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

Sponsor
Trillium Therapeutics Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03530683
Collaborator
(none)
350
Enrollment
14
Locations
6
Arms
74
Anticipated Duration (Months)
25
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

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 and Single-Agent).

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 and Single-Agent Treatment part, subjects will be included in 1 of 9 cohorts: (Cohort A) subjects with newly diagnosed TP53-mutated AML will be treated with TTI-622 + azacitidine; (Cohort B) 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; (Cohort C1, C2, and C3) subjects with relapsed or refractory MM will be treated with TTI-622 + carfilzomib and dexamethasone; (Cohort D1 and D2) subjects in relapsed or refractory CD20+ diffuse large B-cell lymphoma will be treated with TTI-622 + an anti-CD20 targeting agent; and (Cohort E1 and E2) subjects with relapsed refractory MM will be treated with single-agent TTI-622.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
350 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Intervention Model Description:
Parallel AssignmentParallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1a/1b Dose-Escalation and Expansion Trial of TTI-622 in Patients With Advanced Hematologic Malignancies, Including Lymphoma, Leukemia, and Multiple Myeloma
Actual Study Start Date :
May 1, 2018
Anticipated Primary Completion Date :
Jun 30, 2023
Anticipated Study Completion Date :
Jun 30, 2024

Arms and Interventions

ArmIntervention/Treatment
Experimental: TTI-622 Monotherapy

Drug: TTI-622
TTI-622 will be administered by intravenous infusion.
Other Names:
  • SIRPα-IgG4 Fc
  • Experimental: Cohort A: TTI-622 + Azacitidine

    Drug: TTI-622
    TTI-622 will be administered by intravenous infusion.
    Other Names:
  • SIRPα-IgG4 Fc
  • Drug: Azacitidine
    75 mg/m^2 intravenous (IV) or subcutaneous (SC) daily for 7 days, repeated every 4 weeks
    Other Names:
  • VIDAZA
  • Experimental: Cohort B: TTI-622 + Azacitidine and Venetoclax

    Drug: TTI-622
    TTI-622 will be administered by intravenous infusion.
    Other Names:
  • SIRPα-IgG4 Fc
  • Drug: Azacitidine
    75 mg/m^2 intravenous (IV) or subcutaneous (SC) daily for 7 days, repeated every 4 weeks
    Other Names:
  • 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 Names:
  • VENCLEXTA
  • Experimental: Cohort C1, C2 and C3: TTI-622 (low, intermediate and high dose) + Carfilzomib and Dexamethasone

    Drug: TTI-622
    TTI-622 will be administered by intravenous infusion.
    Other Names:
  • SIRPα-IgG4 Fc
  • 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 Names:
  • KYPROLIS
  • Drug: Dexamethasone
    40 mg orally or IV on Days 1, 8, 15, and 22 of 28-day cycles

    Experimental: Cohort D1 and D2: TTI-622 (low and high dose) + an anti-CD20 targeting agent

    Drug: TTI-622
    TTI-622 will be administered by intravenous infusion.
    Other Names:
  • SIRPα-IgG4 Fc
  • Drug: anti-CD20 Targeting agent
    375 mg/m^2 weekly for up to eight doses
    Other Names:
  • Ruxience or Rituxan
  • Experimental: Cohort E1 and E2: single-agent TTI-622 (low and high dose)

    Drug: TTI-622
    TTI-622 will be administered by intravenous infusion.
    Other Names:
  • SIRPα-IgG4 Fc
  • Outcome Measures

    Primary Outcome Measures

    1. Phase 1a: Frequency and severity of adverse events (AEs) [Through study completion, up to 18 months]

      To characterize the safety profile (incidence of AEs) and dose-limiting toxicities (DLTs) of TTI-622.

    2. Phase 1b: Frequency and severity of AEs [Through study completion, up to 30 months]

      To characterize the safety profile (incidence of AEs).

    3. Phase 1b: Efficacy of each combination treatment [Through study completion, up to 30 months]

      To evaluate preliminary efficacy (response rate) of each combination treatment in the 7 combination cohorts (A, B, C1, C2, C3, D1, to D2) and for single agent treatment (Cohort E1 and E2).

    4. Phase 1b: Recommended dose of TTI-622 [Through study completion, up to 30 months]

      To determine the recommended dose of TTI-622 as a single agent.

    Secondary Outcome Measures

    1. Phase 1a: Characterize the TTI-622 pharmacokinetics (PK) parameter t1/2 [Through study completion, up to 18 months]

      To characterize t1/2 of TTI-622.

    2. Phase 1a: Characterize the TTI-622 PK parameter AUC0-t [Through study completion, up to 18 months]

      To characterize AUC0-t of TTI-622.

    3. Phase 1a: Characterize the TTI-622 PK parameter AUC0-tau [Through study completion, up to 18 months]

      To characterize AUC0-tau of TTI-622.

    4. Phase 1a: Characterize the TTI-622 PK parameter AUC0-infinity [Through study completion, up to 18 months]

      To characterize AUC0-infinity of TTI-622.

    5. Phase 1a: Characterize the TTI-622 PK parameter Tmax [Through study completion, up to 18 months]

      To characterize Tmax of TTI-622.

    6. Phase 1a: Characterize the TTI-622 PK parameter Cmax [Through study completion, up to 18 months]

      To characterize Cmax of TTI-622.

    7. Phase 1a: Characterize the TTI-622 PK parameter Cmin [Through study completion, up to 18 months]

      To characterize Cmin of TTI-622.

    8. Phase 1a: Characterize the TTI-622 PK parameter Cavg [Through study completion, up to 18 months]

      To characterize Cavg of TTI-622.

    9. Phase 1a: Characterize the clearance of TTI-622 [Through study completion, up to 18 months]

      To characterize clearance of TTI-622.

    10. Phase 1a: Characterize the volume of distribution of TTI-622 [Through study completion, up to 18 months]

      To characterize volume of distribution of TTI-622.

    11. Phase 1a: Characterize the immunogenicity of TTI-622 [Through study completion, up to 18 months]

      To characterize the incidence of anti-drug antibodies (ADA).

    12. Phase 1a: Characterize the preliminary evidence of antitumor activity of TTI-622: overall response rate [Through study completion, up to 18 months]

      To determine the overall response rate (ORR) for participants treated with TTI-622.

    13. Phase 1a: Characterize the preliminary evidence of antitumor activity of TTI-622: disease control rate [Through study completion, up to 18 months]

      To determine the disease control rate (DCR) for participants treated with TTI-622.

    14. Phase 1a: Characterize the preliminary evidence of antitumor activity of TTI-622: time to response [Through study completion, up to 18 months]

      To determine the time to response (TTR) for participants treated with TTI-622.

    15. Phase 1a: Characterize the preliminary evidence of antitumor activity of TTI-622: duration of response [Through study completion, up to 18 months]

      To determine the duration of response (DOR) for participants treated with TTI-622.

    16. Phase 1a: Characterize the preliminary evidence of antitumor activity of TTI-622: progression free survival [Through study completion, up to 18 months]

      To determine the progression free survival (PFS) time for participants treated with TTI-622.

    17. Phase 1b: Characterize the TTI-622 PK parameter t1/2 when combined with selected anticancer treatments or as a single agent [Through study completion, up to 30 months]

      To characterize t1/2 of TTI-622 when combined with selected anticancer treatments or as a single agent.

    18. Phase 1b: Characterize the TTI-622 PK parameter AUC0-t when combined with selected anticancer treatments or as a single agent [Through study completion, up to 30 months]

      To characterize AUC0-t of TTI-622 when combined with selected anticancer treatments or as a single agent.

    19. Phase 1b: Characterize the TTI-622 PK parameter AUC0-tau when combined with selected anticancer treatments or as a single agent [Through study completion, up to 30 months]

      To characterize AUC0-tau of TTI-622 when combined with selected anticancer treatments or as a single agent.

    20. Phase 1b: Characterize the TTI-622 PK parameter AUC0-infinity when combined with selected anticancer treatments or as a single agent [Through study completion, up to 30 months]

      To characterize AUC0-infinity of TTI-622 when combined with selected anticancer treatments or as a single agent.

    21. Phase 1b: Characterize the TTI-622 PK parameter Tmax when combined with selected anticancer treatments or as a single agent [Through study completion, up to 30 months]

      To characterize Tmax of TTI-622 when combined with selected anticancer treatments or as a single agent.

    22. Phase 1b: Characterize the TTI-622 PK parameter Cmax when combined with selected anticancer treatments or as a single agent [Through study completion, up to 30 months]

      To characterize Cmax of TTI-622 when combined with selected anticancer treatments or as a single agent.

    23. Phase 1b: Characterize the TTI-622 PK parameter Cmin when combined with selected anticancer treatments or as a single agent [Through study completion, up to 30 months]

      To characterize Cmin of TTI-622 when combined with selected anticancer treatments or as a single agent.

    24. Phase 1b: Characterize the TTI-622 PK parameter Cavg when combined with selected anticancer treatments or as a single agent [Through study completion, up to 30 months]

      To characterize Cavg of TTI-622 when combined with selected anticancer treatments or as a single agent.

    25. Phase 1b: Characterize the clearance of TTI-622 when combined with selected anticancer treatments or as a single agent [Through study completion, up to 30 months]

      To characterize clearance of TTI-622 when combined with selected anticancer treatments or as a single agent.

    26. Phase 1b: Characterize the volume of distribution of TTI-622 when combined with selected anticancer treatments or as a single agent [Through study completion, up to 30 months]

      To characterize volume of distribution of TTI-622 when combined with selected anticancer treatments or as a single agent.

    27. Phase 1b: Characterize the immunogenicity of TTI-622 when combined with selected anticancer treatments or as a single agent [Through study completion, up to 30 months]

      To characterize the incidence of anti-drug antibodies (ADA).

    28. Phase 1b: Characterize the preliminary evidence of antitumour activity of TTI-622 when combined with selected anticancer treatments or as a single agent: disease control rate [Through study completion, up to 30 months]

      To determine the disease control rate (DCR) for participants treated with TTI-622 when combined with selected anticancer treatments or as a single agent.

    29. Phase 1b: Characterize the preliminary evidence of antitumour activity of TTI-622 when combined with selected anticancer treatments or as a single agent: time to response [Through study completion, up to 30 months]

      To determine the time to response (TTR) for participants treated with TTI-622 when combined with selected anticancer treatments or as a single agent.

    30. Phase 1b: Characterize the preliminary evidence of antitumour activity of TTI-622 when combined with selected anticancer treatments or as a single agent: event-free survival [Through study completion, up to 30 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 or as a single agent.

    31. Phase 1b: Characterize the preliminary evidence of antitumour activity of TTI-622 when combined with selected anticancer treatments or as a single agent: duration of response [Through study completion, up to 30 months]

      To determine the duration of response (DOR) for participants treated with TTI-622 when combined with selected anticancer treatments or as a single agent.

    32. Phase 1b: Characterize the preliminary evidence of antitumour activity of TTI-622 when combined with selected anticancer treatments or as a single agent: progression-free survival [Through study completion, up to 30 months]

      To determine the progression-free survival (PFS) time for participants treated with TTI-622 when combined with selected anticancer treatments or as a single agent.

    33. Phase 1b: Characterize the preliminary evidence of antitumour activity of TTI-622 when combined with selected anticancer treatments or as a single agent: minimal residual disease [Through study completion, up to 30 months]

      To determine minimal residual disease (MRD; for Cohorts A, B, C and E) for participants treated with TTI-622 when combined with selected anticancer treatments or as a single agent.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Key Inclusion Criteria (Phase 1b Cohorts C and E): Histologically documented relapsed/refractory Multiple Myeloma (MM).

    Key Inclusion Criteria (Phase 1b Cohort D): Pathologically confirmed relapsed/refractory diffuse large B-cell lymphoma (DLBCL)

    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.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1University of Southern California Norris Comprehensive Cancer CenterLos AngelesCaliforniaUnited States90033
    2Sarah Cannon Research Institute at Colorado Blood Cancer Institute (CBCI)DenverColoradoUnited States80218
    3Georgetown Lombardi Comprehensive Cancer CenterWashingtonDistrict of ColumbiaUnited States20057
    4Lakes ResearchMiami LakesFloridaUnited States33014
    5Norton HealthcareLouisvilleKentuckyUnited States40207
    6University of MichiganAnn ArborMichiganUnited States48109
    7Barbara Ann Karmanos Cancer InstituteDetroitMichiganUnited States48201
    8Montefiore Medical CenterBronxNew YorkUnited States10467
    9Roswell Park Comprehensive Cancer CenterBuffaloNew YorkUnited States14263
    10Memorial Sloan Kettering Cancer CenterNew YorkNew YorkUnited States10065
    11Gabrail Cancer Center Research, LLCCantonOhioUnited States44718
    12University of TN Medical Center/Cancer InstituteKnoxvilleTennesseeUnited States37920
    13MD Anderson Cancer CenterHoustonTexasUnited States77030
    14Swedish Cancer Institute - ResearchSeattleWashingtonUnited States98104

    Sponsors and Collaborators

    • Trillium Therapeutics Inc.

    Investigators

    • Study Director: Ingmar Bruns, MD, PhD, Trillium Therapeutics Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Trillium Therapeutics Inc.
    ClinicalTrials.gov Identifier:
    NCT03530683
    Other Study ID Numbers:
    • TTI-622-01
    First Posted:
    May 21, 2018
    Last Update Posted:
    Apr 6, 2022
    Last Verified:
    Mar 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Trillium Therapeutics Inc.
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Apr 6, 2022