Study Combining SAR245409 With Bendamustine and/or Rituximab in Subjects With Indolent Lymphoma, Mantle Cell Lymphoma & Chronic Lymphocytic Leukemia
This study is currently recruiting participants.
Verified January 2013 by Sanofi
Sponsor:
Sanofi
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01410513
First received: July 26, 2011
Last updated: January 28, 2013
Last verified: January 2013
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Purpose
Primary Objective:
- To determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) for SAR245409 when administered in combination with bendamustine and/or 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 bendamustine and/or 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: | December 2014 |
| Estimated Primary Completion Date: | December 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 and either bendamustine or rituximab as doublet therapy, or with bendamustine and rituximab as triplet therapy, will be administered over a 28 day cycle.
Subjects receiving the doublet containing rituximab will receive rituximab for 4 - 8 weeks.
Subjects with iNHL or MCL receiving bendamustine as a triplet therapy will receive a maximum of 8 cycles of therapy. Subjects CLL receiving bendamustine as a triplet therapy will receive a maximum of 6 cycles of therapy.
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. pamtoprazole) 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
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-aventis.com |
Locations
| United States, Colorado | |
| Investigational Site Number 840004 | Recruiting |
| Aurora, Colorado, United States, 80045 | |
| United States, Georgia | |
| Investigational Site Number 840006 | Recruiting |
| Augusta, Georgia, United States, 30912 | |
| United States, New Jersey | |
| Investigational Site Number 840001 | Recruiting |
| New Brunswick, New Jersey, United States, 08903 | |
| United States, South Carolina | |
| Investigational Site Number 840002 | Recruiting |
| 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: | January 28, 2013 |
| 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 May 19, 2013