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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT03530683
Other study ID # TTI-622-01
Secondary ID C4971001
Status Active, not recruiting
Phase Phase 1
First received
Last updated
Start date June 7, 2018
Est. completion date September 11, 2024

Study information

Verified date December 2023
Source Pfizer
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The purpose of this clinical trial is to learn how the experimental medicine maplirpacept (PF-07901801) affects people with various types of blood cancers: - relapsed or refractory (R/R) lymphoma - multiple myeloma - newly diagnosed acute myeloid leukemia (AML). This trial will be conducted in the outpatient setting in 2 parts, phase 1a and phase 1b. You may only participate in one part of the study. During phase 1a of this study, we will explore how much maplirpacept (PF-07901801), when used by itself, can be safely used. If you have lymphoma, the study medicine maplirpacept (PF-07901801) will be given by infusion through a vein once a week or once every 2 weeks or every 3 weeks as determined by your doctor. Following your first dose, you will be expected to come back twice more the first week. From week 2, you will have weekly visits for blood tests, questions about your medications, any side effects, or illnesses you may have experienced and your cancer response. After you have completed 21 days (for every week dosing) or 42 days (for every 2- or 3-weeks dosing), your doctor will discuss whether you should stop study treatment or continue. If you continue, you will be expected to come back weekly for blood tests, vital signs, a brief physical exam, asked about any side effects or illnesses you may have experienced and medications you may be taking. The dosing schedule you are assigned to will continue until your disease has worsened, significant side effects occur or other reasons that lead you and your doctor to decide treatment may be stopped. To be eligible for the first part of the study you must be 18 years or older, your disease has worsened after receiving other medicines approved for blood cancer, no other treatment options exist for you, a sample of your tissue for exploratory research which can be taken from tissue already obtained or if necessary, a new sample of your tissue will be taken so your disease may be seen and measured on routine tests/scans. If you have had radiation therapy or received any anticancer medication within 14 days before the planned start of study treatment your doctor will let you know if you are eligible to participate in the study. If you have had major surgery within 30 days before the planned start of study treatment you may not be eligible to participate. The phase 1a part of the study may last up to 51/2 years. How long you participate in this study depends on side effects you may have to the study drug. It also depends on how your cancer responds to the study drug. Therefore, you may remain in the study as long as you and your study doctor think you may benefit. However, you are free to stop taking part in this study at any time and for any reason. During phase 1b part of this study, we will explore how much maplirpacept (PF-07901801), when used with other anticancer medicine(s), can be safe and reduce cancer growth. In the phase 1b part of this study, you will receive maplirpacept (PF-07901801) and other anticancer medicine(s). Which medicine combination you will receive depends on the types of cancer under treatment. Your treatment experiences will be examined to determine if maplirpacept (PF-07901801) when given with other anticancer medicine(s), is safe and can reduce cancer growth. To be eligible for the second part of the study you may have newly diagnosed Acute Myelocytic Leukemia with or without a genetic mutation or you have Multiple Myeloma or Diffuse Large B Cell Lymphoma, and your disease has worsened. The Phase 1b part of this study may last as long as you and your study doctor think you may benefit which could be up to approximately 31/2 years. How long you participate in this study depends on side effects you may have to the study drug. It also depends on how your cancer responds to the study drug. Therefore, you may remain in the study as long as you and your study doctor think you may benefit. However, you are free to stop taking part in this study at any time and for any reason.


Description:

This is a trial of maplirpacept (PF-07901801) 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 maplirpacept (PF-07901801) and Phase 1b maplirpacept (PF-07901801) Combinations and Single-Agent. In the Dose-Escalation Phase for Single-Agent maplirpacept (PF-07901801), 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 14 cohorts: (Cohort A1 and A2) subjects with newly diagnosed TP53-mutated AML will be treated with maplirpacept (PF-07901801) + azacitidine; (Cohort B1 and B2) elderly subjects or subjects unfit for intensive induction chemotherapies with newly diagnosed TP53-wildtype AML will be treated with maplirpacept (PF-07901801) + azacitidine and venetoclax; (Cohort C1, C2, and C3) subjects with relapsed or refractory MM will be treated with maplirpacept (PF-07901801) + carfilzomib and dexamethasone;(Cohort D1 and D2) subjects in relapsed or refractory CD20+ diffuse large B-cell lymphoma will be treated with maplirpacept (PF-07901801) + an anti-CD20 targeting agent; (Cohort E1 and E2) subjects with relapsed refractory MM will be treated with single-agent maplirpacept (PF-07901801); and (Cohorts F1, F2 and F3) with relapsing or refractory MM will be treated with increasing doses of maplirpacept (PF-07901801) + isatuximab, carfilzomib and dexamethasone.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 177
Est. completion date September 11, 2024
Est. primary completion date September 11, 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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, transfusion- independent lymphoma (Hodgkin or non-Hodgkin) per the 2014 Lugano classification. Key Inclusion Criteria (Phase 1b Cohort A1 and A2): Histologically confirmed, newly diagnosed TP53-mutated Acute Myeloid Leukemia (AML). Key Inclusion Criteria (Phase 1b Cohort B1 and B2): Histologically confirmed, newly diagnosed TP53-wildtype AML, elderly or unfit for more aggressive treatment. Key Inclusion Criteria (Phase 1b Cohorts C1, C2, C3 and E1, E2, F1, F2, F3): Histologically documented relapsed/refractory Multiple Myeloma (MM). Key Inclusion Criteria (Phase 1b Cohort D1 and D2): 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.

Study Design


Intervention

Drug:
Maplirpacept (PF-07901801)
maplirpacept (PF-07901801) will be administered by intravenous infusion at ranging doses, as determined from sequential dosing cohorts.
Azacitidine
intravenous (IV) or subcutaneous (SC) daily for 7 days, repeated every 4 weeks
Venetoclax
orally daily for each day of each cycle (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
Carfilzomib
Days 1, 8, and 15 of 28-day cycles; starting dose IV given on Cycle (C) 1 Day (D) 1, and if tolerated, then increased dose via IV given starting on C1D8 and subsequent doses thereafter.
Dexamethasone
starting dose via IV on Days 1, 8, 15, and increased dose via IV on 28-day cycles
Anti-CD20 Targeting agent
Days 1,8,15, and 22 of the first 28-day cycle and then on Day 1 of subsequent 21-day cycles. The anti-CD20 targeting agent will be administered for a total of eight doses, and then Cohort F1, F2 and F3: TTI-622 + isatuximab, carfilzomib and dexamethasone Cohort C1, C2 and C3: TTI-622 + Carfilzomib and Dexamethasone will be continued as single-agent therapy.
Isatuximab
F1: IV dose C0D1, C0D8, C0D15 and C0D22 (lead in phase);weekly during Cycle 1; Cycle 2 and beyond will be administered on Days 1 and 15 (Q2W). F2 and F3: IV dose C0D1 and C0D8 (lead in phase); C1D1, C1D8, C1D15 and C1D22; Cycle 2 and beyond will be administered on days 1 and 15 (Q2W). Carfilzomib: IV dose on days 1 and 2 of cycle 1; then increased IV dose on days 8, 9, 15, and 16 of cycle 1; cycle 2 and beyond: increased IV dose on days 1, 2, 8, 9, 15, and 16. Dexamethasone IV or PO on days 1, 2, 8, 9, 15, 16, 22, and 23 starting cycle 1.

Locations

Country Name City State
United States University of Michigan Ann Arbor Michigan
United States University of Michigan Hospitals Ann Arbor Michigan
United States Blood and Marrow Transplant Group of Georgia Atlanta Georgia
United States Northside Hospital Atlanta Georgia
United States Memorial Sloan Kettering Cancer Center at Basking Ridge Basking Ridge New Jersey
United States Montefiore Medical Center Bronx New York
United States Roswell Park Cancer Institute Buffalo New York
United States Gabrail Cancer Center Research Canton Ohio
United States Novant Health Cancer Institute - Research Office Charlotte North Carolina
United States Novant Health Cancer Institute Hematology - Charlotte Charlotte North Carolina
United States Novant Health Presbyterian Medical Center Charlotte North Carolina
United States Memorial Sloan Kettering Cancer Center at Commack Commack New York
United States Colorado Blood Cancer Institute Denver Colorado
United States HealthONE Presbyterian/St. Luke's Medical Center Denver Colorado
United States Barbara Ann Karmanos Cancer Institute Detroit Michigan
United States Karmanos Cancer Institute Weisberg Cancer Treatment Center Farmington Hills Michigan
United States Summit Medical Group Cancer Center Florham Park New Jersey
United States Prisma Health, Institute for Translational Oncology Research, Clinical Research Unit Greenville South Carolina
United States Prisma Health-Upstate Cancer Institute Greenville South Carolina
United States Memorial Sloan Kettering Cancer Center at Westchester Harrison New York
United States Oncology Consultants P.A. Houston Texas
United States The University of Texas MD Anderson Cancer Center Houston Texas
United States Indiana Blood & Marrow Transplantation Indianapolis Indiana
United States Indiana Blood and Marrow Transplantation-Administrative Offices Indianapolis Indiana
United States Indiana Blood and Marrow Transplantation-Clinic Indianapolis Indiana
United States University of TN Medical Center Knoxville Tennessee
United States Memorial Sloan Kettering Cancer Center - Investigational Drug Service Pharmacy Long Island City New York
United States Keck Hospital of USC Los Angeles California
United States LAC+USC Medical Center Los Angeles California
United States USC/Norris Comprehensive Cancer Center Los Angeles California
United States Norton Cancer Institute, St Matthews Campus Louisville Kentucky
United States Norton Cancer Institute, St. Matthews Campus, Attn. Becky Champion, PharmD Louisville Kentucky
United States Norton Diagnostic Center-Dupont (PET Scans) Louisville Kentucky
United States Norton Women & Children's Hospital Louisville Kentucky
United States Memorial Sloan Kettering Cancer Center at Monmouth Middletown New Jersey
United States Memorial Sloan Kettering Bergen Montvale New Jersey
United States Memorial Sloan Kettering Cancer Center at Montvale Montvale New Jersey
United States Memorial Sloan Kettering Cancer Center New York New York
United States Memorial Sloan Kettering Cancer Center (Outpatient Center) New York New York
United States Memorial Sloan Kettering Cancer Center - David H. Koch Center New York New York
United States Christiana Care Health Services Newark Delaware
United States Christiana Care Health Services - Christiana Hospital Newark Delaware
United States Christiana Care Hematology Oncology - Helen F Graham Cancer Center Newark Delaware
United States Medical Oncology Hematology Consultants, PA, Helen F. Graham Cancer Center Newark Delaware
United States Keck Hospital of USC Pasadena Pasadena California
United States Sidney Kimmel Cancer Center, Clinical Trials Organization Philadelphia Pennsylvania
United States Sidney Kimmel Cancer Center, Research Support Services Philadelphia Pennsylvania
United States Thomas Jefferson University Philadelphia Pennsylvania
United States Thomas Jefferson University - Clinical Research Institute Philadelphia Pennsylvania
United States Thomas Jefferson University Investigational Drug Services Philadelphia Pennsylvania
United States Thomas Jefferson University, Investigational Drug Service Philadelphia Pennsylvania
United States Thomas Jefferson University, Medical Oncology Philadelphia Pennsylvania
United States West Penn Hospital Pittsburgh Pennsylvania
United States Swedish Cancer Institute Seattle Washington
United States Swedish Medical Center Seattle Washington
United States Tampa General Hospital Tampa Florida
United States Tampa General Hospital Cancer Institute Tampa Florida
United States Memorial Sloan Kettering Cancer Center at Nassau Uniondale New York
United States Georgetown University Medical Center Washington District of Columbia
United States Novant Health Cancer Institute - Research Office Winston-Salem North Carolina
United States Novant Health Cancer Institute Hematology - Forsyth Winston-Salem North Carolina
United States Novant Health Forsyth Medical Center Winston-Salem North Carolina

Sponsors (1)

Lead Sponsor Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Phase 1a: Number of adverse events (AE) by severity To characterize the safety profile (incidence of AEs) Through study completion, up to 18 months
Primary Phase 1a: Number of AEs by Frequency To characterize the safety profile (incidence of AEs) and Through study completion, up to 18 months
Primary Phase 1a: Number of participants with Dose-Limiting Toxicities (DLT) To characterize the dose limiting toxicities (DLTs) of TTI-622. Up to 21-42 days
Primary Phase 1b: Number of adverse events (AE) by severity To characterize the safety profile (incidence of AEs) of TTI-622 given in combinations or as a single agent. Through study completion, up to 30 months
Primary Phase 1b: Number of adverse events (AE) by frequency To characterize the safety profile (incidence of AEs) of TTI-622 given in combination or as a single agent. Through study completion, up to 30 months
Primary Phase 1b: Number of participants with disease response To evaluate response rate of each combination treatment in the (7) combination cohorts (A1,A2, B1, B2, C1, C2, C3, D1, D2, F1, F2, F3) and for single agent treatment (Cohort E1 and E2). For AML, response = CR. For MM, response = CR+sCR+VGBR+PR. For DLBCL, OR=CR+PR Through study completion, up to 30 months
Primary Phase 1a: Maximum Tolerated Dose (MTD) To characterize the highest dose level for which no more than 1 participant in a dose cohort experienced DLTs. Baseline (the start of each sequentially increased treatment dose), up to the 3rd evaluable patient completes DLT observation period of 21 or 42 days.
Primary Phase 1b: Recommended dose of TTI-622 in combination with selected anticancer treatments To characterize the recommended dose of TTI-622 in combination with selected anticancer treatments in 5 patient populations:
TTI-622 plus azacitidine in newly diagnosed TP53-mutated AML
TTI-622 plus azacitidine and venetoclax in elderly (>/= 75 years old) or unfit, newly diagnosed TP53-wildtype AML
TTI-622 plus Carfilzomib and dexamethasone in Carfilzomib-refractory, Relapsed/Refractory (R/R) multiple myeloma (MM) after 3 or more prior lines of therapy
TTI-622 plus an anti-CD20 targeting agent (such as ruxience or rituxan) in R/R CD20+ DLBCL after 1 or more prior lines of therapy
TTI-622 plus isatuximab, carfilzomib and dexamethasone in R/R MM after 1-3 prior lines of therapy
Through study completion, up to 30 months
Primary Phase 1b: Recommended dose of TTI-622 as a single agent To characterize the recommended dose of TTI-622 as a single agent in patients with R/R MM after 3 or more prior lines of therapy. Through study completion, up to 30 months
Primary Number of participants with response assessments that show preliminary efficacy To evaluate preliminary efficacy of each combination treatment in the selected patient populations and for single-agent treatment in R/R MM Through study completion, up to 30 months
Secondary Phase 1a: TTI-622 PK parameter AUC0-t To characterize AUC0-t of TTI-622. Through study completion, up to 18 months
Secondary Phase 1a: TTI-622 PK parameter Cmax To characterize Cmax of TTI-622. Through study completion, up to 18 months
Secondary Phase 1a: Incidence of anti-drug antibodies (ADA) To characterize the immunogenicity of TTI-622. Through study completion, up to 18 months
Secondary Phase 1a: Number of participants with overall response rate (ORR) for participants treated with TTI-622. To determine the disease response. Through study completion, up to 18 months
Secondary Phase 1a: Number of participants with disease control rate (DCR) To determine the disease control rate (DCR) for participants treated with TTI-622. Through study completion, up to 18 months
Secondary Phase 1a: Time to response (TTR) To determine the time to response (TTR) for participants treated with TTI-622. Through study completion, up to 18 months
Secondary Phase 1a: Duration of Response (DR) To determine the duration of response (DR) for participants treated with TTI-622. Through study completion, up to 18 months
Secondary Phase 1a: Progression free survival (PFS) To determine the progression free survival (PFS) time for participants treated with TTI-622. Through study completion, up to 18 months
Secondary Phase 1b: TTI-622 PK parameter Cmax when combined with selected anticancer treatments or as a single agent To characterize Cmax of TTI-622 when combined with selected anticancer treatments or as a single agent. Through study completion, up to 30 months
Secondary Phase 1b: incidence of anti-drug antibodies (ADA) Immunogenicity of TTI-622 when combined with selected anticancer treatments or as a single agent To characterize the immunogenicity of TTI-622 when combined with selected anticancer treatments or as a single agent Through study completion, up to 30 months
Secondary Phase 1b: Number of participants with disease control rate (DCR) To determine the disease control rate (DCR) for participants treated with TTI-622 when combined with selected anticancer treatments or as a single agent. Through study completion, up to 30 months
Secondary Phase 1b: Time to response (TTR) To determine the time to response (TTR) for participants treated with TTI-622 when combined with selected anticancer treatments or as a single agent. Through study completion, up to 30 months
Secondary Phase 1b: Event-free survival (EFS) 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. Through study completion, up to 30 months
Secondary Phase 1b: Duration of response (DR) To determine the duration of response (DOR) for participants treated with TTI-622 when combined with selected anticancer treatments or as a single agent. Through study completion, up to 30 months
Secondary Phase 1b: Progression-free survival (PFS) 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. Through study completion, up to 30 months
Secondary Phase 1b: Number of Participants With Minimal Residual Disease Burden (MRD) Positive, Negative and Not Evaluable (NE) Status To determine minimal residual disease (MRD; for Cohorts A, B, C , E and F) for participants treated with TTI-622 when combined with selected anticancer treatments or as a single agent. Through study completion, up to 30 months
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