Clinical Trials /

Carfilzomib and TGR-1202 in Treatment of R/R Lymphoma

NCT02867618

Description:

This is an open label, phase I/II, dose-escalation study in the initial phase I followed by a phase II. The primary objective of the phase I is to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of the combinations of TGR-1202 and carfilzomib in participants with relapsed and refractory (R/R) non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL). The safety and toxicity of this combination will be evaluated throughout the entire study. If the combination of TGR-1202 and carfilzomib is found to be feasible and an MTD is established, the phase II part of the study will be initiated. Phase II will consist of a 2-stage design of the combination of TGR-1202 and carfilzomib for participants with R/R NHL.

Related Conditions:
  • Chronic Lymphocytic Leukemia
  • Diffuse Large B-Cell Lymphoma
  • Hodgkin Lymphoma
  • Non-Hodgkin Lymphoma
  • Small Lymphocytic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Carfilzomib and TGR-1202 in Treatment of R/R Lymphoma
  • Official Title: Phase I/II Study of Carfilzomib and a PI3Kdelta Inhibitor TGR-1202 in the Treatment of Patients With Relapsed or Refractory Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: AAAP5661
  • NCT ID: NCT02867618

Conditions

  • Hodgkin Disease
  • Lymphoma, Non-hodgkin

Interventions

DrugSynonymsArms
CarfilzomibKyprolisCarfilzomib + TGR-1202
TGR-1202Carfilzomib + TGR-1202

Purpose

This is an open label, phase I/II, dose-escalation study in the initial phase I followed by a phase II. The primary objective of the phase I is to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of the combinations of TGR-1202 and carfilzomib in participants with relapsed and refractory (R/R) non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL). The safety and toxicity of this combination will be evaluated throughout the entire study. If the combination of TGR-1202 and carfilzomib is found to be feasible and an MTD is established, the phase II part of the study will be initiated. Phase II will consist of a 2-stage design of the combination of TGR-1202 and carfilzomib for participants with R/R NHL.

Detailed Description

      Dysregulated c-Myc is associated with resistance to chemotherapy and poor survival in
      aggressive lymphomas. Novel strategies that target this biology could markedly improve the
      outcome of these participants. To date no drugs that directly target Myc have been approved
      for cancer treatment. Recent results by Deng et al. (Blood. 2017 Jan 5. PMID: 27784673)
      described a highly synergistic regimen discovered in preclinical models, through combining
      TGR-1202, an investigational drug that inhibits PI3K delta, and carfilzomib, a drug approved
      by the FDA for multiple myeloma. Importantly, the combination of TGR-1202 and carfilzomib
      acts by potently silencing the translation of c-Myc and inducing apoptosis in many cell
      lines and primary lymphoma cells representing broad histological subtypes of lymphoma. These
      results suggest that TGR-1202 and carfilzomib may be highly effective in relapsed and
      refractory lymphoma where c-Myc plays a key pathological role.
    

Trial Arms

NameTypeDescriptionInterventions
Carfilzomib + TGR-1202ExperimentalOral TGR-1202 will be given PO once daily on Days 1-28 and carfilzomib given intravenously twice a week for 3 consecutive weeks, on days 1, 2, 8, 9, 15, and 16 on the 28-day cycle.
  • Carfilzomib
  • TGR-1202

Eligibility Criteria

        Inclusion Criteria:

        Phase I: Patients must have histologically confirmed R/R NHL or HL (defined by WHO
        criteria). Patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma
        (SLL) are eligible.

        Phase II: Patients must have histologically confirmed R/R NHL (as defined by WHO
        criteria).

          -  Must have received front - line chemotherapy. No upper limit for the number of prior
             therapies

          -  Evaluable Disease in the Phase I, and measurable disease as defined in Section 11 in
             the Phase II.

          -  Age >18 years.

          -  ECOG performance status <2

          -  Patients must have adequate organ and marrow function as defined in Section 3.

          -  Adequate Contraception

          -  Ability to understand and the willingness to sign a written informed consent
             document.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose
Time Frame:9 months
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Changchun Deng

Last Updated

February 16, 2017