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

Sponsor

Pfizer (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT02663518

Collaborator

(none)

250

Enrollment

Locations

Arms

Anticipated Duration (Months)

4.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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

Study Type:

Interventional

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 :

Jan 31, 2016

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

Dec 31, 2022

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 Names: SIRPαFc
Experimental: Indolent B-Cell Lymphoma Monotherapy expansion cohort with TTI-621	Drug: TTI-621 Monotherapy Other Names: SIRPαFc
Experimental: Aggressive B-Cell Lymphoma Monotherapy expansion cohort with TTI-621	Drug: TTI-621 Monotherapy Other Names: SIRPαFc
Experimental: T-Cell Lymphoma Monotherapy expansion cohort with TTI-621	Drug: TTI-621 Monotherapy Other Names: SIRPαFc
Experimental: Hodgkin Lymphoma Monotherapy expansion cohort with TTI-621	Drug: TTI-621 Monotherapy Other Names: SIRPαFc
Experimental: Chronic Lymphocytic Leukemia Monotherapy expansion cohort with TTI-621	Drug: TTI-621 Monotherapy Other Names: SIRPαFc
Experimental: Acute Lymphoblastic Leukemia Monotherapy expansion cohort with TTI-621	Drug: TTI-621 Monotherapy Other Names: SIRPαFc
Experimental: Multiple Myeloma Monotherapy expansion cohort with TTI-621	Drug: TTI-621 Monotherapy Other Names: SIRPαFc
Experimental: Acute Myeloid Leukemia Monotherapy expansion cohort with TTI-621	Drug: TTI-621 Monotherapy Other Names: SIRPαFc
Experimental: Myelodysplastic Syndrome Monotherapy expansion cohort with TTI-621	Drug: TTI-621 Monotherapy Other Names: SIRPαFc
Experimental: Myeloproliferative Neoplasms Monotherapy expansion cohort with TTI-621	Drug: TTI-621 Monotherapy Other Names: SIRPαFc
Experimental: Small Cell Lung Cancer Monotherapy expansion cohort with TTI-621	Drug: TTI-621 Monotherapy Other Names: 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 Names: 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 Names: TTI-621 plus Opdivo
Experimental: Cutaneous T-Cell Lymphoma (CTCL) Monotherapy expansion cohort with TTI-621	Drug: TTI-621 Monotherapy Other Names: SIRPαFc
Experimental: Peripheral T-Cell Lymphoma (PTCL) Monotherapy expansion cohort with TTI-621	Drug: TTI-621 Monotherapy Other Names: SIRPαFc
Experimental: Part 4: Cutaneous T-Cell Lymphoma (CTCL) Monotherapy expansion Part 4 (Dose Optimization) cohort with TTI-621	Drug: TTI-621 Monotherapy Other Names: SIRPαFc

Outcome Measures

Primary Outcome Measures

Incidence and severity of adverse events [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

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	City of Hope National Medical Center	Duarte	California	United States	91010
2	City of Hope	Duarte	California	United States	91010
3	Freidenrich Center for Translational Research (CTRU)	Palo Alto	California	United States	94304
4	Stanford Cancer Institute	Palo Alto	California	United States	94304
5	Colorado Blood Cancer Institute	Denver	Colorado	United States	80218
6	Presbyterian/St.Luke's Medical Center	Denver	Colorado	United States	80218
7	Mayo Clinic Jacksonville	Jacksonville	Florida	United States	32224
8	Mayo Clinic	Jacksonville	Florida	United States	32224
9	Moffitt Cancer Center Richard M Schulze Family Foundation Outpatient Center at McKinley Campus	Tampa	Florida	United States	33612
10	Moffitt Cancer Center	Tampa	Florida	United States	33612
11	Covance Biorepository	Greenfield	Indiana	United States	46140
12	Mayo Clinic	Rochester	Minnesota	United States	55905
13	Hackensack Meridian Health John Theurer Cancer Center	Hackensack	New Jersey	United States	07601
14	Hackensack UMC	Hackensack	New Jersey	United States	07601
15	The John Theurer Cancer Center at Hackensack UMC	Hackensack	New Jersey	United States	07601
16	Memorial Sloan Kettering Cancer Center- Monmouth	Middletown	New Jersey	United States	07748
17	Memorial Sloan Kettering Cancer Center Westchester	Harrison	New York	United States	10604
18	Laura and Isaac Perlmutter Cancer Center at NYU Langone Health	New York	New York	United States	10016
19	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York	United States	10016
20	NYU Investigational Pharmacy	New York	New York	United States	10016
21	NYU Langone Health (Tisch Hospital)	New York	New York	United States	10016
22	Memorial Sloan Kettering Cancer Center-Clinical Trails Office	New York	New York	United States	10017
23	Columbia Univeristy	New York	New York	United States	10019
24	Memorial Sloan Kettering Cancer Center - David H. Koch Center for Cancer Care	New York	New York	United States	10021
25	Memorial Sloan Kettering Cancer Center Rockefeller Outpatient Pavillion	New York	New York	United States	10022
26	Columbia University Medical Center.	New York	New York	United States	10032
27	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
28	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195
29	Cleveland Clinic	Cleveland	Ohio	United States	44195
30	Oregon Health & Science University-Research Pharmacy Services	Portland	Oregon	United States	97239
31	Oregon Health & Science University	Portland	Oregon	United States	97239
32	Oregon Health and Sciences University	Portland	Oregon	United States	97239
33	University of Pittsburgh Medical Center Presbyterian Shadyside	Pittsburgh	Pennsylvania	United States	15213
34	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15237
35	Centennial Medical Center	Nashville	Tennessee	United States	37203
36	Sarah Cannon Research Institute (Pharmacy)	Nashville	Tennessee	United States	37203
37	Tennessee Oncology PLLC	Nashville	Tennessee	United States	37203
38	Tennessee Oncology, PLLC	Nashville	Tennessee	United States	37203
39	Tennessee Oncology	Nashville	Tennessee	United States	37203
40	Myriad RMB Inc	Austin	Texas	United States	78759
41	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
42	University of Texas MD Anderson Cancer Center, Cancer Prevention Center	Houston	Texas	United States	77030
43	University of Texas MD Anderson Cancer Center, Melanoma and Skin Clinic	Houston	Texas	United States	77030
44	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
45	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
46	University of Washington - Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
47	University of Washington Medical Center	Seattle	Washington	United States	98195
48	Fairmont Medical Building, Suite 810	Vancouver	B.C.	Canada	V5Z1H7
49	British Columbia Cancer Agency	Vancouver	British Columbia	Canada	V5Z 1H6
50	Princess Margaret Cancer Center	Toronto	Ontario	Canada	M5G 2M9
51	University Health Network - Princess Margaret Cancer Centre	Toronto	Ontario	Canada	M5G 2M9