Study Combining SAR245409 With Rituximab or Bendamustine Plus Rituximab in Patients With Indolent Lymphoma, Mantle Cell Lymphoma and Chronic Lymphocytic Leukemia

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

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

Study Overview

• Status: Completed
• Conditions: Mantle Cell Lymphoma; Chronic Lymphocytic Leukemia; Indolent Non-Hodgkin Lymphoma
• Intervention / Treatment: Drug: SAR245409

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.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Investigational Site Number 840004
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Investigational Site Number 840006
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Investigational Site Number 840002

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: SAR245409 + rituximab; Subjects will receive oral SAR245409 twice daily continuously and weekly rituximab intravenously	Drug: SAR245409; Pharmaceutical form:capsule Route of administration: oral
EXPERIMENTAL: SAR245409 + rituximab + bendamustine (iNHL, MCL); Subjects will receive oral SAR245409 twice daily continuously and monthly bendamustine intravenously.	Drug: SAR245409; Pharmaceutical form:capsule Route of administration: oral
EXPERIMENTAL: SAR245409 + rituximab+ bendamustine (CLL); Subjects will receive oral SAR245409 twice daily continuously and monthly bendamustine and rituximab intravenously	Drug: SAR245409; Pharmaceutical form:capsule Route of administration: oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Identification Of Dose-Limiting Toxicity (DLT) and Maximum Tolerated Dose (MTD)	4 weeks to 8 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of subjects with treatment emergent adverse events	Time from receiving first dose of SAR245409 until 30 days after the last dose
Pharmacokinetics (Cmax) of SAR245409	up to 2 months
Pharmacokinetics (tmax) of SAR245409	up to 2 months
Pharmacokinetics (AUC0-12h) of SAR245409	up to 2 months
Pharmacokinetics (Ctrough) of SAR245409	up to 2 months
Pharmacokinetics (AUC) of bendamustine	up to 2 months
Pharmacokinetics (AUClast) of bendamustine	up to 2 months
Pharmacokinetics (Ceoi) of bendamustine	up to 2 months
Pharmacokinetics (tmax) of bendamustine	up to 2 months
Pharmacokinetics (Cl) of bendamustine	up to 2 months
Pharmacokinetics (Vss) of bendamustine	up to 2 months
Pharmacokinetics (AUC0-7h) of rituximab	up to 2 months
Pharmacokinetics (Ceoi) of rituximab	up to 2 months
Pharmacokinetics (tmax) of rituximab	up to 2 months
Efficacy as determined by objective response rate (ORR)	up to 4 years

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (ACTUAL): May 1, 2014
• Study Completion (ACTUAL): May 1, 2014

Study Registration Dates

• First Submitted: July 26, 2011
• First Submitted That Met QC Criteria: August 4, 2011
• First Posted (ESTIMATE): August 5, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): April 1, 2016
• Last Update Submitted That Met QC Criteria: March 31, 2016
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, B-Cell; Lymphoma; Leukemia; Lymphoma, Non-Hodgkin; Lymphoma, Mantle-Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid
• Other Study ID Numbers: TCD12012; U1111-1119-2906 (OTHER: UTN)