Safety and Efficacy Study of a Dual PI3K Delta/Gamma Inhibitor in Hematological Malignancies (PI3K)

A Phase I, Dose Escalation Study to Evaluate Safety and Efficacy of RP6530, a Dual PI3K Delta/Gamma Inhibitor, in Patients With Relapsed or Refractory Hematologic Malignancies

The objective of this study is to evaluate the safety and efficacy of RP6530, a dual PI3K delta/gamma inhibitor in patients with hematologic malignancies.

Study Overview

• Status: Completed
• Conditions: Lymphoma, B-Cell; T-Cell Lymphoma
• Intervention / Treatment: Drug: RP6530

Detailed Description

The Maximum tolerated dose (MTD) will be determined based on the safety, pharmacokinetic (PK) and efficacy data. Safety analyses include AE's, AE's related to the drug, SAE's, laboratory values, vitals/ ECG and dose limiting toxicity (DLT). PK include measurement of peak plasma concentration (Cmax), area under the plasma concentration versus the time curve (AUC), time of maximum concentration observed (Tmax). Efficacy analyses include overall response rate (ORR) and duration of response (DOR).

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Paris, France
    • Rhizen Trial Site
• Italy
  • Milano, Italy
    • Rhizen Trial Site 1
  • Milano, Italy
    • Rhizen Trial Site 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Refractory to or relapsed after at least 1 prior treatment line.
• ECOG performance status ≤2
• Patients must be ≥18 years of age
• Able to give a written informed consent.

Exclusion Criteria:

• Any cancer therapy in the last 4 weeks or limited palliative radiation <2 weeks
• Patients with HBV, HCV or HIV infection
• Autologous hematologic stem cell transplant within 3 months of study entry. Allogeneic hematologic stem cell transplant within 12 months.
• Previous therapy with GS-1101 (CAL-101, idelalisib), IPI-145, TGR-1202 or any drug that specifically inhibits PI3K/ mTOR (including temsirolimus, everolimus), AKT or BTK Inhibitor (including Ibrutinib).
• Patients on immunosuppressive therapy including systemic corticosteroids.
• Patients who are receiving chronic systemic anticoagulation therapy (warfarin sodium or heparin, etc.).
• Patients with known history of liver disorders.
• Patients with uncontrolled Diabetes Type I or Type II
• Any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study.
• Women who are pregnant or lactating.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single arm; RP6530 administered orally	Drug: RP6530; Escalating doses starting at 25 mg BID; Other Names: PI3k Delta/ Gamma inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose (MTD) and pharmacokinetics (PK) of RP6530	To access maximum tolerated dose by clinical laboratory assessments, adverse events and dose limiting toxicities.; PK parameter AUC, Cmax, tmax, t1/2 will be determined.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical response following administration of RP6530	Overall response rate (ORR) and duration of response (DOR).	8 weeks

Collaborators and Investigators

• Sponsor: Rhizen Pharmaceuticals SA
• Investigators: Study Chair: Andrés JM Ferreri, MD, Ospedale San Raffaele S.r.l.; Principal Investigator: Carmelo Carlo-stella, MD, Humanitas Clinical and Research Centre; Principal Investigator: Richard Delarue, MD, Hôpital Necker-Enfants Malades

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: November 26, 2013
• First Submitted That Met QC Criteria: December 16, 2013
• First Posted (Estimate): December 23, 2013

Study Record Updates

• Last Update Posted (Estimate): June 24, 2016
• Last Update Submitted That Met QC Criteria: June 23, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: CLL, SLL, NHL, SLL, PTCL, CTCL, MM, AML
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Phosphoinositide-3 Kinase Inhibitors; Tenalisib
• Other Study ID Numbers: RP6530-1301; 2013-003769-32 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO