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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Sanofi
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01410513
First received: July 26, 2011
Last updated: July 22, 2014
Last verified: July 2014
  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
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: 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 Subjects 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 ] [ Designated as safety issue: Yes ]

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 ] [ Designated as safety issue: No ]
  • Pharmacokinetics (Cmax) of SAR245409 [ Time Frame: up to 2 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics (tmax) of SAR245409 [ Time Frame: up to 2 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics (AUC0-12h) of SAR245409 [ Time Frame: up to 2 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics (Ctrough) of SAR245409 [ Time Frame: up to 2 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics (AUC) of bendamustine [ Time Frame: up to 2 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics (AUClast) of bendamustine [ Time Frame: up to 2 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics (Ceoi) of bendamustine [ Time Frame: up to 2 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics (tmax) of bendamustine [ Time Frame: up to 2 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics (Cl) of bendamustine [ Time Frame: up to 2 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics (Vss) of bendamustine [ Time Frame: up to 2 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics (AUC0-7h) of rituximab [ Time Frame: up to 2 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics (Ceoi) of rituximab [ Time Frame: up to 2 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics (tmax) of rituximab [ Time Frame: up to 2 months ] [ Designated as safety issue: No ]
  • Efficacy as determined by objective response rate (ORR) [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 85
Study Start Date: December 2011
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01410513

Contacts
Contact: For site information, send an email with site number to Contact-Us@sanofi.com

Locations
United States, Colorado
Investigational Site Number 840004 Completed
Aurora, Colorado, United States, 80045
United States, Georgia
Investigational Site Number 840006 Completed
Augusta, Georgia, United States, 30912
United States, South Carolina
Investigational Site Number 840002 Completed
Charleston, South Carolina, United States, 29406
United States, Texas
Investigational Site Number 840003 Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01410513     History of Changes
Other Study ID Numbers: TCD12012, U1111-1119-2906
Study First Received: July 26, 2011
Last Updated: July 22, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bendamustine
Rituximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on July 28, 2014