Phase II PI3K inhibitor in relapsed, indolent or aggressive NH

Phase 1

• Conditions: Patients with relapsed, indolent or aggressive Non-Hodgkin’s lymphomas or patients with follicular lymphoma relapsed after or refractory to standard therapy.; MedDRA version: 21.1Level: PTClassification code 10029600Term: Non-Hodgkin's lymphoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: HLTClassification code 10029621Term: Non-Hodgkin's lymphomas unspecified histology indolentSystem Organ Class: 100000004851; MedDRA version: 20.0Level: HLTClassification code 10029608Term: Non-Hodgkin's lymphomas unspecified histology aggressiveSystem Organ Class: 100000004851; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-002602-52-GB
• Lead Sponsor: Bayer AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2012-08-07
• Last Update Posted: 27 July 2020

Recruitment & Eligibility

• Status: ot Recruiting
• 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, 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.

For all patients:
• Ability to understand and willingness to sign written informed consent (IC). Signed informed consent must be obtained before any study specific procedure.
• Male or female patients > 18 years of age.
• Patients must have at least one measurable lesion (that has not been previously irradiated) according to the recommendations of the Revised Reponse Criteria for Malignant Lymphoma.
• Availability of archival and/or fresh tumor tissue
• ECOG performance status = 2.
• Life expectancy of at least 3 months.
• Women of childbearing potential and men must agree to use adequate contraception since signing of the informed consent form until at least 3 months after the last test drug administration. The investigator or a designated associate is requested to advise the patient how to achieve an adequate birth control. Adequate contraception is defined in the study as any medically recommended method (or combination of methods) as per standard of care. An adequate contraception includes a hormonal contraception with implants or combined oral, transdermal or injectable contraceptives, certain intrauterine devices, bilateral tubal ligation, hysterectomy, or vasectomy of the partner. In addition the use of condoms for patients or their partners is required unless the woman has had a hysterectomy.
• Adequate bone marrow, liver and renal function as assessed by laboratory requirements conducted within 7 days before starting study treatment.
• Left ventricular ejection fraction (LVEF) = lower limit of normal (LLN) for the Institution

Applicable to all patients in 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 absol

Exclusion Criteria

Patients who meet any of the following criteria at the time of screening will be excluded:
Excluded medical conditions:
• Previous or concurrent cancer that is distinct in primary site or histology from non-Hodkin's lymphoma within 5 years prior to treatment start EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)].
• Known lymphomatous involvement of the central nervous system.
• Congestive heart failure > New York Heart Association (NYHA) class 2.
• Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months). Myocardial infarction less than 6 months before start of test drug.
• Uncontrolled hypertension.
• Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months before start of study medication.
• Non-healing wound, ulcer, or bone fracture.
• Active clinically serious infections (> CTCAE grade 2).
• 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.
• Patients with seizure disorder requiring medication.
• Patients with evidence or history of bleeding diathesis.
• Renal failure requiring hemo-or peritoneal dialysis.
• Proteinuria of CTCAE grade 3 or higher: urine protein: creatinine ratio >3.5 on a random urine sample.
• Known hypersensitivity to any of the test drugs, test drug classes, or excipients in the formulation.
• 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.
• Current diagnosis of Type 1 or 2 diabetes mellitus, fasting blood glucose > 125 mg/dL (> 6.9 mmol/L) or HbA1c = 7.0 %
• Concurrent diagnosis of phaeochromocytoma.
• Pregnant or breast-feeding patients. Women of childbearing potential must have a pregnancy test performed a maximum of 7 days before start of treatment, and a negative result must be documented before start of treatment.

Excluded previous therapies and medications:
• Prior treatment with PI3K inhibitors.
• Treatment with investigational drugs other than PI3K inhibitors within 28 days prior to treatment start.
• Ongoing immunosuppressive therapy.
• Radiotherapy within 4 weeks prior to treatment start.
• Myeloid growth factors within 14 days prior to treatment start.
• Blood or platelet transfusion within 14 days prior to treatment start.
• Systemic corticosteroid therapy (ongoing). Previous corticosteroids therapy must be stopped within 7 days prior to first study drug administration. Patients may be using topical or inhaled corticosteroids.
• History of having received an allogeneic bone marrow or organ transplant
• Major surgical procedure, or significant traumatic injury within 28 days before start of study medication; open biopsy within 7 days before start of study medication.
• Cardiac arrhythmias requiring anti-arrhythmic therapy (

Study & Design

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