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A Trial of TTI-622 in Patients With Advanced Hematologic Malignancies (TTI-622-01)

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ClinicalTrials.gov Identifier: NCT03530683
Recruitment Status : Recruiting
First Posted : May 21, 2018
Last Update Posted : July 15, 2021
Sponsor:
Information provided by (Responsible Party):
Trillium Therapeutics Inc.

Tracking Information
First Submitted Date  ICMJE May 8, 2018
First Posted Date  ICMJE May 21, 2018
Last Update Posted Date July 15, 2021
Actual Study Start Date  ICMJE May 1, 2018
Estimated Primary Completion Date April 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 9, 2021)
  • Phase 1a: Frequency and severity of adverse events (AEs) [ Time Frame: Through study completion, up to 18 months ]
    To characterize the safety profile (incidence of AEs) and dose-limiting toxicities (DLTs) of TTI-622.
  • Phase 1b: Frequency and severity of AEs [ Time Frame: Through study completion, up to 18 months ]
    To characterize the safety profile (incidence of AEs).
  • Phase 1b: Efficacy of each combination treatment [ Time Frame: Through study completion, up to 18 months ]
    To evaluate preliminary efficacy (response rate) of each combination treatment in the 3 Cohorts (A to C).
Original Primary Outcome Measures  ICMJE
 (submitted: May 8, 2018)
Frequency and severity of adverse events [ Time Frame: 36 ]
To characterize the safety profile and dose-limiting toxicities (DLTs) of TTI-622.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 9, 2021)
  • Phase 1a: Characterize the TTI-622 pharmacokinetics (PK) parameter t1/2 [ Time Frame: Through study completion, up to 18 months ]
    To characterize t1/2 of TTI-622.
  • Phase 1a: Characterize the TTI-622 PK parameter AUC0-t [ Time Frame: Through study completion, up to 18 months ]
    To characterize AUC0-t of TTI-622.
  • Phase 1a: Characterize the TTI-622 PK parameter AUC0-tau [ Time Frame: Through study completion, up to 18 months ]
    To characterize AUC0-tau of TTI-622.
  • Phase 1a: Characterize the TTI-622 PK parameter AUC0-infinity [ Time Frame: Through study completion, up to 18 months ]
    To characterize AUC0-infinity of TTI-622.
  • Phase 1a: Characterize the TTI-622 PK parameter Tmax [ Time Frame: Through study completion, up to 18 months ]
    To characterize Tmax of TTI-622.
  • Phase 1a: Characterize the TTI-622 PK parameter Cmax [ Time Frame: Through study completion, up to 18 months ]
    To characterize Cmax of TTI-622.
  • Phase 1a: Characterize the TTI-622 PK parameter Cmin [ Time Frame: Through study completion, up to 18 months ]
    To characterize Cmin of TTI-622.
  • Phase 1a: Characterize the TTI-622 PK parameter Cavg [ Time Frame: Through study completion, up to 18 months ]
    To characterize Cavg of TTI-622.
  • Phase 1a: Characterize the clearance of TTI-622 [ Time Frame: Through study completion, up to 18 months ]
    To characterize clearance of TTI-622.
  • Phase 1a: Characterize the volume of distribution of TTI-622 [ Time Frame: Through study completion, up to 18 months ]
    To characterize volume of distribution of TTI-622.
  • Phase 1a: Characterize the immunogenicity of TTI-622 [ Time Frame: Through study completion, up to 18 months ]
    To characterize the incidence of anti-drug antibodies (ADA).
  • Phase 1a: Characterize the preliminary evidence of antitumor activity of TTI-622: overall response rate [ Time Frame: Through study completion, up to 18 months ]
    To determine the overall response rate (ORR) for participants treated with TTI-622.
  • Phase 1a: Characterize the preliminary evidence of antitumor activity of TTI-622: disease control rate [ Time Frame: Through study completion, up to 18 months ]
    To determine the disease control rate (DCR) for participants treated with TTI-622.
  • Phase 1a: Characterize the preliminary evidence of antitumor activity of TTI-622: time to response [ Time Frame: Through study completion, up to 18 months ]
    To determine the time to response (TTR) for participants treated with TTI-622.
  • Phase 1a: Characterize the preliminary evidence of antitumor activity of TTI-622: duration of response [ Time Frame: Through study completion, up to 18 months ]
    To determine the duration of response (DOR) for participants treated with TTI-622.
  • Phase 1a: Characterize the preliminary evidence of antitumor activity of TTI-622: progression free survival [ Time Frame: Through study completion, up to 18 months ]
    To determine the progression free survival (PFS) time for participants treated with TTI-622.
  • Phase 1b: Characterize the TTI-622 PK parameter t1/2 when combined with selected anticancer treatments [ Time Frame: Through study completion, up to 18 months ]
    To characterize t1/2 of TTI-622 when combined with selected anticancer treatments.
  • Phase 1b: Characterize the TTI-622 PK parameter AUC0-t when combined with selected anticancer treatments [ Time Frame: Through study completion, up to 18 months ]
    To characterize AUC0-t of TTI-622 when combined with selected anticancer treatments.
  • Phase 1b: Characterize the TTI-622 PK parameter AUC0-tau when combined with selected anticancer treatments [ Time Frame: Through study completion, up to 18 months ]
    To characterize AUC0-tau of TTI-622 when combined with selected anticancer treatments.
  • Phase 1b: Characterize the TTI-622 PK parameter AUC0-infinity when combined with selected anticancer treatments [ Time Frame: Through study completion, up to 18 months ]
    To characterize AUC0-infinity of TTI-622 when combined with selected anticancer treatments.
  • Phase 1b: Characterize the TTI-622 PK parameter Tmax when combined with selected anticancer treatments [ Time Frame: Through study completion, up to 18 months ]
    To characterize Tmax of TTI-622 when combined with selected anticancer treatments.
  • Phase 1b: Characterize the TTI-622 PK parameter Cmax when combined with selected anticancer treatments [ Time Frame: Through study completion, up to 18 months ]
    To characterize Cmax of TTI-622 when combined with selected anticancer treatments.
  • Phase 1b: Characterize the TTI-622 PK parameter Cmin when combined with selected anticancer treatments [ Time Frame: Through study completion, up to 18 months ]
    To characterize Cmin of TTI-622 when combined with selected anticancer treatments.
  • Phase 1b: Characterize the TTI-622 PK parameter Cavg when combined with selected anticancer treatments [ Time Frame: Through study completion, up to 18 months ]
    To characterize Cavg of TTI-622 when combined with selected anticancer treatments.
  • Phase 1b: Characterize the clearance of TTI-622 when combined with selected anticancer treatments [ Time Frame: Through study completion, up to 18 months ]
    To characterize clearance of TTI-622 when combined with selected anticancer treatments.
  • Phase 1b: Characterize the volume of distribution of TTI-622 when combined with selected anticancer treatments [ Time Frame: Through study completion, up to 18 months ]
    To characterize volume of distribution of TTI-622 when combined with selected anticancer treatments.
  • Phase 1b: Characterize the immunogenicity of TTI-622 when combined with selected anticancer treatments [ Time Frame: Through study completion, up to 18 months ]
    To characterize the incidence of anti-drug antibodies (ADA).
  • Phase 1b: Characterize the preliminary evidence of antitumour activity of TTI-622 when combined with selected anticancer treatments: disease control rate [ Time Frame: Through study completion, up to 18 months ]
    To determine the disease control rate (DCR) for participants treated with TTI-622 when combined with selected anticancer treatments.
  • Phase 1b: Characterize the preliminary evidence of antitumour activity of TTI-622 when combined with selected anticancer treatments: time to response [ Time Frame: Through study completion, up to 18 months ]
    To determine the time to response (TTR) for participants treated with TTI-622 when combined with selected anticancer treatments.
  • Phase 1b: Characterize the preliminary evidence of antitumour activity of TTI-622 when combined with selected anticancer treatments: event-free survival [ Time Frame: Through study completion, up to 18 months ]
    To determine event-free survival (EFS; for Cohorts A and B) time for participants treated with TTI-622 when combined with selected anticancer treatments.
  • Phase 1b: Characterize the preliminary evidence of antitumour activity of TTI-622 when combined with selected anticancer treatments: duration of response [ Time Frame: Through study completion, up to 18 months ]
    To determine the duration of response (DOR) for participants treated with TTI-622 when combined with selected anticancer treatments.
  • Phase 1b: Characterize the preliminary evidence of antitumour activity of TTI-622 when combined with selected anticancer treatments: progression-free survival [ Time Frame: Through study completion, up to 18 months ]
    To determine the progression-free survival (PFS) time for participants treated with TTI-622 when combined with selected anticancer treatments.
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-622 in Patients With Advanced Hematologic Malignancies
Official Title  ICMJE A Phase 1a/1b Dose-Escalation and Expansion Trial of TTI-622 in Patients With Advanced Hematologic Malignancies, Including Lymphoma, Leukemia, and Multiple Myeloma
Brief Summary Multicenter, open-label, phase 1a/1b Dose Escalation and Expansion Trial of TTI-622 in subjects with Advanced Hematologic Malignancies, Including Lymphoma, Leukemia, and Multiple Myeloma.
Detailed Description

This is a trial of TTI-622 in subjects with relapsed or refractory lymphoma or multiple myeloma (MM) and subjects with newly diagnosed acute myeloid leukemia (AML).

This trial will be conducted in 2 phases: Phase 1a (Dose-Escalation Phase for Single-Agent TTI-622) and Phase 1b (TTI-622 Combinations).

In the Dose-Escalation Phase for Single-Agent TTI-622, subjects with relapsed or refractory lymphoma will be enrolled in sequential dose cohorts.

In the Combination Treatment part, subjects will be included in 1 of 3 cohorts: (1) subjects with newly diagnosed TP53-mutated AML will be treated with TTI-622 + azacitidine; (2) elderly subjects (≥75 years old) or subjects unfit for intensive induction chemotherapies with newly diagnosed TP53-wildtype AML will be treated with TTI-622 + azacitidine and venetoclax; and (3) subjects with relapsed or refractory MM will be treated with TTI-622 + carfilzomib and dexamethasone.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Lymphoma
  • Multiple Myeloma
  • Acute Myeloid Leukemia
Intervention  ICMJE
  • Drug: TTI-622
    TTI-622 will be administered by intravenous infusion.
    Other Name: SIRPα-IgG4 Fc
  • Drug: Azacitidine
    75 mg/m^2 intravenous (IV) or subcutaneous (SC) daily for 7 days, repeated every 4 weeks
    Other Name: VIDAZA
  • Drug: Venetoclax
    400 mg orally daily for each day of each cycle (except for Cycle 1, where Day 1=100 mg and Day 2=200 mg; first 7 doses taken in clinic). The ramp-up and target dose of venetoclax will be adjusted per the package insert in subjects who are taking concomitant moderate or strong CYP3A4 inhibitors or posaconazole
    Other Name: VENCLEXTA
  • Drug: Carfilzomib
    Days 1, 8, and 15 of 28-day cycles; 20 mg/m^2 IV given on Cycle (C) 1 Day (D) 1, and if tolerated, then 70 mg/m^2 IV given starting on C1D8 and subsequent doses thereafter
    Other Name: KYPROLIS
  • Drug: Dexamethasone
    40 mg orally or IV on Days 1, 8, 15, and 22 of 28-day cycles
Study Arms  ICMJE
  • Experimental: TTI-622 Monotherapy
    Intervention: Drug: TTI-622
  • Experimental: Cohort A: TTI-622 + Azacitidine
    Interventions:
    • Drug: TTI-622
    • Drug: Azacitidine
  • Experimental: Cohort B: TTI-622 + Azacitidine and Venetoclax
    Interventions:
    • Drug: TTI-622
    • Drug: Azacitidine
    • Drug: Venetoclax
  • Experimental: Cohort C: TTI-622 + Carfilzomib and Dexamethasone
    Interventions:
    • Drug: TTI-622
    • Drug: Carfilzomib
    • Drug: Dexamethasone
Publications * Not Provided

*   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: July 9, 2021)
150
Original Estimated Enrollment  ICMJE
 (submitted: May 8, 2018)
156
Estimated Study Completion Date  ICMJE December 30, 2022
Estimated Primary Completion Date April 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria (Phase 1a and Phase 1b, all Cohorts):

  1. Available fresh or archived tumor tissue.
  2. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
  3. Adequate coagulation function.
  4. Adequate hepatic function.
  5. Adequate hematologic status.
  6. Adequate renal function.
  7. Recovery from non-hematopoietic toxicities of previous anticancer drugs or radiotherapy or previous surgeries to ≤Grade 1 (or to baseline grade if condition was pre-existing).

Key Inclusion Criteria (Phase 1a): Histologically confirmed relapsed/refractory lymphoma (Hodgkin or non-Hodgkin).

Key Inclusion Criteria (Phase 1b Cohort A): Histologically confirmed, newly diagnosed TP53-mutated Acute Myeloid Leukemia (AML).

Key Inclusion Criteria (Phase 1b Cohort B): Histologically confirmed, newly diagnosed TP53-wildtype AML, elderly or unfit for more aggressive treatment.

Inclusion Criteria (Phase 1b Cohort C): Histologically documented relapsed/refractory Multiple Myeloma (MM).

Key Exclusion Criteria (Phase 1a and Phase 1b, all Cohorts):

  1. Known, current central nervous system disease involvement.
  2. Use of any investigational agent or any anticancer drug within 14 days before planned start of study treatment (within 4 weeks for antibody-based therapies and within 8 weeks for cell-based therapies).
  3. Subjects who have undergone radiation therapy within 14 days of study treatment administration.
  4. Hematopoietic stem cell transplant within 90 days before the planned start of study treatment or subjects with active graft-vs-host disease, with the exception of Grade 1 skin involvement.
  5. Major surgery within 30 days before planned start of study treatment.
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 Large, RN, MSN 875-412-7029 ext 211 kathleen2@trilliumtherapeutics.com
Contact: Amirah Shahin amirah@trilliumtherapeutics.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03530683
Other Study ID Numbers  ICMJE TTI-622-01
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Trillium Therapeutics Inc.
Study Sponsor  ICMJE Trillium Therapeutics Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Ingmar Bruns, MD, PhD Trillium Therapeutics Inc.
PRS Account Trillium Therapeutics Inc.
Verification Date July 2021

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