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.
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
Drug | Synonyms | Arms |
---|
TTI-622 | SIRPα-IgG4 Fc | Cohort A: TTI-622 + Azacitidine |
Azacitidine | VIDAZA | Cohort A: TTI-622 + Azacitidine |
Venetoclax | VENCLEXTA | Cohort B: TTI-622 + Azacitidine and Venetoclax |
Carfilzomib | KYPROLIS | Cohort C: TTI-622 + Carfilzomib and Dexamethasone |
Dexamethasone | | Cohort 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
Name | Type | Description | Interventions |
---|
TTI-622 Monotherapy | Experimental | | |
Cohort A: TTI-622 + Azacitidine | Experimental | | |
Cohort B: TTI-622 + Azacitidine and Venetoclax | Experimental | | - TTI-622
- Azacitidine
- Venetoclax
|
Cohort C: TTI-622 + Carfilzomib and Dexamethasone | Experimental | | - 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