Clinical Trials /

A Trial of TTI-621 for Patients With Hematologic Malignancies and Selected Solid Tumors

NCT02663518

Description:

Multicenter, open-label, phase 1a/1b trial of TTI-621 in subjects with relapsed or refractory hematologic malignancies and selected solid tumors.

Related Conditions:
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Chronic Lymphocytic Leukemia
  • Hematopoietic and Lymphoid Malignancy
  • Hodgkin Lymphoma
  • Lymphoma
  • Malignant Solid Tumor
  • Multiple Myeloma
  • Myelodysplastic Syndromes
  • Myeloproliferative Neoplasm
  • Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Trial of TTI-621 for Patients With Hematologic Malignancies and Selected Solid Tumors
  • Official Title: A Phase 1a/1b Dose Escalation and Expansion Trial of TTI-621, a Novel Biologic Targeting CD47, in Subjects With Relapsed or Refractory Hematologic Malignancies and Selected Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: TTI-621-01
  • NCT ID: NCT02663518

Conditions

  • Hematologic Malignancies
  • Solid Tumor

Interventions

DrugSynonymsArms
TTI-621SIRPαFcTTI-621 Escalation Phase
TTI-621 plus RituximabTTI-621 plus RituxanRituximab Combination
TTI-621 plus NivolumabTTI-621 plus OpdivoNivolumab Combination

Purpose

Multicenter, open-label, phase 1a/1b trial of TTI-621 in subjects with relapsed or refractory hematologic malignancies and selected solid tumors.

Detailed Description

      This is a trial of TTI-621 in subjects with relapsed or refractory hematologic malignancies
      and selected solid tumors.

      TTI-621 (SIRPαFc) is a soluble recombinant fusion protein created by directly linking the
      sequences encoding the N-terminal CD47 binding domain of human SIRPα with the Fc domain of
      human immunoglobulin (IgG1). TTI-621 acts by binding human CD47 and preventing it from
      delivering an inhibitory "do not eat" (anti phagocytic) signal to macrophages.

      This trial will be conducted in 2 phases and 4 parts: Phase 1a Part 1 (escalation phase) and
      Phase 1b Parts 2-4 (expansion phase).

      In the dose Escalation Phase (phase 1a Part 1), subjects with lymphoma will be enrolled in
      sequential dose cohorts to receive TTI-621 to characterize safety, tolerability,
      pharmacokinetics, and the maximum-tolerated dose (MTD).

      In the Expansion Phase (phase 1b Parts 2-4), TTI-621 will be given to subjects with a variety
      of hematologic malignancies and selected solid tumors to further define safety and to
      characterize efficacy. In the Expansion Phase Part 2, the safety and efficacy of TTI-621 will
      also be assessed when it is given in combination with other anti-cancer drugs. The dose of
      TTI-621 to be delivered in the Expansion Phase Parts 2-3 of the study may be increased or
      decreased based on the subject's tolerability and on the subject's response to treatment.

      In the phase 1b dose optimization of the study (Part 4), further dose escalation of TTI-621,
      beyond the dose determined during phase 1a dose escalation, will be pursued in patients with
      relapsed and/or refractory CTCL following a 3+3 escalation design and using a revised DLT
      criteria to further evaluate the safety and tolerability of TTI-621 at dose levels higher
      than the initially recommended phase 1b Parts 2-3.

      Secondary objectives include further characterization of the pharmacokinetics,
      pharmacodynamics, and development of ADA; and to gain preliminary evidence of the anti-tumor
      activity of TTI-621 in subjects with a variety of hematologic malignancies and selected solid
      tumors. In addition, the safety of TTI-621 will be evaluated in combination with other
      anti-cancer agents.
    

Trial Arms

NameTypeDescriptionInterventions
TTI-621 Escalation PhaseExperimentalThe Escalation Phase will include multiple doses of TTI-621
  • TTI-621
Indolent B-Cell LymphomaExperimentalMonotherapy expansion cohort with TTI-621
  • TTI-621
Aggressive B-Cell LymphomaExperimentalMonotherapy expansion cohort with TTI-621
  • TTI-621
T-Cell LymphomaExperimentalMonotherapy expansion cohort with TTI-621
  • TTI-621
Hodgkin LymphomaExperimentalMonotherapy expansion cohort with TTI-621
  • TTI-621
Chronic Lymphocytic LeukemiaExperimentalMonotherapy expansion cohort with TTI-621
  • TTI-621
Acute Lymphoblastic LeukemiaExperimentalMonotherapy expansion cohort with TTI-621
  • TTI-621
Multiple MyelomaExperimentalMonotherapy expansion cohort with TTI-621
  • TTI-621
Acute Myeloid LeukemiaExperimentalMonotherapy expansion cohort with TTI-621
  • TTI-621
Myelodysplastic SyndromeExperimentalMonotherapy expansion cohort with TTI-621
  • TTI-621
Myeloproliferative NeoplasmsExperimentalMonotherapy expansion cohort with TTI-621
  • TTI-621
Small Cell Lung CancerExperimentalMonotherapy expansion cohort with TTI-621
  • TTI-621
Rituximab CombinationExperimentalCombination therapy expansion cohort with TTI-621 plus Rituximab for CD20 positive malignancies
  • TTI-621 plus Rituximab
Nivolumab CombinationExperimentalCombination therapy expansion cohort with TTI-621 plus Nivolumab for Hodgkin Lymphoma
  • TTI-621 plus Nivolumab
Cutaneous T-Cell Lymphoma (CTCL)ExperimentalMonotherapy expansion cohort with TTI-621
  • TTI-621
Peripheral T-Cell Lymphoma (PTCL)ExperimentalMonotherapy expansion cohort with TTI-621
  • TTI-621
Part 4: Cutaneous T-Cell Lymphoma (CTCL)ExperimentalMonotherapy expansion Part 4 (Dose Optimization) cohort with TTI-621
  • TTI-621

Eligibility Criteria

        Inclusion Criteria:

          1. Advanced measurable malignancy

          2. Adequate hematologic status

          3. Relapsed or are refractory following at least 2 prior systemic therapeutic attempts (1
             prior systemic attempt for PTCL). For CTCL, extracorporal photochemotherapy (ECP) will
             be considered a systemic therapy. Local radiation and topical agents are not systemic
             therapies.

          4. Adequate coagulation function

          5. Adequate hepatic function

          6. Adequate renal function

        Exclusion Criteria:

          1. Known, current central nervous system disease involvement or untreated brain
             metastases

          2. Allogeneic transplant within 30 days prior to the planned start of treatment or
             subjects with active graft-vs-host disease with the exception of Grade 1 skin
             involvement

          3. History of hemolytic anemia or bleeding diathesis
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence and severity of adverse events
Time Frame:42 months
Safety Issue:
Description:Safety and tolerability of TTI-621 when given alone and in combination with other anti-cancer agents to subjects with a variety of hematologic malignancies and with selected solid tumors, and to evaluate the safety of a standardized intra-subject TTI-621 dose intensification schedule. Part 4: To further evaluate the safety and tolerability of TTI-621 at dose levels higher than the initially recommended phase 1b Parts 2 and 3 dose and to reassess the MTD and/or recommended phase 2 dose per revised DLT criteria following a 3+3 dose escalation schema.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Trillium Therapeutics Inc.

Trial Keywords

  • T-Cell
  • CTCL
  • PTCL
  • ALL
  • Rituximab
  • Nivolumab
  • TTI-621
  • Solid Tumor
  • Hematologic Malignancies
  • Lymphoma
  • Cutaneous T-Cell Lymphoma
  • Peripheral T-Cell Lymphoma
  • Acute Lymphoblastic Leukemia
  • CD47

Last Updated

September 9, 2019