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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
Sponsor:
Information provided by (Responsible Party):
Trillium Therapeutics Inc.

Study Description
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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.

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

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
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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

Resource links provided by the National Library of Medicine


Arms and Interventions
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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


Outcome Measures
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Primary Outcome Measures :
  1. 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.

  2. Phase 1b: Frequency and severity of AEs [ Time Frame: Through study completion, up to 30 months ]
    To characterize the safety profile (incidence of AEs).

  3. 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).

  4. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

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

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

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

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

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

  10. 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.

  11. 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).

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  21. 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.

  22. 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.

  23. 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.

  24. 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.

  25. 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.

  26. 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.

  27. 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).

  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 [ 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.

  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 [ 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.

  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 [ 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.

  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 [ 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.

  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 [ 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.

  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 [ 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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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
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Information from the National Library of Medicine

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


Contacts
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Contact: Naomi Molloy 416-595-0627 ext 282 naomi@trilliumtherapeutics.com
Contact: Alex Tankelevich alex@trilliumtherapeutics.com

Locations
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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   
Sponsors and Collaborators
Trillium Therapeutics Inc.
Investigators
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Study Director: Ingmar Bruns, MD, PhD Trillium Therapeutics Inc.
More Information
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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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Trillium Therapeutics Inc.:
Neoplasms
Lymphoma
Myeloma
Leukemia
Additional relevant MeSH terms:
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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