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

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ClinicalTrials.gov Identifier: NCT01410513
Recruitment Status : Completed
First Posted : August 5, 2011
Last Update Posted : April 1, 2016
Sponsor:
Information provided by (Responsible Party):
Sanofi

Tracking Information
First Submitted Date  ICMJE July 26, 2011
First Posted Date  ICMJE August 5, 2011
Last Update Posted Date April 1, 2016
Study Start Date  ICMJE December 2011
Actual Primary Completion Date May 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 4, 2011)
Identification Of Dose-Limiting Toxicity (DLT) and Maximum Tolerated Dose (MTD) [ Time Frame: 4 weeks to 8 weeks ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 4, 2011)
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study Combining SAR245409 With Rituximab or Bendamustine Plus Rituximab in Patients With Indolent Lymphoma, Mantle Cell Lymphoma and Chronic Lymphocytic Leukemia
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Indolent Non-Hodgkin Lymphoma
  • Mantle Cell Lymphoma
  • Chronic Lymphocytic Leukemia
Intervention  ICMJE Drug: SAR245409
Pharmaceutical form:capsule Route of administration: oral
Study Arms  ICMJE
  • Experimental: SAR245409 + rituximab
    Subjects will receive oral SAR245409 twice daily continuously and weekly rituximab intravenously
    Intervention: Drug: SAR245409
  • Experimental: SAR245409 + rituximab + bendamustine (iNHL, MCL)
    Subjects will receive oral SAR245409 twice daily continuously and monthly bendamustine intravenously.
    Intervention: Drug: SAR245409
  • Experimental: SAR245409 + rituximab+ bendamustine (CLL)
    Subjects will receive oral SAR245409 twice daily continuously and monthly bendamustine and rituximab intravenously
    Intervention: Drug: SAR245409
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 31, 2016)
37
Original Estimated Enrollment  ICMJE
 (submitted: August 4, 2011)
85
Actual Study Completion Date  ICMJE May 2014
Actual Primary Completion Date May 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01410513
Other Study ID Numbers  ICMJE TCD12012
U1111-1119-2906 ( Other Identifier: UTN )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sanofi
Study Sponsor  ICMJE Sanofi
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Sciences & Operations Sanofi
PRS Account Sanofi
Verification Date September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP