Clinical trial NCT01410513: Study Combining SAR245409 With Rituximab or Bendamustine Plus Rituximab in Patients With Indolent Lymphoma, Mantle Cell Lymphoma and Chronic Lymphocytic Leukemia
Official title: A Phase 1b, Multicenter, Open-Label, Dose Escalation Study of SAR245409 to Evaluate the Safety, Tolerability and Clinical Activity of SAR245409 in Combination With Rituximab or Bendamustine Plus Rituximab in Patients With Relapsed or Refractory Indolent B-cell Non-Hodgkin Lymphoma, Mantle Cell Lymphoma or Chronic Lymphocytic Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Indolent Non-Hodgkin Lymphoma
Mantle Cell Lymphoma
Chronic Lymphocytic Leukemia
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2011-08-05
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary Objective:

- To determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) for SAR245409 when administered in combination with rituximab or bendamustine plus rituximab

Secondary Objectives:

* To determine the safety and tolerability of SAR245409 in combination with rituximab or bendamustine plus rituximab in subjects with indolent Hon-Hodgkin Lymphoma (iNHL) Mantle Cell Lymphoma (MCL) or Chronic Lymphocytic Leukemia (CLL)
* To determine the pharmacokinetics (PK) of SAR245409, bendamustine and rituximab when used in combination in subjects with iNHL, MCL or CLL
* To determine the pharmacodynamic (PD) effects of SAR245409 in combination with rituximab or bendamustine plus rituximab in subjects with iNHL, MCL or CLL
* To determine the antitumor activity of SAR245409 in combination with rituximab or bendamustine plus rituximab in subjects with iNHL, MCL or CLL

Detailed description: All subjects will take SAR245409 twice daily. All subjects will receive SAR245409 as long as there is clinical benefit.

Combination therapy with SAR245409, bendamustine and rituximab , will be administered over a 28 day cycle for up to 6 to 8 cycles.

Subjects receiving the doublet combination , SAR245409 plus rituximab will receive weekly rituximab for 4 - 8 weeks. Monthly Rituximab may be continued beyond 8 weeks.

Eligibility criteria: Inclusion criteria:

* A confirmed diagnosis of indolent non-Hodgkin lymphoma, mantle cell lymphoma or chronic lymphocytic leukemia
* Evaluable disease or measurable disease
* Transfusion independent
* Able to take oral medication
* Male and Female subjects \> 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
* Women of childbearing potential using adequate contraception

Exclusion criteria:

* Prior therapy with a PI3K, mTOR or dual PI3K/mTOR inhibitor resulting in adverse events necessitating treatment discontinuation
* Eligible for a hematopoietic stem cell transplant (HSCT)
* The subject has received investigational or non-investigational cytotoxic chemotherapy (i.e., cyclophosphamide), small molecule cancer therapy (i.e., imatinib), biologic cancer therapies other than rituximab (i.e., alemtuzumab, cytokines, vaccines or other monoclonal antibodies) hormonal therapy, radio- or immuno- conjugates (e.g. ibritumomab tiuxetan, tositumomab) or immunosuppressants to treat malignancy within 4 weeks prior to Cycle 1, Day 1
* Radiation therapy within 2 weeks prior to Cycle 1, Day 1
* Autologous Hematopoietic Stem Cell Transplant (HSCT) within the past 16 weeks
* Prior allogeneic HSCT
* Active central nervous system (CNS) metastases or leptomeningeal involvement
* Positive Hepatitis B surface antigen (HBsAg) or Hepatitis C Antibody (anti-HCV)
* Hereditary or acquired immunodeficiency syndrome or human immunodeficiency virus (HIV) infection
* Active peptic ulcer disease requiring treatment with proton pump inhibitors (e.g. pantoprazole) or Type 2 histamine antagonists (e.g. cimetidine)
* Diagnosis or treatment for another malignancy within 3 years of enrollment with the exception of complete resection of basal cell or squamous cell carcinoma of the skin, an in situ malignancy or low-risk prostate cancer after curative therapy
* Inadequate bone marrow function
* Abnormal liver function
* Abnormal renal function
* Abnormal coagulation

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Primary outcomes:
measure: Identification Of Dose-Limiting Toxicity (DLT) and Maximum Tolerated Dose (MTD)
timeFrame: 4 weeks to 8 weeks
Secondary outcomes:
measure: Number of subjects with treatment emergent adverse events
timeFrame: Time from receiving first dose of SAR245409 until 30 days after the last dose
measure: Pharmacokinetics (Cmax) of SAR245409
timeFrame: up to 2 months
measure: Pharmacokinetics (tmax) of SAR245409
timeFrame: up to 2 months
measure: Pharmacokinetics (AUC0-12h) of SAR245409
timeFrame: up to 2 months
measure: Pharmacokinetics (Ctrough) of SAR245409
timeFrame: up to 2 months
measure: Pharmacokinetics (AUC) of bendamustine
timeFrame: up to 2 months
measure: Pharmacokinetics (AUClast) of bendamustine
timeFrame: up to 2 months
measure: Pharmacokinetics (Ceoi) of bendamustine
timeFrame: up to 2 months
measure: Pharmacokinetics (tmax) of bendamustine
timeFrame: up to 2 months
measure: Pharmacokinetics (Cl) of bendamustine
timeFrame: up to 2 months
measure: Pharmacokinetics (Vss) of bendamustine
timeFrame: up to 2 months
measure: Pharmacokinetics (AUC0-7h) of rituximab
timeFrame: up to 2 months
measure: Pharmacokinetics (Ceoi) of rituximab
timeFrame: up to 2 months
measure: Pharmacokinetics (tmax) of rituximab
timeFrame: up to 2 months
measure: Efficacy as determined by objective response rate (ORR)
timeFrame: up to 4 years
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Investigational Site Number 840004
state: Colorado
city: Augusta
country: United States
facility: Investigational Site Number 840006
state: Georgia
city: Charleston
country: United States
facility: Investigational Site Number 840002
state: South Carolina
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: