Interval) [days] |
280
|
70
|
330
|
| Title | Overall Survival (OS) |
|---|---|
| Description | OS was defined as the time (in days) from the date of first administration of study treatment to death due to any cause. |
| Time Frame | Baseline up to the last patient has completed the 16 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all patients assigned to study treatment. |
| Arm/Group Title | Part A: Indolent NHL/CLL | Part A: Aggressive NHL | Part B: Indolent NHL |
|---|---|---|---|
| Arm/Group Description | Participants with indolent Non-Hodgkin's lymphoma/Chronic lymphocytic leukemia [iNHL/CLL] received copanlisib 0.8 milligram per kilogram (mg/kg), maximum 65 mg, intravenous (IV) infusion dosing over 1 hour in 100 milliliter (mL) normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study. | Participants with aggressive NHL (aNHL) received copanlisib 0.8 mg/kg, maximum 65 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study. | Participants with indolent B-cell NHL received copanlisib 60 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Revised Response Criteria for Malignant Lymphoma by Cheson et al., 2007, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study. |
| Measure Participants | 33 | 51 | 142 |
| Median (95% Confidence Interval) [days] |
657
|
183
|
NA
|
| Title | Functional Assessment of Cancer Therapy - Lymphoma Lymphoma Subscale (FACT-Lym LymS) at Week 16 - Part B |
|---|---|
| Description | HRQoL assessment was used to describe development of patients with copanlisib by using FACT-Lym questionnaire assessment tool. It contains 42 items (questions) covering HRQoL, common lymphoma symptoms and treatment side-effects. The FACT - General (FACT-G) questionnaire contains 27 items covering 4 core HRQoL subscales: Physical Wellbeing (7 items), Social/Family Wellbeing (7), Emotional Wellbeing (6), and Functional Wellbeing (7). The FACT-Lym also includes an Additional Concerns subscale (15 items) (FACT-Lym LymS), addressing issues typically experienced by lymphoma patients. Some of the issues covered include pain, itching, night sweats, trouble sleeping, fatigue and trouble concentrating. FACT-Lym also asks patients about lumps and swelling, fevers, infections, weight, appetite, emotional stability and treatment. Score range for the FACT-Lym LymS was 0 - 60, higher score represent less symptoms. Here in below table "n" signifies evaluable participants for the respective category. |
| Time Frame | Baseline up to the last patient has completed the 16 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all patients assigned to study treatment. The analysis was performed by using last observation carried forward (LOCF) method. |
| Arm/Group Title | Part B: Indolent NHL |
|---|---|
| Arm/Group Description | Participants with indolent B-cell NHL received copanlisib 60 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Revised Response Criteria for Malignant Lymphoma by Cheson et al., 2007, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study. |
| Measure Participants | 141 |
| Baseline |
46.50
|
| Value at Week 16 |
49.00
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part A: Indolent NHL/CLL |
|---|---|---|
| Comments | Hodges-Lehmann-estimate was used to calculate change to Week 16 and 95% confidence interval. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hodges-Lehmann-estimate |
| Estimated Value | 1.00 | |
| Confidence Interval |
(2-Sided) 95% 0.5 to 2.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Total Score at Week 16 - Part B |
|---|---|
| Description | HRQoL assessment was used to describe development of patients with copanlisib by using FACT-Lym questionnaire assessment tool. It contains 42 items (questions) covering HRQoL, common lymphoma symptoms and treatment side-effects. The FACT - General (FACT-G) questionnaire contains 27 items covering 4 core HRQoL subscales: Physical Wellbeing (7 items), Social/Family Wellbeing (7), Emotional Wellbeing (6), and Functional Wellbeing (7). The FACT-Lym also includes an Additional Concerns subscale (15 items) (FACT-Lym LymS), addressing issues typically experienced by lymphoma patients. Some of the issues covered include pain, itching, night sweats, trouble sleeping, fatigue and trouble concentrating. FACT-Lym also asks patients about lumps and swelling, fevers, infections, weight, appetite, emotional stability and treatment. FACT-Lym total score range was 0-168, higher score indicates better HRQoL. Here, in the below table "n" signifies evaluable participants for the respective category. |
| Time Frame | Baseline up to the last patient has completed the 16 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all patients assigned to study treatment. The analysis was performed by using last LOCF method. |
| Arm/Group Title | Part B: Indolent NHL |
|---|---|
| Arm/Group Description | Participants with indolent B-cell NHL received copanlisib 60 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Revised Response Criteria for Malignant Lymphoma by Cheson et al., 2007, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study. |
| Measure Participants | 141 |
| Baseline |
127.50
|
| Value at Week 16 |
130.83
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part A: Indolent NHL/CLL |
|---|---|---|
| Comments | Hodges-Lehmann-estimate was used to calculate change to Week 16 and 95% confidence interval. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hodges-Lehmann-estimate |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -0.5 to 3.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | From start of study treatment up to 35 days after the last dose of study medication, with updated AE data from FEB 2017. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Part A: Indolent NHL/CLL | Part A: Aggressive NHL | Part B: Indolent NHL | |||
| Arm/Group Description | Participants with indolent Non-Hodgkin's lymphoma/Chronic lymphocytic leukemia [iNHL/CLL] received copanlisib 0.8 milligram per kilogram (mg/kg), maximum 65 mg, intravenous (IV) infusion dosing over 1 hour in 100 milliliter (mL) normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study. | Participants with aggressive NHL (aNHL) received copanlisib 0.8 mg/kg, maximum 65 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas by Cheson et al. 1999, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study. | Participants with indolent B-cell NHL received copanlisib 60 mg, IV infusion dosing over 1 hour in 100 mL normal saline solution on Days 1, 8, and 15 of a 28-day treatment cycle until occurrence of progressive disease, as defined in the Revised Response Criteria for Malignant Lymphoma by Cheson et al., 2007, clinical progression, unacceptable toxicity, or any other criteria meeting withdrawal from study. | |||
All Cause Mortality |
||||||
| Part A: Indolent NHL/CLL | Part A: Aggressive NHL | Part B: Indolent NHL | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Part A: Indolent NHL/CLL | Part A: Aggressive NHL | Part B: Indolent NHL | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 14/33 (42.4%) | 31/51 (60.8%) | 74/142 (52.1%) | |||
| Blood and lymphatic system disorders | ||||||
| Febrile neutropenia | 1/33 (3%) | 1 | 2/51 (3.9%) | 3 | 3/142 (2.1%) | 3 |
| Leukocytosis | 1/33 (3%) | 1 | 0/51 (0%) | 0 | 0/142 (0%) | 0 |
| Neutropenia | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 4/142 (2.8%) | 5 |
| Pancytopenia | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Thrombotic thrombocytopenic purpura | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Autoimmune haemolytic anaemia | 1/33 (3%) | 1 | 0/51 (0%) | 0 | 0/142 (0%) | 0 |
| Cardiac disorders | ||||||
| Acute myocardial infarction | 0/33 (0%) | 0 | 1/51 (2%) | 1 | 0/142 (0%) | 0 |
| Aortic valve incompetence | 0/33 (0%) | 0 | 1/51 (2%) | 1 | 0/142 (0%) | 0 |
| Atrial fibrillation | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 2/142 (1.4%) | 2 |
| Ear and labyrinth disorders | ||||||
| Vertigo | 0/33 (0%) | 0 | 1/51 (2%) | 1 | 0/142 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Abdominal pain | 0/33 (0%) | 0 | 1/51 (2%) | 1 | 1/142 (0.7%) | 1 |
| Abdominal pain lower | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Colitis | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Diarrhoea | 0/33 (0%) | 0 | 3/51 (5.9%) | 3 | 4/142 (2.8%) | 4 |
| Gastritis | 0/33 (0%) | 0 | 2/51 (3.9%) | 2 | 0/142 (0%) | 0 |
| Gastrointestinal haemorrhage | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Melaena | 1/33 (3%) | 1 | 0/51 (0%) | 0 | 0/142 (0%) | 0 |
| Nausea | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 2/142 (1.4%) | 2 |
| Pancreatitis | 0/33 (0%) | 0 | 2/51 (3.9%) | 2 | 0/142 (0%) | 0 |
| Pancreatitis acute | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Stomatitis | 0/33 (0%) | 0 | 1/51 (2%) | 1 | 0/142 (0%) | 0 |
| Lower gastrointestinal haemorrhage | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Haemorrhoidal haemorrhage | 1/33 (3%) | 1 | 0/51 (0%) | 0 | 0/142 (0%) | 0 |
| General disorders | ||||||
| Fatigue | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Influenza like illness | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Pyrexia | 1/33 (3%) | 1 | 0/51 (0%) | 0 | 9/142 (6.3%) | 9 |
| General physical health deterioration | 1/33 (3%) | 1 | 4/51 (7.8%) | 4 | 2/142 (1.4%) | 2 |
| Multiple organ dysfunction syndrome | 0/33 (0%) | 0 | 1/51 (2%) | 1 | 0/142 (0%) | 0 |
| Hepatobiliary disorders | ||||||
| Cholangitis | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Cholecystitis | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Gallbladder obstruction | 0/33 (0%) | 0 | 1/51 (2%) | 1 | 0/142 (0%) | 0 |
| Infections and infestations | ||||||
| Bacteraemia | 1/33 (3%) | 1 | 0/51 (0%) | 0 | 0/142 (0%) | 0 |
| Bronchitis | 0/33 (0%) | 0 | 2/51 (3.9%) | 2 | 0/142 (0%) | 0 |
| Bronchopulmonary aspergillosis | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Cellulitis | 0/33 (0%) | 0 | 1/51 (2%) | 1 | 1/142 (0.7%) | 1 |
| Cryptococcosis | 1/33 (3%) | 1 | 0/51 (0%) | 0 | 0/142 (0%) | 0 |
| Herpes zoster | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Infection | 1/33 (3%) | 1 | 0/51 (0%) | 0 | 0/142 (0%) | 0 |
| Influenza | 0/33 (0%) | 0 | 1/51 (2%) | 1 | 0/142 (0%) | 0 |
| Lower respiratory tract infection | 0/33 (0%) | 0 | 3/51 (5.9%) | 3 | 0/142 (0%) | 0 |
| Pharyngitis | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Pneumonia | 1/33 (3%) | 1 | 3/51 (5.9%) | 4 | 16/142 (11.3%) | 19 |
| Pneumonia pneumococcal | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Pneumonia viral | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Progressive multifocal leukoencephalopathy | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Pyelonephritis | 0/33 (0%) | 0 | 2/51 (3.9%) | 2 | 1/142 (0.7%) | 1 |
| Sepsis | 0/33 (0%) | 0 | 2/51 (3.9%) | 2 | 1/142 (0.7%) | 1 |
| Septic shock | 0/33 (0%) | 0 | 1/51 (2%) | 1 | 2/142 (1.4%) | 2 |
| Sinusitis | 1/33 (3%) | 1 | 1/51 (2%) | 2 | 0/142 (0%) | 0 |
| Tooth abscess | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Urinary tract infection | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Rectal abscess | 0/33 (0%) | 0 | 1/51 (2%) | 1 | 0/142 (0%) | 0 |
| Sinusitis aspergillus | 0/33 (0%) | 0 | 1/51 (2%) | 1 | 0/142 (0%) | 0 |
| Corona virus infection | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Enterocolitis infectious | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Klebsiella bacteraemia | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Lung infection | 2/33 (6.1%) | 2 | 1/51 (2%) | 1 | 4/142 (2.8%) | 4 |
| Pneumonia fungal | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Respiratory tract infection | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 2 |
| Device related infection | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 2/142 (1.4%) | 2 |
| Pneumocystis jirovecii pneumonia | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 2/142 (1.4%) | 2 |
| Pneumocystis jirovecii infection | 0/33 (0%) | 0 | 1/51 (2%) | 1 | 0/142 (0%) | 0 |
| Systemic infection | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Injury, poisoning and procedural complications | ||||||
| Femur fracture | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Afferent loop syndrome | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Investigations | ||||||
| Neutrophil count decreased | 1/33 (3%) | 1 | 1/51 (2%) | 1 | 2/142 (1.4%) | 2 |
| Platelet count decreased | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Metabolism and nutrition disorders | ||||||
| Dehydration | 0/33 (0%) | 0 | 1/51 (2%) | 1 | 0/142 (0%) | 0 |
| Diabetes mellitus | 1/33 (3%) | 1 | 0/51 (0%) | 0 | 0/142 (0%) | 0 |
| Hypercalcaemia | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 2/142 (1.4%) | 2 |
| Hyperglycaemia | 1/33 (3%) | 1 | 0/51 (0%) | 0 | 7/142 (4.9%) | 9 |
| Musculoskeletal and connective tissue disorders | ||||||
| Back pain | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Groin pain | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Pain in extremity | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 2/142 (1.4%) | 2 |
| Psoriatic arthropathy | 0/33 (0%) | 0 | 1/51 (2%) | 2 | 0/142 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Basal cell carcinoma | 0/33 (0%) | 0 | 1/51 (2%) | 1 | 0/142 (0%) | 0 |
| Myelodysplastic syndrome | 0/33 (0%) | 0 | 1/51 (2%) | 1 | 0/142 (0%) | 0 |
| Plasma cell myeloma | 0/33 (0%) | 0 | 1/51 (2%) | 1 | 0/142 (0%) | 0 |
| Squamous cell carcinoma | 0/33 (0%) | 0 | 1/51 (2%) | 1 | 0/142 (0%) | 0 |
| Tumour flare | 0/33 (0%) | 0 | 1/51 (2%) | 1 | 0/142 (0%) | 0 |
| Tumour compression | 0/33 (0%) | 0 | 1/51 (2%) | 1 | 0/142 (0%) | 0 |
| Nervous system disorders | ||||||
| Seizure | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Syncope | 1/33 (3%) | 1 | 0/51 (0%) | 0 | 0/142 (0%) | 0 |
| Psychiatric disorders | ||||||
| Disorientation | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Renal and urinary disorders | ||||||
| Obstructive uropathy | 0/33 (0%) | 0 | 1/51 (2%) | 1 | 0/142 (0%) | 0 |
| Renal failure | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Urinary tract obstruction | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 2/142 (1.4%) | 2 |
| Renal impairment | 0/33 (0%) | 0 | 1/51 (2%) | 1 | 0/142 (0%) | 0 |
| Acute kidney injury | 1/33 (3%) | 1 | 0/51 (0%) | 0 | 2/142 (1.4%) | 2 |
| Reproductive system and breast disorders | ||||||
| Scrotal swelling | 0/33 (0%) | 0 | 1/51 (2%) | 1 | 0/142 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Acute respiratory failure | 1/33 (3%) | 1 | 1/51 (2%) | 1 | 0/142 (0%) | 0 |
| Dyspnoea | 0/33 (0%) | 0 | 1/51 (2%) | 1 | 1/142 (0.7%) | 1 |
| Epistaxis | 1/33 (3%) | 1 | 0/51 (0%) | 0 | 0/142 (0%) | 0 |
| Interstitial lung disease | 0/33 (0%) | 0 | 1/51 (2%) | 1 | 2/142 (1.4%) | 2 |
| Lung disorder | 1/33 (3%) | 1 | 1/51 (2%) | 1 | 0/142 (0%) | 0 |
| Pleural effusion | 1/33 (3%) | 1 | 0/51 (0%) | 0 | 0/142 (0%) | 0 |
| Pneumonitis | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 6/142 (4.2%) | 8 |
| Pulmonary congestion | 0/33 (0%) | 0 | 1/51 (2%) | 1 | 0/142 (0%) | 0 |
| Pulmonary embolism | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Pulmonary oedema | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 2 |
| Respiratory failure | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Organising pneumonia | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||
| Dermatitis exfoliative | 0/33 (0%) | 0 | 1/51 (2%) | 1 | 1/142 (0.7%) | 1 |
| Rash maculo-papular | 1/33 (3%) | 1 | 0/51 (0%) | 0 | 0/142 (0%) | 0 |
| Surgical and medical procedures | ||||||
| Preoperative care | 0/33 (0%) | 0 | 1/51 (2%) | 1 | 0/142 (0%) | 0 |
| Vascular disorders | ||||||
| Arteriovenous fistula | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Circulatory collapse | 0/33 (0%) | 0 | 1/51 (2%) | 1 | 0/142 (0%) | 0 |
| Hypertension | 1/33 (3%) | 1 | 0/51 (0%) | 0 | 0/142 (0%) | 0 |
| Thrombophlebitis superficial | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Deep vein thrombosis | 0/33 (0%) | 0 | 1/51 (2%) | 1 | 0/142 (0%) | 0 |
| Embolism | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||
| Part A: Indolent NHL/CLL | Part A: Aggressive NHL | Part B: Indolent NHL | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 33/33 (100%) | 50/51 (98%) | 138/142 (97.2%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 11/33 (33.3%) | 21 | 12/51 (23.5%) | 13 | 22/142 (15.5%) | 36 |
| Lymphopenia | 0/33 (0%) | 0 | 0/51 (0%) | 0 | 8/142 (5.6%) | 16 |
| Neutropenia | 9/33 (27.3%) | 12 | 15/51 (29.4%) | 25 | 37/142 (26.1%) | 86 |
| Thrombocytopenia | 3/33 (9.1%) | 3 | 3/51 (5.9%) | 3 | 20/142 (14.1%) | 24 |
| Ear and labyrinth disorders | ||||||
| Vertigo | 2/33 (6.1%) | 2 | 1/51 (2%) | 1 | 0/142 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Abdominal pain | 4/33 (12.1%) | 6 | 1/51 (2%) | 1 | 10/142 (7%) | 10 |
| Abdominal pain upper | 3/33 (9.1%) | 4 | 3/51 (5.9%) | 3 | 10/142 (7%) | 15 |
| Constipation | 5/33 (15.2%) | 7 | 8/51 (15.7%) | 11 | 18/142 (12.7%) | 20 |
| Diarrhoea | 13/33 (39.4%) | 65 | 21/51 (41.2%) | 39 | 48/142 (33.8%) | 86 |
| Dry mouth | 3/33 (9.1%) | 3 | 3/51 (5.9%) | 3 | 1/142 (0.7%) | 1 |
| Gastrooesophageal reflux disease | 2/33 (6.1%) | 2 | 2/51 (3.9%) | 2 | 5/142 (3.5%) | 5 |
| Nausea | 10/33 (30.3%) | 17 | 18/51 (35.3%) | 22 | 33/142 (23.2%) | 45 |
| Oral pain | 0/33 (0%) | 0 | 3/51 (5.9%) | 3 | 3/142 (2.1%) | 3 |
| Stomatitis | 4/33 (12.1%) | 6 | 4/51 (7.8%) | 4 | 12/142 (8.5%) | 21 |
| Vomiting | 5/33 (15.2%) | 10 | 5/51 (9.8%) | 7 | 19/142 (13.4%) | 23 |
| General disorders | ||||||
| Asthenia | 8/33 (24.2%) | 13 | 6/51 (11.8%) | 6 | 11/142 (7.7%) | 14 |
| Chest pain | 1/33 (3%) | 1 | 3/51 (5.9%) | 4 | 3/142 (2.1%) | 3 |
| Chills | 2/33 (6.1%) | 2 | 1/51 (2%) | 1 | 12/142 (8.5%) | 13 |
| Fatigue | 16/33 (48.5%) | 20 | 14/51 (27.5%) | 15 | 36/142 (25.4%) | 40 |
| Influenza like illness | 2/33 (6.1%) | 2 | 2/51 (3.9%) | 2 | 5/142 (3.5%) | 5 |
| Mucosal inflammation | 4/33 (12.1%) | 5 | 6/51 (11.8%) | 8 | 10/142 (7%) | 16 |
| Oedema peripheral | 3/33 (9.1%) | 7 | 2/51 (3.9%) | 2 | 11/142 (7.7%) | 13 |
| Pyrexia | 10/33 (30.3%) | 14 | 8/51 (15.7%) | 22 | 34/142 (23.9%) | 51 |
| Infections and infestations | ||||||
| Bronchitis | 4/33 (12.1%) | 9 | 5/51 (9.8%) | 8 | 14/142 (9.9%) | 19 |
| Conjunctivitis | 3/33 (9.1%) | 3 | 1/51 (2%) | 2 | 5/142 (3.5%) | 6 |
| Cystitis | 4/33 (12.1%) | 5 | 1/51 (2%) | 1 | 1/142 (0.7%) | 1 |
| Herpes zoster | 2/33 (6.1%) | 2 | 1/51 (2%) | 1 | 2/142 (1.4%) | 3 |
| Lower respiratory tract infection | 1/33 (3%) | 1 | 3/51 (5.9%) | 6 | 4/142 (2.8%) | 5 |
| Nasopharyngitis | 1/33 (3%) | 2 | 2/51 (3.9%) | 2 | 8/142 (5.6%) | 11 |
| Oral candidiasis | 0/33 (0%) | 0 | 3/51 (5.9%) | 3 | 6/142 (4.2%) | 7 |
| Rhinitis | 1/33 (3%) | 1 | 1/51 (2%) | 1 | 8/142 (5.6%) | 11 |
| Upper respiratory tract infection | 2/33 (6.1%) | 2 | 2/51 (3.9%) | 2 | 20/142 (14.1%) | 33 |
| Urinary tract infection | 6/33 (18.2%) | 6 | 7/51 (13.7%) | 7 | 7/142 (4.9%) | 7 |
| Lung infection | 2/33 (6.1%) | 2 | 2/51 (3.9%) | 2 | 4/142 (2.8%) | 4 |
| Oral herpes | 1/33 (3%) | 2 | 2/51 (3.9%) | 2 | 9/142 (6.3%) | 12 |
| Injury, poisoning and procedural complications | ||||||
| Procedural pain | 2/33 (6.1%) | 2 | 0/51 (0%) | 0 | 1/142 (0.7%) | 1 |
| Investigations | ||||||
| Blood creatinine increased | 1/33 (3%) | 1 | 4/51 (7.8%) | 5 | 4/142 (2.8%) | 4 |
| Blood glucose increased | 2/33 (6.1%) | 5 | 0/51 (0%) | 0 | 2/142 (1.4%) | 42 |
| Eosinophil count increased | 2/33 (6.1%) | 2 | 1/51 (2%) | 1 | 0/142 (0%) | 0 |
| Lipase increased | 2/33 (6.1%) | 4 | 2/51 (3.9%) | 2 | 7/142 (4.9%) | 8 |
| Neutrophil count decreased | 3/33 (9.1%) | 15 | 1/51 (2%) | 2 | 7/142 (4.9%) | 19 |
| Platelet count decreased | 5/33 (15.2%) | 5 | 4/51 (7.8%) | 4 | 11/142 (7.7%) | 14 |
| Weight decreased | 0/33 (0%) | 0 | 2/51 (3.9%) | 2 | 9/142 (6.3%) | 9 |
| Metabolism and nutrition disorders | ||||||
| Hyperglycaemia | 21/33 (63.6%) | 88 | 27/51 (52.9%) | 55 | 69/142 (48.6%) | 269 |
| Hypokalaemia | 2/33 (6.1%) | 3 | 5/51 (9.8%) | 5 | 10/142 (7%) | 10 |
| Hypomagnesaemia | 1/33 (3%) | 1 | 2/51 (3.9%) | 3 | 10/142 (7%) | 11 |
| Hypophosphataemia | 2/33 (6.1%) | 2 | 4/51 (7.8%) | 4 | 4/142 (2.8%) | 10 |
| Decreased appetite | 5/33 (15.2%) | 6 | 7/51 (13.7%) | 8 | 15/142 (10.6%) | 15 |
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 3/33 (9.1%) | 4 | 2/51 (3.9%) | 2 | 10/142 (7%) | 10 |
| Back pain | 2/33 (6.1%) | 4 | 4/51 (7.8%) | 4 | 14/142 (9.9%) | 18 |
| Muscle spasms | 7/33 (21.2%) | 10 | 3/51 (5.9%) | 5 | 11/142 (7.7%) | 15 |
| Musculoskeletal pain | 3/33 (9.1%) | 3 | 3/51 (5.9%) | 3 | 1/142 (0.7%) | 1 |
| Nervous system disorders | ||||||
| Dizziness | 3/33 (9.1%) | 4 | 3/51 (5.9%) | 4 | 4/142 (2.8%) | 5 |
| Dysgeusia | 3/33 (9.1%) | 3 | 2/51 (3.9%) | 2 | 4/142 (2.8%) | 4 |
| Headache | 7/33 (21.2%) | 9 | 9/51 (17.6%) | 12 | 13/142 (9.2%) | 21 |
| Neuropathy peripheral | 1/33 (3%) | 1 | 3/51 (5.9%) | 3 | 6/142 (4.2%) | 6 |
| Paraesthesia | 3/33 (9.1%) | 3 | 1/51 (2%) | 1 | 4/142 (2.8%) | 5 |
| Somnolence | 2/33 (6.1%) | 2 | 0/51 (0%) | 0 | 0/142 (0%) | 0 |
| Psychiatric disorders | ||||||
| Anxiety | 0/33 (0%) | 0 | 3/51 (5.9%) | 3 | 4/142 (2.8%) | 5 |
| Insomnia | 0/33 (0%) | 0 | 3/51 (5.9%) | 3 | 8/142 (5.6%) | 8 |
| Renal and urinary disorders | ||||||
| Dysuria | 2/33 (6.1%) | 2 | 0/51 (0%) | 0 | 2/142 (1.4%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 6/33 (18.2%) | 12 | 6/51 (11.8%) | 6 | 27/142 (19%) | 37 |
| Dyspnoea | 4/33 (12.1%) | 4 | 4/51 (7.8%) | 4 | 11/142 (7.7%) | 11 |
| Dyspnoea exertional | 3/33 (9.1%) | 3 | 1/51 (2%) | 1 | 4/142 (2.8%) | 4 |
| Epistaxis | 2/33 (6.1%) | 4 | 3/51 (5.9%) | 3 | 0/142 (0%) | 0 |
| Nasal congestion | 2/33 (6.1%) | 3 | 0/51 (0%) | 0 | 4/142 (2.8%) | 5 |
| Productive cough | 3/33 (9.1%) | 3 | 3/51 (5.9%) | 3 | 9/142 (6.3%) | 11 |
| Rhinorrhoea | 2/33 (6.1%) | 2 | 2/51 (3.9%) | 3 | 4/142 (2.8%) | 5 |
| Oropharyngeal pain | 1/33 (3%) | 1 | 2/51 (3.9%) | 2 | 13/142 (9.2%) | 18 |
| Skin and subcutaneous tissue disorders | ||||||
| Dry skin | 1/33 (3%) | 1 | 3/51 (5.9%) | 3 | 7/142 (4.9%) | 10 |
| Eczema | 3/33 (9.1%) | 4 | 2/51 (3.9%) | 2 | 3/142 (2.1%) | 5 |
| Erythema | 3/33 (9.1%) | 3 | 3/51 (5.9%) | 3 | 3/142 (2.1%) | 4 |
| Hyperhidrosis | 2/33 (6.1%) | 2 | 1/51 (2%) | 1 | 0/142 (0%) | 0 |
| Pruritus | 3/33 (9.1%) | 3 | 3/51 (5.9%) | 5 | 13/142 (9.2%) | 30 |
| Rash | 5/33 (15.2%) | 6 | 6/51 (11.8%) | 8 | 14/142 (9.9%) | 25 |
| Vascular disorders | ||||||
| Hypertension | 23/33 (69.7%) | 93 | 24/51 (47.1%) | 82 | 42/142 (29.6%) | 183 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Contract Partners (PI) shall provide to Bayer any proposed publication or oral presentation relating to the Study or the Results ("Publication") at least sixty (60) days prior to the intended submission or presentation of the Publication in order to allow Bayer to review it. If Bayer does not notify PI within forty-five (45) days of Bayer's receipt of the intended Publication, PI shall remind Bayer. If Bayer does not provide any comments within the sixty day period, PI shall be free to publish.
Results Point of Contact
| Name/Title | Therapeutic Area Head |
|---|---|
| Organization | Bayer |
| Phone | +1-888-8422937 |
| clinical-trials-contact@bayer.com |
Responsible Party:
Bayer
ClinicalTrials.gov Identifier:
NCT01660451
Other Study ID Numbers:
- 16349
- 2012-002602-52
First Posted:
Aug 8, 2012
Last Update Posted:
Feb 24, 2022
Last Verified:
Jan 1, 2022