Phase II PI3K inhibitor in relapsed, indolent or aggressive NH

Conditions: Patients with relapsed, indolent or aggressive Non- Hodgkin’s lymphomas or patients with indolent B-cell Non-Hodgkin's lymphoma relapsed after or refractory to standard therapy.
MedDRA version: 18.0Level: PTClassification code 10029600Term: Non-Hodgkin's lymphoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2012-002602-52-GR

Lead Sponsor: Bayer HealthCare AG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 330

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
- Availability of fresh tumor tissue
Indolent B-cell NHL lymphoma (study part B):
- Histologically confirmed diagnosis of indolent B-cell NHL, with histological subtype limited to the following:
o Follicular lymphoma (FL) grade 1-2-3a
o Small lymphocytic lymphoma (SLL) with absolute lymphocyte count < 5 x 109/L at the time of diagnosis and at study entry
o Lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM)
o Marginal zone lymphoma (MZL) (splenic, nodal, or 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 and/or fresh tumor tissue
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 190
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 140

Exclusion Criteria

For Part A:
-Uncontrolled hypertension (blood pressure = 150/90 mmHg despite optimal medical management)
-Current diagnosis of Type 1 or 2 diabetes mellitus, fasting blood glucose > 125 mg/dL (> 6.9 mmol/L) or HbA1c = 7.0 % (HbA1c: glycated hemoglobin)
- 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 or severely impaired pulmonary function (as judged by the investigator).
- 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
- 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 or severely impaired pulmonary function (as judged by the investigator)
- 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)
- Type I or II diabetes mellitus with HbA1c > 8.5% or fasting plasma glucose > 160 mg/dL at Screening
- Known history of human immunodeficiency virus (HIV) infection.
- 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.
- Known lymphomatous involvement of the central nervous system