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Trial record 1 of 1 for:    NCT02663518
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A Trial of TTI-621 for Patients With Hematologic Malignancies and Selected Solid Tumors

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ClinicalTrials.gov Identifier: NCT02663518
Recruitment Status : Recruiting
First Posted : January 26, 2016
Last Update Posted : May 15, 2020
Sponsor:
Information provided by (Responsible Party):
Trillium Therapeutics Inc.

Tracking Information
First Submitted Date  ICMJE January 19, 2016
First Posted Date  ICMJE January 26, 2016
Last Update Posted Date May 15, 2020
Actual Study Start Date  ICMJE January 2016
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 10, 2019)
Incidence and severity of adverse events [ Time Frame: 42 months ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 25, 2016)
Dose-limiting Toxicity (DLT) [ Time Frame: 18 months ]
Number of participants with a DLT
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Trial of TTI-621 for Patients With Hematologic Malignancies and Selected Solid Tumors
Official Title  ICMJE 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
Brief Summary 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Masking Description:
Open label
Primary Purpose: Treatment
Condition  ICMJE
  • Hematologic Malignancies
  • Solid Tumor
Intervention  ICMJE
  • Drug: TTI-621
    Monotherapy
    Other Name: SIRPαFc
  • Drug: TTI-621 plus Rituximab
    Combination therapy
    Other Name: TTI-621 plus Rituxan
  • Drug: TTI-621 plus Nivolumab
    Combination therapy
    Other Name: TTI-621 plus Opdivo
Study Arms  ICMJE
  • Experimental: TTI-621 Escalation Phase
    The Escalation Phase will include multiple doses of TTI-621
    Intervention: Drug: TTI-621
  • Experimental: Indolent B-Cell Lymphoma
    Monotherapy expansion cohort with TTI-621
    Intervention: Drug: TTI-621
  • Experimental: Aggressive B-Cell Lymphoma
    Monotherapy expansion cohort with TTI-621
    Intervention: Drug: TTI-621
  • Experimental: T-Cell Lymphoma
    Monotherapy expansion cohort with TTI-621
    Intervention: Drug: TTI-621
  • Experimental: Hodgkin Lymphoma
    Monotherapy expansion cohort with TTI-621
    Intervention: Drug: TTI-621
  • Experimental: Chronic Lymphocytic Leukemia
    Monotherapy expansion cohort with TTI-621
    Intervention: Drug: TTI-621
  • Experimental: Acute Lymphoblastic Leukemia
    Monotherapy expansion cohort with TTI-621
    Intervention: Drug: TTI-621
  • Experimental: Multiple Myeloma
    Monotherapy expansion cohort with TTI-621
    Intervention: Drug: TTI-621
  • Experimental: Acute Myeloid Leukemia
    Monotherapy expansion cohort with TTI-621
    Intervention: Drug: TTI-621
  • Experimental: Myelodysplastic Syndrome
    Monotherapy expansion cohort with TTI-621
    Intervention: Drug: TTI-621
  • Experimental: Myeloproliferative Neoplasms
    Monotherapy expansion cohort with TTI-621
    Intervention: Drug: TTI-621
  • Experimental: Small Cell Lung Cancer
    Monotherapy expansion cohort with TTI-621
    Intervention: Drug: TTI-621
  • Experimental: Rituximab Combination
    Combination therapy expansion cohort with TTI-621 plus Rituximab for CD20 positive malignancies
    Intervention: Drug: TTI-621 plus Rituximab
  • Experimental: Nivolumab Combination
    Combination therapy expansion cohort with TTI-621 plus Nivolumab for Hodgkin Lymphoma
    Intervention: Drug: TTI-621 plus Nivolumab
  • Experimental: Cutaneous T-Cell Lymphoma (CTCL)
    Monotherapy expansion cohort with TTI-621
    Intervention: Drug: TTI-621
  • Experimental: Peripheral T-Cell Lymphoma (PTCL)
    Monotherapy expansion cohort with TTI-621
    Intervention: Drug: TTI-621
  • Experimental: Part 4: Cutaneous T-Cell Lymphoma (CTCL)
    Monotherapy expansion Part 4 (Dose Optimization) cohort with TTI-621
    Intervention: Drug: TTI-621
Publications * Johnson LDS, Banerjee S, Kruglov O, Viller NN, Horwitz SM, Lesokhin A, Zain J, Querfeld C, Chen R, Okada C, Sawas A, O'Connor OA, Sievers EL, Shou Y, Uger RA, Wong M, Akilov OE. Targeting CD47 in Sézary syndrome with SIRPαFc. Blood Adv. 2019 Apr 9;3(7):1145-1153. doi: 10.1182/bloodadvances.2018030577.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 8, 2018)
260
Original Estimated Enrollment  ICMJE
 (submitted: January 25, 2016)
156
Estimated Study Completion Date  ICMJE June 2021
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Kathleen Roberge, NP-C, MSN, MSc 857-412-7029 ext 211 kathleen@trilliumtherapeutics.com
Contact: Yaping Shou, MD, PhD yaping@trilliumtherapeutics.com
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02663518
Other Study ID Numbers  ICMJE TTI-621-01
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Trillium Therapeutics Inc.
Study Sponsor  ICMJE Trillium Therapeutics Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Trillium Therapeutics Inc.
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP