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

NCT01410513 | Completed Phase 1

• 2 other identifiers: TCD12012U1111-1119-2906
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 3

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

Conditions

Indolent Non-Hodgkin Lymphoma; Mantle Cell Lymphoma; Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Identification Of Dose-Limiting Toxicity (DLT) and Maximum Tolerated Dose (MTD)

  4 weeks to 8 weeks

Secondary Outcomes (15)

• 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

Study Arms (3)

SAR245409 + rituximab

EXPERIMENTAL

Subjects will receive oral SAR245409 twice daily continuously and weekly rituximab intravenously

Drug: SAR245409

SAR245409 + rituximab + bendamustine (iNHL, MCL)

EXPERIMENTAL

Subjects will receive oral SAR245409 twice daily continuously and monthly bendamustine intravenously.

Drug: SAR245409

SAR245409 + rituximab+ bendamustine (CLL)

EXPERIMENTAL

Subjects will receive oral SAR245409 twice daily continuously and monthly bendamustine and rituximab intravenously

Drug: SAR245409

Interventions

SAR245409 DRUG

Pharmaceutical form:capsule Route of administration: oral

SAR245409 + rituximab; SAR245409 + rituximab + bendamustine (iNHL, MCL); SAR245409 + rituximab+ bendamustine (CLL)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sanofi: lead

Study Sites (3)

Investigational Site Number 840004

Aurora, Colorado, 80045, United States

Location

Investigational Site Number 840006

Augusta, Georgia, 30912, United States

Location

Investigational Site Number 840002

Charleston, South Carolina, 29406, United States

Location

MeSH Terms

Conditions

Lymphoma, Mantle-Cell; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

XL765

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2011
• First Posted: August 5, 2011
• Study Start: December 1, 2011
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: April 1, 2016

Record last verified: 2014-09

Locations

US (3)