Clinical Trials /

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

NCT03530683

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
  • Lymphoma
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Trial of TTI-622 in Patients With Advanced Hematologic Malignancies
  • 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

Clinical Trial IDs

  • ORG STUDY ID: TTI-622-01
  • NCT ID: NCT03530683

Conditions

  • Lymphoma
  • Multiple Myeloma
  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
TTI-622SIRPα-IgG4 FcCohort A: TTI-622 + Azacitidine
AzacitidineVIDAZACohort A: TTI-622 + Azacitidine
VenetoclaxVENCLEXTACohort B: TTI-622 + Azacitidine and Venetoclax
CarfilzomibKYPROLISCohort C: TTI-622 + Carfilzomib and Dexamethasone
DexamethasoneCohort C: TTI-622 + Carfilzomib and Dexamethasone

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
TTI-622 MonotherapyExperimental
  • TTI-622
Cohort A: TTI-622 + AzacitidineExperimental
  • TTI-622
  • Azacitidine
Cohort B: TTI-622 + Azacitidine and VenetoclaxExperimental
  • TTI-622
  • Azacitidine
  • Venetoclax
Cohort C: TTI-622 + Carfilzomib and DexamethasoneExperimental
  • TTI-622
  • Carfilzomib
  • Dexamethasone

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1a: Frequency and severity of adverse events (AEs)
Time Frame:Through study completion, up to 18 months
Safety Issue:
Description:To characterize the safety profile (incidence of AEs) and dose-limiting toxicities (DLTs) of TTI-622.

Secondary Outcome Measures

Measure:Phase 1a: Characterize the TTI-622 pharmacokinetics (PK) parameter t1/2
Time Frame:Through study completion, up to 18 months
Safety Issue:
Description:To characterize t1/2 of TTI-622.
Measure:Phase 1a: Characterize the TTI-622 PK parameter AUC0-t
Time Frame:Through study completion, up to 18 months
Safety Issue:
Description:To characterize AUC0-t of TTI-622.
Measure:Phase 1a: Characterize the TTI-622 PK parameter AUC0-tau
Time Frame:Through study completion, up to 18 months
Safety Issue:
Description:To characterize AUC0-tau of TTI-622.
Measure:Phase 1a: Characterize the TTI-622 PK parameter AUC0-infinity
Time Frame:Through study completion, up to 18 months
Safety Issue:
Description:To characterize AUC0-infinity of TTI-622.
Measure:Phase 1a: Characterize the TTI-622 PK parameter Tmax
Time Frame:Through study completion, up to 18 months
Safety Issue:
Description:To characterize Tmax of TTI-622.
Measure:Phase 1a: Characterize the TTI-622 PK parameter Cmax
Time Frame:Through study completion, up to 18 months
Safety Issue:
Description:To characterize Cmax of TTI-622.
Measure:Phase 1a: Characterize the TTI-622 PK parameter Cmin
Time Frame:Through study completion, up to 18 months
Safety Issue:
Description:To characterize Cmin of TTI-622.
Measure:Phase 1a: Characterize the TTI-622 PK parameter Cavg
Time Frame:Through study completion, up to 18 months
Safety Issue:
Description:To characterize Cavg of TTI-622.
Measure:Phase 1a: Characterize the clearance of TTI-622
Time Frame:Through study completion, up to 18 months
Safety Issue:
Description:To characterize clearance of TTI-622.
Measure:Phase 1a: Characterize the volume of distribution of TTI-622
Time Frame:Through study completion, up to 18 months
Safety Issue:
Description:To characterize volume of distribution of TTI-622.
Measure:Phase 1a: Characterize the immunogenicity of TTI-622
Time Frame:Through study completion, up to 18 months
Safety Issue:
Description:To characterize the incidence of anti-drug antibodies (ADA).
Measure:Phase 1a: Characterize the preliminary evidence of antitumor activity of TTI-622: overall response rate
Time Frame:Through study completion, up to 18 months
Safety Issue:
Description:To determine the overall response rate (ORR) for participants treated with TTI-622.
Measure:Phase 1a: Characterize the preliminary evidence of antitumor activity of TTI-622: disease control rate
Time Frame:Through study completion, up to 18 months
Safety Issue:
Description:To determine the disease control rate (DCR) for participants treated with TTI-622.
Measure:Phase 1a: Characterize the preliminary evidence of antitumor activity of TTI-622: time to response
Time Frame:Through study completion, up to 18 months
Safety Issue:
Description:To determine the time to response (TTR) for participants treated with TTI-622.
Measure:Phase 1a: Characterize the preliminary evidence of antitumor activity of TTI-622: duration of response
Time Frame:Through study completion, up to 18 months
Safety Issue:
Description:To determine the duration of response (DOR) for participants treated with TTI-622.
Measure:Phase 1a: Characterize the preliminary evidence of antitumor activity of TTI-622: progression free survival
Time Frame:Through study completion, up to 18 months
Safety Issue:
Description:To determine the progression free survival (PFS) time for participants treated with TTI-622.
Measure: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
Safety Issue:
Description:To characterize t1/2 of TTI-622 when combined with selected anticancer treatments.
Measure: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
Safety Issue:
Description:To characterize AUC0-t of TTI-622 when combined with selected anticancer treatments.
Measure: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
Safety Issue:
Description:To characterize AUC0-tau of TTI-622 when combined with selected anticancer treatments.
Measure: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
Safety Issue:
Description:To characterize AUC0-infinity of TTI-622 when combined with selected anticancer treatments.
Measure:Phase 1b: Characterize the TTI-622 PK parameter Tmax when combined with selected anticancer treatments
Time Frame:Through study completion, up to 18 months
Safety Issue:
Description:To characterize Tmax of TTI-622 when combined with selected anticancer treatments.
Measure:Phase 1b: Characterize the TTI-622 PK parameter Cmax when combined with selected anticancer treatments
Time Frame:Through study completion, up to 18 months
Safety Issue:
Description:To characterize Cmax of TTI-622 when combined with selected anticancer treatments.
Measure:Phase 1b: Characterize the TTI-622 PK parameter Cmin when combined with selected anticancer treatments
Time Frame:Through study completion, up to 18 months
Safety Issue:
Description:To characterize Cmin of TTI-622 when combined with selected anticancer treatments.
Measure:Phase 1b: Characterize the TTI-622 PK parameter Cavg when combined with selected anticancer treatments
Time Frame:Through study completion, up to 18 months
Safety Issue:
Description:To characterize Cavg of TTI-622 when combined with selected anticancer treatments.
Measure:Phase 1b: Characterize the clearance of TTI-622 when combined with selected anticancer treatments
Time Frame:Through study completion, up to 18 months
Safety Issue:
Description:To characterize clearance of TTI-622 when combined with selected anticancer treatments.
Measure: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
Safety Issue:
Description:To characterize volume of distribution of TTI-622 when combined with selected anticancer treatments.
Measure:Phase 1b: Characterize the immunogenicity of TTI-622 when combined with selected anticancer treatments
Time Frame:Through study completion, up to 18 months
Safety Issue:
Description:To characterize the incidence of anti-drug antibodies (ADA).
Measure: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
Safety Issue:
Description:To determine the disease control rate (DCR) for participants treated with TTI-622 when combined with selected anticancer treatments.
Measure: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
Safety Issue:
Description:To determine the time to response (TTR) for participants treated with TTI-622 when combined with selected anticancer treatments.
Measure: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
Safety Issue:
Description:To determine event-free survival (EFS; for Cohorts A and B) time for participants treated with TTI-622 when combined with selected anticancer treatments.
Measure: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
Safety Issue:
Description:To determine the duration of response (DOR) for participants treated with TTI-622 when combined with selected anticancer treatments.
Measure: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
Safety Issue:
Description:To determine the progression-free survival (PFS) time for participants treated with TTI-622 when combined with selected anticancer treatments.

Details

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

Trial Keywords

  • Neoplasms
  • Lymphoma
  • Myeloma
  • Leukemia

Last Updated

July 15, 2021