A Trial of TTI-622 in Patients With Advanced Hematologic Malignancies (TTI-622-01)
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT03530683 |
Recruitment Status :
Recruiting
First Posted : May 21, 2018
Last Update Posted : May 19, 2022
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Lymphoma Multiple Myeloma Acute Myeloid Leukemia Diffuse Large B-Cell Lymphoma | Drug: TTI-622 Drug: Azacitidine Drug: Venetoclax Drug: Carfilzomib Drug: Dexamethasone Drug: anti-CD20 Targeting agent | Phase 1 |
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 Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 350 participants |
Allocation: | Non-Randomized |
Intervention Model: | Sequential Assignment |
Intervention Model Description: | Parallel 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 |
Estimated Primary Completion Date : | June 30, 2023 |
Estimated Study Completion Date : | June 30, 2024 |

Arm | Intervention/treatment |
---|---|
Experimental: TTI-622 Monotherapy |
Drug: TTI-622
TTI-622 will be administered by intravenous infusion.
Other Name: SIRPα-IgG4 Fc |
Experimental: Cohort A: TTI-622 + Azacitidine |
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 |
Experimental: Cohort B: TTI-622 + Azacitidine and Venetoclax |
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 |
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 Name: 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 Name: 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 Name: SIRPα-IgG4 Fc Drug: anti-CD20 Targeting agent 375 mg/m^2 weekly for up to eight doses
Other Name: 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 Name: SIRPα-IgG4 Fc |
- 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 30 months ]To characterize the safety profile (incidence of AEs).
- Phase 1b: Efficacy of each combination treatment [ Time Frame: 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).
- Phase 1b: Recommended dose of TTI-622 [ Time Frame: Through study completion, up to 30 months ]To determine the recommended dose of TTI-622 as a single agent.
- 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 or as a single agent [ Time Frame: 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.
- Phase 1b: Characterize the TTI-622 PK parameter AUC0-t when combined with selected anticancer treatments or as a single agent [ Time Frame: 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.
- Phase 1b: Characterize the TTI-622 PK parameter AUC0-tau when combined with selected anticancer treatments or as a single agent [ Time Frame: 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.
- Phase 1b: Characterize the TTI-622 PK parameter AUC0-infinity when combined with selected anticancer treatments or as a single agent [ Time Frame: 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.
- Phase 1b: Characterize the TTI-622 PK parameter Tmax when combined with selected anticancer treatments or as a single agent [ Time Frame: Through study completion, up to 30 months ]To characterize Tmax of TTI-622 when combined with selected anticancer treatments or as a single agent.
- Phase 1b: Characterize the TTI-622 PK parameter Cmax when combined with selected anticancer treatments or as a single agent [ Time Frame: Through study completion, up to 30 months ]To characterize Cmax of TTI-622 when combined with selected anticancer treatments or as a single agent.
- Phase 1b: Characterize the TTI-622 PK parameter Cmin when combined with selected anticancer treatments or as a single agent [ Time Frame: Through study completion, up to 30 months ]To characterize Cmin of TTI-622 when combined with selected anticancer treatments or as a single agent.
- Phase 1b: Characterize the TTI-622 PK parameter Cavg when combined with selected anticancer treatments or as a single agent [ Time Frame: Through study completion, up to 30 months ]To characterize Cavg of TTI-622 when combined with selected anticancer treatments or as a single agent.
- Phase 1b: Characterize the clearance of TTI-622 when combined with selected anticancer treatments or as a single agent [ Time Frame: Through study completion, up to 30 months ]To characterize clearance of TTI-622 when combined with selected anticancer treatments or as a single agent.
- Phase 1b: Characterize the volume of distribution of TTI-622 when combined with selected anticancer treatments or as a single agent [ Time Frame: 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.
- Phase 1b: Characterize the immunogenicity of TTI-622 when combined with selected anticancer treatments or as a single agent [ Time Frame: Through study completion, up to 30 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 or as a single agent: disease control rate [ Time Frame: 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.
- 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 [ Time Frame: 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.
- 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 [ Time Frame: 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.
- 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 [ Time Frame: 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.
- 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 [ Time Frame: 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.
- 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 [ Time Frame: 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.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Key Inclusion Criteria (Phase 1a and Phase 1b, all Cohorts):
- Available fresh or archived tumor tissue.
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
- Adequate coagulation function.
- Adequate hepatic function.
- Adequate hematologic status.
- Adequate renal function.
- 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):
- Known, current central nervous system disease involvement.
- 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).
- Subjects who have undergone radiation therapy within 14 days of study treatment administration.
- 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.
- Major surgery within 30 days before planned start of study treatment.

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): NCT03530683
Contact: Naomi Molloy | 416-595-0627 ext 282 | naomi@trilliumtherapeutics.com | |
Contact: Alex Tankelevich | alex@trilliumtherapeutics.com |
United States, California | |
University of Southern California Norris Comprehensive Cancer Center | Recruiting |
Los Angeles, California, United States, 90033 | |
Contact: Jenny Zeng 323-865-0840 jenny.zeng@med.usc.edu | |
United States, Colorado | |
Sarah Cannon Research Institute at Colorado Blood Cancer Institute (CBCI) | Recruiting |
Denver, Colorado, United States, 80218 | |
Contact: Ben Burtness 720-754-8064 ben.burtness@sarahcannon.com | |
United States, District of Columbia | |
Georgetown Lombardi Comprehensive Cancer Center | Recruiting |
Washington, District of Columbia, United States, 20057 | |
Contact: Melin Vranesic 202-687-0160 mv764@georgetown.edu | |
United States, Florida | |
Lakes Research | Withdrawn |
Miami Lakes, Florida, United States, 33014 | |
United States, Georgia | |
Northside Hospital | Recruiting |
Atlanta, Georgia, United States, 30342 | |
Contact: Adriane Strong 404-300-2296 Adriane.Strong@northside.com | |
United States, Kentucky | |
Norton Healthcare | Recruiting |
Louisville, Kentucky, United States, 40207 | |
Contact: Dana Rees, RN, BSN, OCN 502-899-3366 ext 19281 dana.rees@nortonhealthcare.org | |
United States, Michigan | |
University of Michigan | Recruiting |
Ann Arbor, Michigan, United States, 48109 | |
Contact: Erica Chapman 734-232-0716 echapman@med.umich.edu | |
Barbara Ann Karmanos Cancer Institute | Recruiting |
Detroit, Michigan, United States, 48201 | |
Contact: Megi Gojka 313-576-9685 gojkam@karmanos.org | |
United States, New York | |
Montefiore Medical Center | Recruiting |
Bronx, New York, United States, 10467 | |
Contact: Karen Fehn, CCRP kfehn@montefiore.org | |
Roswell Park Comprehensive Cancer Center | Recruiting |
Buffalo, New York, United States, 14263 | |
Contact: Jennifer Walker Jennifer.walker@roswellpark.org | |
Memorial Sloan Kettering Cancer Center | Recruiting |
New York, New York, United States, 10065 | |
Contact: Tala Shekarkhand 646-608-3915 shekarkt@mskcc.org | |
United States, Ohio | |
Gabrail Cancer Center Research, LLC | Terminated |
Canton, Ohio, United States, 44718 | |
United States, Tennessee | |
University of TN Medical Center/Cancer Institute | Recruiting |
Knoxville, Tennessee, United States, 37920 | |
Contact: Krissy Bollig, RN, BSN 865-305-7469 klbollig@utmck.edu | |
United States, Texas | |
MD Anderson Cancer Center | Recruiting |
Houston, Texas, United States, 77030 | |
Contact: Karen Peyton, RN, BSN, OCN 713-745-8923 kfpeyton@mdanderson.org | |
United States, Washington | |
Swedish Cancer Institute - Research | Recruiting |
Seattle, Washington, United States, 98104 | |
Contact: Krystle Pagarigan 206-386-2098 krystle.pagarigan@swedish.org |
Study Director: | Ingmar Bruns, MD, PhD | Trillium Therapeutics Inc. |
Responsible Party: | Trillium Therapeutics Inc. |
ClinicalTrials.gov Identifier: | NCT03530683 |
Other Study ID Numbers: |
TTI-622-01 |
First Posted: | May 21, 2018 Key Record Dates |
Last Update Posted: | May 19, 2022 |
Last Verified: | May 2022 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Neoplasms Lymphoma Myeloma Leukemia |
Lymphoma Leukemia Multiple Myeloma Neoplasms, Plasma Cell Lymphoma, Large B-Cell, Diffuse Hematologic Neoplasms Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Hemostatic Disorders Vascular Diseases Cardiovascular Diseases |
Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoma, B-Cell Lymphoma, Non-Hodgkin Neoplasms by Site Dexamethasone Azacitidine Venetoclax Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs |