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

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ClinicalTrials.gov Identifier: NCT03530683
Recruitment Status : Recruiting
First Posted : May 21, 2018
Last Update Posted : July 15, 2021
Sponsor:
Information provided by (Responsible Party):
Trillium Therapeutics Inc.

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 Drug: TTI-622 Drug: Azacitidine Drug: Venetoclax Drug: Carfilzomib Drug: Dexamethasone 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).

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 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 : April 30, 2022
Estimated Study Completion Date : December 30, 2022


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 C: TTI-622 + 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




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 18 months ]
    To characterize the safety profile (incidence of AEs).

  3. Phase 1b: Efficacy of each combination treatment [ Time Frame: Through study completion, up to 18 months ]
    To evaluate preliminary efficacy (response rate) of each combination treatment in the 3 Cohorts (A to C).


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 [ Time Frame: Through study completion, up to 18 months ]
    To characterize t1/2 of TTI-622 when combined with selected anticancer treatments.

  18. 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 ]
    To characterize AUC0-t of TTI-622 when combined with selected anticancer treatments.

  19. 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 ]
    To characterize AUC0-tau of TTI-622 when combined with selected anticancer treatments.

  20. 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 ]
    To characterize AUC0-infinity of TTI-622 when combined with selected anticancer treatments.

  21. Phase 1b: Characterize the TTI-622 PK parameter Tmax when combined with selected anticancer treatments [ Time Frame: Through study completion, up to 18 months ]
    To characterize Tmax of TTI-622 when combined with selected anticancer treatments.

  22. Phase 1b: Characterize the TTI-622 PK parameter Cmax when combined with selected anticancer treatments [ Time Frame: Through study completion, up to 18 months ]
    To characterize Cmax of TTI-622 when combined with selected anticancer treatments.

  23. Phase 1b: Characterize the TTI-622 PK parameter Cmin when combined with selected anticancer treatments [ Time Frame: Through study completion, up to 18 months ]
    To characterize Cmin of TTI-622 when combined with selected anticancer treatments.

  24. Phase 1b: Characterize the TTI-622 PK parameter Cavg when combined with selected anticancer treatments [ Time Frame: Through study completion, up to 18 months ]
    To characterize Cavg of TTI-622 when combined with selected anticancer treatments.

  25. Phase 1b: Characterize the clearance of TTI-622 when combined with selected anticancer treatments [ Time Frame: Through study completion, up to 18 months ]
    To characterize clearance of TTI-622 when combined with selected anticancer treatments.

  26. 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 ]
    To characterize volume of distribution of TTI-622 when combined with selected anticancer treatments.

  27. Phase 1b: Characterize the immunogenicity of TTI-622 when combined with selected anticancer treatments [ Time Frame: Through study completion, up to 18 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: 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 when combined with selected anticancer treatments.

  29. 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 ]
    To determine the time to response (TTR) for participants treated with TTI-622 when combined with selected anticancer treatments.

  30. 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 ]
    To determine event-free survival (EFS; for Cohorts A and B) time for participants treated with TTI-622 when combined with selected anticancer treatments.

  31. 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 ]
    To determine the duration of response (DOR) for participants treated with TTI-622 when combined with selected anticancer treatments.

  32. 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 ]
    To determine the progression-free survival (PFS) time for participants treated with TTI-622 when combined with selected anticancer treatments.



Information from the National Library of Medicine

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.


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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.

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.

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: Kathleen Large, RN, MSN 875-412-7029 ext 211 kathleen2@trilliumtherapeutics.com
Contact: Amirah Shahin amirah@trilliumtherapeutics.com

Locations
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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      
United States, District of Columbia
Georgetown Lombardi Comprehensive Cancer Center Recruiting
Washington, District of Columbia, United States, 20057
Contact: Jeanette Crawford       crawforjg@georgetown.edu   
United States, Florida
Lakes Research Withdrawn
Miami Lakes, Florida, United States, 33014
United States, Michigan
Barbara Ann Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Eliza Bourke    313-576-9698    bourkee@Karmanos.org   
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Tala Shekarkt    646-449-1351    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.
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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: July 15, 2021
Last Verified: July 2021
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
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
Neoplasms by Site
Dexamethasone
Azacitidine
Venetoclax
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones