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

Chronic Lymphocytic Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01410513
• Other study ID #: TCD12012
• Secondary ID: U1111-1119-2906
• Status: Completed
• Phase: Phase 1
• First received: July 26, 2011
• Last updated: March 31, 2016
• Start date: December 2011
• Est. completion date: May 2014

Study information

• Verified date: September 2014
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: May 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Indolent Non-Hodgkin Lymphoma
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, Mantle-Cell
• Lymphoma, Non-Hodgkin
• Mantle Cell Lymphoma

Intervention

Drug:
• SAR245409
Pharmaceutical form:capsule Route of administration: oral

Locations

Country	Name	City	State
United States	Investigational Site Number 840006	Augusta	Georgia
United States	Investigational Site Number 840004	Aurora	Colorado
United States	Investigational Site Number 840002	Charleston	South Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Identification Of Dose-Limiting Toxicity (DLT) and Maximum Tolerated Dose (MTD)		4 weeks to 8 weeks	Yes
Secondary	Number of subjects with treatment emergent adverse events		Time from receiving first dose of SAR245409 until 30 days after the last dose	No
Secondary	Pharmacokinetics (Cmax) of SAR245409		up to 2 months	No
Secondary	Pharmacokinetics (tmax) of SAR245409		up to 2 months	No
Secondary	Pharmacokinetics (AUC0-12h) of SAR245409		up to 2 months	No
Secondary	Pharmacokinetics (Ctrough) of SAR245409		up to 2 months	No
Secondary	Pharmacokinetics (AUC) of bendamustine		up to 2 months	No
Secondary	Pharmacokinetics (AUClast) of bendamustine		up to 2 months	No
Secondary	Pharmacokinetics (Ceoi) of bendamustine		up to 2 months	No
Secondary	Pharmacokinetics (tmax) of bendamustine		up to 2 months	No
Secondary	Pharmacokinetics (Cl) of bendamustine		up to 2 months	No
Secondary	Pharmacokinetics (Vss) of bendamustine		up to 2 months	No
Secondary	Pharmacokinetics (AUC0-7h) of rituximab		up to 2 months	No
Secondary	Pharmacokinetics (Ceoi) of rituximab		up to 2 months	No
Secondary	Pharmacokinetics (tmax) of rituximab		up to 2 months	No
Secondary	Efficacy as determined by objective response rate (ORR)		up to 4 years	No