We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01410513
First Posted: August 5, 2011
Last Update Posted: April 1, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Sanofi
  Purpose

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

Condition Intervention Phase
Indolent Non-Hodgkin Lymphoma Mantle Cell Lymphoma Chronic Lymphocytic Leukemia Drug: SAR245409 Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Identification Of Dose-Limiting Toxicity (DLT) and Maximum Tolerated Dose (MTD) [ Time Frame: 4 weeks to 8 weeks ]

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

Enrollment: 37
Study Start Date: December 2011
Study Completion Date: May 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01410513


Locations
United States, Colorado
Investigational Site Number 840004
Aurora, Colorado, United States, 80045
United States, Georgia
Investigational Site Number 840006
Augusta, Georgia, United States, 30912
United States, South Carolina
Investigational Site Number 840002
Charleston, South Carolina, United States, 29406
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01410513     History of Changes
Other Study ID Numbers: TCD12012
U1111-1119-2906 ( Other Identifier: UTN )
First Submitted: July 26, 2011
First Posted: August 5, 2011
Last Update Posted: April 1, 2016
Last Verified: September 2014

Additional relevant MeSH terms:
Lymphoma
Leukemia
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Rituximab
Bendamustine Hydrochloride
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action