A Trial of TTI-621 for Patients With Hematologic Malignancies and Selected Solid Tumors

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ClinicalTrials.gov Identifier: NCT02663518

Recruitment Status : Active, not recruiting

First Posted : January 26, 2016

Last Update Posted : July 28, 2022

Sponsor:

Information provided by (Responsible Party):

Pfizer

Study Description

Brief Summary:

Multicenter, open-label, phase 1a/1b trial of TTI-621 in subjects with relapsed or refractory hematologic malignancies and selected solid tumors.

Condition or disease	Intervention/treatment	Phase
Hematologic Malignancies Solid Tumor	Drug: TTI-621 Drug: TTI-621 plus Rituximab Drug: TTI-621 plus Nivolumab	Phase 1

Detailed Description:

This is a trial of TTI-621 in subjects with relapsed or refractory hematologic malignancies and selected solid tumors.

TTI-621 (SIRPαFc) is a soluble recombinant fusion protein created by directly linking the sequences encoding the N-terminal CD47 binding domain of human SIRPα with the Fc domain of human immunoglobulin (IgG1). TTI-621 acts by binding human CD47 and preventing it from delivering an inhibitory "do not eat" (anti phagocytic) signal to macrophages.

This trial will be conducted in 2 phases and 4 parts: Phase 1a Part 1 (escalation phase) and Phase 1b Parts 2-4 (expansion phase).

In the dose Escalation Phase (phase 1a Part 1), subjects with lymphoma will be enrolled in sequential dose cohorts to receive TTI-621 to characterize safety, tolerability, pharmacokinetics, and the maximum-tolerated dose (MTD).

In the Expansion Phase (phase 1b Parts 2-4), TTI-621 will be given to subjects with a variety of hematologic malignancies and selected solid tumors to further define safety and to characterize efficacy. In the Expansion Phase Part 2, the safety and efficacy of TTI-621 will also be assessed when it is given in combination with other anti-cancer drugs. The dose of TTI-621 to be delivered in the Expansion Phase Parts 2-3 of the study may be increased or decreased based on the subject's tolerability and on the subject's response to treatment.

In the phase 1b dose optimization of the study (Part 4), further dose escalation of TTI-621, beyond the dose determined during phase 1a dose escalation, will be pursued in patients with relapsed and/or refractory CTCL following a 3+3 escalation design and using a revised DLT criteria to further evaluate the safety and tolerability of TTI-621 at dose levels higher than the initially recommended phase 1b Parts 2-3.

Secondary objectives include further characterization of the pharmacokinetics, pharmacodynamics, and development of ADA; and to gain preliminary evidence of the anti-tumor activity of TTI-621 in subjects with a variety of hematologic malignancies and selected solid tumors. In addition, the safety of TTI-621 will be evaluated in combination with other anti-cancer agents.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	250 participants
Allocation:	Non-Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Masking Description:	Open label
Primary Purpose:	Treatment
Official Title:	A Phase 1a/1b Dose Escalation and Expansion Trial of TTI-621, a Novel Biologic Targeting CD47, in Subjects With Relapsed or Refractory Hematologic Malignancies and Selected Solid Tumors
Actual Study Start Date :	January 31, 2016
Estimated Primary Completion Date :	December 31, 2022
Estimated Study Completion Date :	December 31, 2022

Resource links provided by the National Library of Medicine

Genetic and Rare Diseases Information Center resources: Lymphosarcoma Acute Graft Versus Host Disease Peripheral T-cell Lymphoma Acute Lymphoblastic Leukemia Lymphoblastic Lymphoma Cutaneous T-cell Lymphoma

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: TTI-621 Escalation Phase The Escalation Phase will include multiple doses of TTI-621	Drug: TTI-621 Monotherapy Other Name: SIRPαFc
Experimental: Indolent B-Cell Lymphoma Monotherapy expansion cohort with TTI-621	Drug: TTI-621 Monotherapy Other Name: SIRPαFc
Experimental: Aggressive B-Cell Lymphoma Monotherapy expansion cohort with TTI-621	Drug: TTI-621 Monotherapy Other Name: SIRPαFc
Experimental: T-Cell Lymphoma Monotherapy expansion cohort with TTI-621	Drug: TTI-621 Monotherapy Other Name: SIRPαFc
Experimental: Hodgkin Lymphoma Monotherapy expansion cohort with TTI-621	Drug: TTI-621 Monotherapy Other Name: SIRPαFc
Experimental: Chronic Lymphocytic Leukemia Monotherapy expansion cohort with TTI-621	Drug: TTI-621 Monotherapy Other Name: SIRPαFc
Experimental: Acute Lymphoblastic Leukemia Monotherapy expansion cohort with TTI-621	Drug: TTI-621 Monotherapy Other Name: SIRPαFc
Experimental: Multiple Myeloma Monotherapy expansion cohort with TTI-621	Drug: TTI-621 Monotherapy Other Name: SIRPαFc
Experimental: Acute Myeloid Leukemia Monotherapy expansion cohort with TTI-621	Drug: TTI-621 Monotherapy Other Name: SIRPαFc
Experimental: Myelodysplastic Syndrome Monotherapy expansion cohort with TTI-621	Drug: TTI-621 Monotherapy Other Name: SIRPαFc
Experimental: Myeloproliferative Neoplasms Monotherapy expansion cohort with TTI-621	Drug: TTI-621 Monotherapy Other Name: SIRPαFc
Experimental: Small Cell Lung Cancer Monotherapy expansion cohort with TTI-621	Drug: TTI-621 Monotherapy Other Name: SIRPαFc
Experimental: Rituximab Combination Combination therapy expansion cohort with TTI-621 plus Rituximab for CD20 positive malignancies	Drug: TTI-621 plus Rituximab Combination therapy Other Name: TTI-621 plus Rituxan
Experimental: Nivolumab Combination Combination therapy expansion cohort with TTI-621 plus Nivolumab for Hodgkin Lymphoma	Drug: TTI-621 plus Nivolumab Combination therapy Other Name: TTI-621 plus Opdivo
Experimental: Cutaneous T-Cell Lymphoma (CTCL) Monotherapy expansion cohort with TTI-621	Drug: TTI-621 Monotherapy Other Name: SIRPαFc
Experimental: Peripheral T-Cell Lymphoma (PTCL) Monotherapy expansion cohort with TTI-621	Drug: TTI-621 Monotherapy Other Name: SIRPαFc
Experimental: Part 4: Cutaneous T-Cell Lymphoma (CTCL) Monotherapy expansion Part 4 (Dose Optimization) cohort with TTI-621	Drug: TTI-621 Monotherapy Other Name: SIRPαFc

Outcome Measures

Primary Outcome Measures :

Incidence and severity of adverse events [ Time Frame: 42 months ]
Safety and tolerability of TTI-621 when given alone and in combination with other anti-cancer agents to subjects with a variety of hematologic malignancies and with selected solid tumors, and to evaluate the safety of a standardized intra-subject TTI-621 dose intensification schedule.

Part 4: To further evaluate the safety and tolerability of TTI-621 at dose levels higher than the initially recommended phase 1b Parts 2 and 3 dose and to reassess the MTD and/or recommended phase 2 dose per revised DLT criteria following a 3+3 dose escalation schema.

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

Inclusion Criteria:

Advanced measurable malignancy
Adequate hematologic status
Relapsed or are refractory following at least 2 prior systemic therapeutic attempts (1 prior systemic attempt for PTCL). For CTCL, extracorporal photochemotherapy (ECP) will be considered a systemic therapy. Local radiation and topical agents are not systemic therapies.
Adequate coagulation function
Adequate hepatic function
Adequate renal function

Exclusion Criteria:

Known, current central nervous system disease involvement or untreated brain metastases
Allogeneic transplant within 30 days prior to the planned start of treatment or subjects with active graft-vs-host disease with the exception of Grade 1 skin involvement
History of hemolytic anemia or bleeding diathesis

Contacts and Locations

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): NCT02663518

Locations

Show 51 study locations

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United States, California
City of Hope National Medical Center
Duarte, California, United States, 91010
City of Hope
Duarte, California, United States, 91010
Freidenrich Center for Translational Research (CTRU)
Palo Alto, California, United States, 94304
Stanford Cancer Institute
Palo Alto, California, United States, 94304
United States, Colorado
Colorado Blood Cancer Institute
Denver, Colorado, United States, 80218
Presbyterian/St.Luke's Medical Center
Denver, Colorado, United States, 80218
United States, Florida
Mayo Clinic Jacksonville
Jacksonville, Florida, United States, 32224
Mayo Clinic
Jacksonville, Florida, United States, 32224
Moffitt Cancer Center Richard M Schulze Family Foundation Outpatient Center at McKinley Campus
Tampa, Florida, United States, 33612
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Indiana
Covance Biorepository
Greenfield, Indiana, United States, 46140
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, New Jersey
Hackensack Meridian Health John Theurer Cancer Center
Hackensack, New Jersey, United States, 07601
Hackensack UMC
Hackensack, New Jersey, United States, 07601
The John Theurer Cancer Center at Hackensack UMC
Hackensack, New Jersey, United States, 07601
Memorial Sloan Kettering Cancer Center- Monmouth
Middletown, New Jersey, United States, 07748
United States, New York
Memorial Sloan Kettering Cancer Center Westchester
Harrison, New York, United States, 10604
Laura and Isaac Perlmutter Cancer Center at NYU Langone Health
New York, New York, United States, 10016
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, United States, 10016
NYU Investigational Pharmacy
New York, New York, United States, 10016
NYU Langone Health (Tisch Hospital)
New York, New York, United States, 10016
Memorial Sloan Kettering Cancer Center-Clinical Trails Office
New York, New York, United States, 10017
Columbia Univeristy
New York, New York, United States, 10019
Memorial Sloan Kettering Cancer Center - David H. Koch Center for Cancer Care
New York, New York, United States, 10021
Memorial Sloan Kettering Cancer Center Rockefeller Outpatient Pavillion
New York, New York, United States, 10022
Columbia University Medical Center.
New York, New York, United States, 10032
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, Ohio
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195
Cleveland Clinic
Cleveland, Ohio, United States, 44195
United States, Oregon
Oregon Health & Science University-Research Pharmacy Services
Portland, Oregon, United States, 97239
Oregon Health & Science University
Portland, Oregon, United States, 97239
Oregon Health and Sciences University
Portland, Oregon, United States, 97239
United States, Pennsylvania
University of Pittsburgh Medical Center Presbyterian Shadyside
Pittsburgh, Pennsylvania, United States, 15213
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15237
United States, Tennessee
Centennial Medical Center
Nashville, Tennessee, United States, 37203
Sarah Cannon Research Institute (Pharmacy)
Nashville, Tennessee, United States, 37203
Tennessee Oncology PLLC
Nashville, Tennessee, United States, 37203
Tennessee Oncology, PLLC
Nashville, Tennessee, United States, 37203
Tennessee Oncology
Nashville, Tennessee, United States, 37203
United States, Texas
Myriad RMB Inc
Austin, Texas, United States, 78759
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
University of Texas MD Anderson Cancer Center, Cancer Prevention Center
Houston, Texas, United States, 77030
University of Texas MD Anderson Cancer Center, Melanoma and Skin Clinic
Houston, Texas, United States, 77030
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
University of Washington - Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
University of Washington Medical Center
Seattle, Washington, United States, 98195
Canada, B.C.
Fairmont Medical Building, Suite 810
Vancouver, B.C., Canada, V5Z1H7
Canada, British Columbia
British Columbia Cancer Agency
Vancouver, British Columbia, Canada, V5Z 1H6
Canada, Ontario
Princess Margaret Cancer Center
Toronto, Ontario, Canada, M5G 2M9
University Health Network - Princess Margaret Cancer Centre
Toronto, Ontario, Canada, M5G 2M9

Sponsors and Collaborators

Pfizer

Investigators

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Study Director:	Pfizer CT.gov Call Center	Pfizer

More Information

Additional Information:

To obtain contact information for a study center near you, click here. This link exits the ClinicalTrials.gov site

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ansell SM, Maris MB, Lesokhin AM, Chen RW, Flinn IW, Sawas A, Minden MD, Villa D, Percival MM, Advani AS, Foran JM, Horwitz SM, Mei MG, Zain J, Savage KJ, Querfeld C, Akilov OE, Johnson LDS, Catalano T, Petrova PS, Uger RA, Sievers EL, Milea A, Roberge K, Shou Y, O'Connor OA. Phase I Study of the CD47 Blocker TTI-621 in Patients with Relapsed or Refractory Hematologic Malignancies. Clin Cancer Res. 2021 Apr 15;27(8):2190-2199. doi: 10.1158/1078-0432.CCR-20-3706. Epub 2021 Jan 15.

Johnson LDS, Banerjee S, Kruglov O, Viller NN, Horwitz SM, Lesokhin A, Zain J, Querfeld C, Chen R, Okada C, Sawas A, O'Connor OA, Sievers EL, Shou Y, Uger RA, Wong M, Akilov OE. Targeting CD47 in Sézary syndrome with SIRPαFc. Blood Adv. 2019 Apr 9;3(7):1145-1153. doi: 10.1182/bloodadvances.2018030577.

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Responsible Party:	Pfizer
ClinicalTrials.gov Identifier:	NCT02663518
Other Study ID Numbers:	TTI-621-01 C4961001 ( Other Identifier: Alias Study Number )
First Posted:	January 26, 2016 Key Record Dates
Last Update Posted:	July 28, 2022
Last Verified:	July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

Keywords provided by Pfizer:


T-Cell CTCL PTCL ALL Rituximab Nivolumab TTI-621	Solid Tumor Hematologic Malignancies Lymphoma Cutaneous T-Cell Lymphoma Peripheral T-Cell Lymphoma Acute Lymphoblastic Leukemia CD47

Additional relevant MeSH terms:

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Neoplasms Hematologic Neoplasms Neoplasms by Site Hematologic Diseases Rituximab Nivolumab Immunoglobulin G	Antineoplastic Agents, Immunological Antineoplastic Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Immune Checkpoint Inhibitors Molecular Mechanisms of Pharmacological Action

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