Back to resultsStudy Combining SAR245409 With Rituximab or Bendamustine Plus Rituximab in Patients With Indolent Lymphoma, Mantle Cell Lymphoma and Chronic Lymphocytic Leukemia
Primary Purpose
Indolent Non-Hodgkin Lymphoma, Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
SAR245409
Sponsored by
About this trial
This is an interventional treatment trial for Indolent Non-Hodgkin Lymphoma
Eligibility 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.
Sites / Locations
- Investigational Site Number 840004
- Investigational Site Number 840006
- Investigational Site Number 840002
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
SAR245409 + rituximab
SAR245409 + rituximab + bendamustine (iNHL, MCL)
SAR245409 + rituximab+ bendamustine (CLL)
Arm Description
Subjects will receive oral SAR245409 twice daily continuously and weekly rituximab intravenously
Subjects will receive oral SAR245409 twice daily continuously and monthly bendamustine intravenously.
Subjects will receive oral SAR245409 twice daily continuously and monthly bendamustine and rituximab intravenously
Outcomes
Primary Outcome Measures
Identification Of Dose-Limiting Toxicity (DLT) and Maximum Tolerated Dose (MTD)
Secondary Outcome Measures
Number of subjects with treatment emergent adverse events
Pharmacokinetics (Cmax) of SAR245409
Pharmacokinetics (tmax) of SAR245409
Pharmacokinetics (AUC0-12h) of SAR245409
Pharmacokinetics (Ctrough) of SAR245409
Pharmacokinetics (AUC) of bendamustine
Pharmacokinetics (AUClast) of bendamustine
Pharmacokinetics (Ceoi) of bendamustine
Pharmacokinetics (tmax) of bendamustine
Pharmacokinetics (Cl) of bendamustine
Pharmacokinetics (Vss) of bendamustine
Pharmacokinetics (AUC0-7h) of rituximab
Pharmacokinetics (Ceoi) of rituximab
Pharmacokinetics (tmax) of rituximab
Efficacy as determined by objective response rate (ORR)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01410513
Brief Title
Study Combining SAR245409 With Rituximab or Bendamustine Plus Rituximab in Patients With Indolent Lymphoma, Mantle Cell Lymphoma and Chronic Lymphocytic Leukemia
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2014
Overall Recruitment Status
Completed
Study Start Date
December 2011 (undefined)
Primary Completion Date
May 2014 (Actual)
Study Completion Date
May 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Indolent Non-Hodgkin Lymphoma, Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
37 (Actual)
8. Arms, Groups, and Interventions
Arm Title
SAR245409 + rituximab
Arm Type
Experimental
Arm Description
Subjects will receive oral SAR245409 twice daily continuously and weekly rituximab intravenously
Arm Title
SAR245409 + rituximab + bendamustine (iNHL, MCL)
Arm Type
Experimental
Arm Description
Subjects will receive oral SAR245409 twice daily continuously and monthly bendamustine intravenously.
Arm Title
SAR245409 + rituximab+ bendamustine (CLL)
Arm Type
Experimental
Arm Description
Subjects will receive oral SAR245409 twice daily continuously and monthly bendamustine and rituximab intravenously
Intervention Type
Drug
Intervention Name(s)
SAR245409
Intervention Description
Pharmaceutical form:capsule Route of administration: oral
Primary Outcome Measure Information:
Title
Identification Of Dose-Limiting Toxicity (DLT) and Maximum Tolerated Dose (MTD)
Time Frame
4 weeks to 8 weeks
Secondary Outcome Measure Information:
Title
Number of subjects with treatment emergent adverse events
Time Frame
Time from receiving first dose of SAR245409 until 30 days after the last dose
Title
Pharmacokinetics (Cmax) of SAR245409
Time Frame
up to 2 months
Title
Pharmacokinetics (tmax) of SAR245409
Time Frame
up to 2 months
Title
Pharmacokinetics (AUC0-12h) of SAR245409
Time Frame
up to 2 months
Title
Pharmacokinetics (Ctrough) of SAR245409
Time Frame
up to 2 months
Title
Pharmacokinetics (AUC) of bendamustine
Time Frame
up to 2 months
Title
Pharmacokinetics (AUClast) of bendamustine
Time Frame
up to 2 months
Title
Pharmacokinetics (Ceoi) of bendamustine
Time Frame
up to 2 months
Title
Pharmacokinetics (tmax) of bendamustine
Time Frame
up to 2 months
Title
Pharmacokinetics (Cl) of bendamustine
Time Frame
up to 2 months
Title
Pharmacokinetics (Vss) of bendamustine
Time Frame
up to 2 months
Title
Pharmacokinetics (AUC0-7h) of rituximab
Time Frame
up to 2 months
Title
Pharmacokinetics (Ceoi) of rituximab
Time Frame
up to 2 months
Title
Pharmacokinetics (tmax) of rituximab
Time Frame
up to 2 months
Title
Efficacy as determined by objective response rate (ORR)
Time Frame
up to 4 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number 840004
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Investigational Site Number 840006
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Facility Name
Investigational Site Number 840002
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29406
Country
United States
12. IPD Sharing Statement
Learn more about this trial
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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