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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.

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

Condition or disease Intervention/treatment Phase
Hematologic Malignancies Solid Tumor Drug: TTI-621 Drug: TTI-621 plus Rituximab Drug: TTI-621 plus Nivolumab Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 260 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Masking Description: Open label
Primary Purpose: Treatment
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
Actual Study Start Date : January 2016
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : June 2021


Arm Intervention/treatment
Experimental: TTI-621 Escalation Phase
The Escalation Phase will include multiple doses of TTI-621
Drug: TTI-621
Monotherapy
Other Name: SIRPαFc

Experimental: Indolent B-Cell Lymphoma
Monotherapy expansion cohort with TTI-621
Drug: TTI-621
Monotherapy
Other Name: SIRPαFc

Experimental: Aggressive B-Cell Lymphoma
Monotherapy expansion cohort with TTI-621
Drug: TTI-621
Monotherapy
Other Name: SIRPαFc

Experimental: T-Cell Lymphoma
Monotherapy expansion cohort with TTI-621
Drug: TTI-621
Monotherapy
Other Name: SIRPαFc

Experimental: Hodgkin Lymphoma
Monotherapy expansion cohort with TTI-621
Drug: TTI-621
Monotherapy
Other Name: SIRPαFc

Experimental: Chronic Lymphocytic Leukemia
Monotherapy expansion cohort with TTI-621
Drug: TTI-621
Monotherapy
Other Name: SIRPαFc

Experimental: Acute Lymphoblastic Leukemia
Monotherapy expansion cohort with TTI-621
Drug: TTI-621
Monotherapy
Other Name: SIRPαFc

Experimental: Multiple Myeloma
Monotherapy expansion cohort with TTI-621
Drug: TTI-621
Monotherapy
Other Name: SIRPαFc

Experimental: Acute Myeloid Leukemia
Monotherapy expansion cohort with TTI-621
Drug: TTI-621
Monotherapy
Other Name: SIRPαFc

Experimental: Myelodysplastic Syndrome
Monotherapy expansion cohort with TTI-621
Drug: TTI-621
Monotherapy
Other Name: SIRPαFc

Experimental: Myeloproliferative Neoplasms
Monotherapy expansion cohort with TTI-621
Drug: TTI-621
Monotherapy
Other Name: SIRPαFc

Experimental: Small Cell Lung Cancer
Monotherapy expansion cohort with TTI-621
Drug: TTI-621
Monotherapy
Other Name: SIRPαFc

Experimental: Rituximab Combination
Combination therapy expansion cohort with TTI-621 plus Rituximab for CD20 positive malignancies
Drug: TTI-621 plus Rituximab
Combination therapy
Other Name: TTI-621 plus Rituxan

Experimental: Nivolumab Combination
Combination therapy expansion cohort with TTI-621 plus Nivolumab for Hodgkin Lymphoma
Drug: TTI-621 plus Nivolumab
Combination therapy
Other Name: TTI-621 plus Opdivo

Experimental: Cutaneous T-Cell Lymphoma (CTCL)
Monotherapy expansion cohort with TTI-621
Drug: TTI-621
Monotherapy
Other Name: SIRPαFc

Experimental: Peripheral T-Cell Lymphoma (PTCL)
Monotherapy expansion cohort with TTI-621
Drug: TTI-621
Monotherapy
Other Name: SIRPαFc

Experimental: Part 4: Cutaneous T-Cell Lymphoma (CTCL)
Monotherapy expansion Part 4 (Dose Optimization) cohort with TTI-621
Drug: TTI-621
Monotherapy
Other Name: SIRPαFc




Primary Outcome Measures :
  1. 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.




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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02663518


Contacts
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Contact: Kathleen Roberge, NP-C, MSN, MSc 857-412-7029 ext 211 kathleen@trilliumtherapeutics.com
Contact: Yaping Shou, MD, PhD yaping@trilliumtherapeutics.com

Locations
Show Show 18 study locations
Sponsors and Collaborators
Trillium Therapeutics Inc.
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Trillium Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT02663518    
Other Study ID Numbers: TTI-621-01
First Posted: January 26, 2016    Key Record Dates
Last Update Posted: May 15, 2020
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Trillium Therapeutics Inc.:
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
Additional relevant MeSH terms:
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Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Hematologic Diseases
Rituximab
Nivolumab
Immunoglobulin G
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents