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

Sponsor

Sanofi (Industry)

Overall Status

Completed

CT.gov ID

NCT01410513

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

12.3

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

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

Condition or Disease	Intervention/Treatment	Phase
Indolent Non-Hodgkin Lymphoma Mantle Cell Lymphoma Chronic Lymphocytic Leukemia	Drug: SAR245409	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

37 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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 Patients With Relapsed or Refractory Indolent B-cell Non-Hodgkin Lymphoma, Mantle Cell Lymphoma or Chronic Lymphocytic Leukemia

Study Start Date :

Dec 1, 2011

Actual Primary Completion Date :

May 1, 2014

Actual Study Completion Date :

May 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

Identification Of Dose-Limiting Toxicity (DLT) and Maximum Tolerated Dose (MTD) [4 weeks to 8 weeks]

Secondary Outcome Measures

Number of subjects with treatment emergent adverse events [Time from receiving first dose of SAR245409 until 30 days after the last dose]
Pharmacokinetics (Cmax) of SAR245409 [up to 2 months]
Pharmacokinetics (tmax) of SAR245409 [up to 2 months]
Pharmacokinetics (AUC0-12h) of SAR245409 [up to 2 months]
Pharmacokinetics (Ctrough) of SAR245409 [up to 2 months]
Pharmacokinetics (AUC) of bendamustine [up to 2 months]
Pharmacokinetics (AUClast) of bendamustine [up to 2 months]
Pharmacokinetics (Ceoi) of bendamustine [up to 2 months]
Pharmacokinetics (tmax) of bendamustine [up to 2 months]
Pharmacokinetics (Cl) of bendamustine [up to 2 months]
Pharmacokinetics (Vss) of bendamustine [up to 2 months]
Pharmacokinetics (AUC0-7h) of rituximab [up to 2 months]
Pharmacokinetics (Ceoi) of rituximab [up to 2 months]
Pharmacokinetics (tmax) of rituximab [up to 2 months]
Efficacy as determined by objective response rate (ORR) [up to 4 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site Number 840004	Aurora	Colorado	United States	80045
2	Investigational Site Number 840006	Augusta	Georgia	United States	30912
3	Investigational Site Number 840002	Charleston	South Carolina	United States	29406