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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01660451




Registration number
NCT01660451
Ethics application status
Date submitted
6/08/2012
Date registered
8/08/2012
Date last updated
28/06/2023

Titles & IDs
Public title
Open-label, Uncontrolled Phase II Trial of Intravenous PI3K Inhibitor BAY80-6946 in Patients With Relapsed, Indolent or Aggressive Non-Hodgkin's Lymphomas
Scientific title
Open-label, Uncontrolled Phase II Trial of Intravenous PI3K Inhibitor BAY80-6946 in Patients With Relapsed, Indolent or Aggressive Non-Hodgkin's Lymphomas
Secondary ID [1] 0 0
2012-002602-52
Secondary ID [2] 0 0
16349
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lymphoma, Non-Hodgkin 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Copanlisib (Aliqopa, BAY80-6946)

Experimental: Copanlisib (indolent NHL) - Part A: Participants in this arm will be patients with indolent NHL.

Experimental: Copanlisib (aggressive NHL) - Part A: Participants in this arm will be patients with aggressive NHL.

Experimental: Copanlisib (indolent B-cell NHL) - Part B: Participants in this arm will be patients with indolent B-cell NHL.


Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate (ORR) Based on Independent Review-Part A
Timepoint [1] 0 0
Baseline up to the last patient has completed the 16 weeks of treatment
Primary outcome [2] 0 0
Objective Response Rate (ORR) Based on Independent Review-Part B
Timepoint [2] 0 0
Baseline up to the last patient has completed the 16 weeks of treatment
Primary outcome [3] 0 0
ORR Based on Investigator Assessment-Part A
Timepoint [3] 0 0
Baseline up to the last patient has completed the 16 weeks of treatment
Primary outcome [4] 0 0
ORR Based on Investigator Assessment-Part B
Timepoint [4] 0 0
Baseline up to the last patient has completed the 16 weeks of treatment
Secondary outcome [1] 0 0
Duration of Response (DOR) Based on Independent Review
Timepoint [1] 0 0
Baseline up to the last patient has completed the 16 weeks of treatment
Secondary outcome [2] 0 0
DOR Based on Investigator Assessment
Timepoint [2] 0 0
Baseline up to the last patient has completed the 16 weeks of treatment
Secondary outcome [3] 0 0
Progression Free Survival (PFS) Based on Independent Review
Timepoint [3] 0 0
Baseline up to the last patient has completed the 16 weeks of treatment
Secondary outcome [4] 0 0
PFS Based on Investigator Assessment
Timepoint [4] 0 0
Baseline up to the last patient has completed the 16 weeks of treatment
Secondary outcome [5] 0 0
Overall Survival (OS)
Timepoint [5] 0 0
Baseline up to the last patient has completed the 16 weeks of treatment
Secondary outcome [6] 0 0
Functional Assessment of Cancer Therapy - Lymphoma Lymphoma Subscale (FACT-Lym LymS) at Week 16 - Part B
Timepoint [6] 0 0
Baseline up to the last patient has completed the 16 weeks of treatment
Secondary outcome [7] 0 0
Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Total Score at Week 16 - Part B
Timepoint [7] 0 0
Baseline up to the last patient has completed the 16 weeks of treatment

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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)].

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/11/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
18/05/2023
Sample size
Target
Accrual to date
Final
227
Recruitment in Australia
Recruitment state(s)
ACT
Recruitment hospital [1] 0 0
- Garran
Recruitment postcode(s) [1] 0 0
2605 - Garran
Recruitment outside Australia
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United States of America
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Alabama
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Arizona
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Washington
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Austria
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Linz
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Belgium
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Anderlecht
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Belgium
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Bruxelles - Brussel
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Gent
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Leuven
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Turnhout
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Wilrijk
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Sofia
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New Brunswick
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Canada
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Quebec
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Finland
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Helsinki
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Finland
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Oulu
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Tampere
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Finland
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Turku
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France
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Brest
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France
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Creteil
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France
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La Roche Sur Yon
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France
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Lille
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PARIS cedex
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France
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Pessac
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France
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Pierre Benite
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Poitiers
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Rouen
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Bayern
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Berlin
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Germany
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Sachsen
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Shatin
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Petach Tikva
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Italy
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Piemonte
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Kemerovo
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Valencia
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Istanbul
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Izmir
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Devon
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Hampshire
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London
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United Kingdom
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Merseyside
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Surrey
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United Kingdom
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West Midlands
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United Kingdom
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Leeds
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United Kingdom
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Manchester
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United Kingdom
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Romford

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Bayer
Address
Country

Ethics approval
Ethics application status

Summary
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 completed treatment. Patients who
discontinue study drug for reasons other than disease progression will enter the Active
Assessment Follow-up period. 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01660451
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bayer Study Director
Address 0 0
Bayer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01660451