Open-label, Uncontrolled Phase II Trial of Intravenous PI3K Inhibitor BAY80-6946 in Patients With Relapsed, Indolent or Aggressive Non-Hodgkin's Lymphomas
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Lymphoma |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 3/23/2019 |
| Start Date: | November 19, 2012 |
| End Date: | March 8, 2020 |
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.
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.
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)].
We found this trial at
16
sites
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials