Clinical trial NCT03530683: A Clinical Trial to Learn About the Study Medicine Called Maplirpacept (PF-07901801), Alone and When Used in Combination With Other Medicines to Treat Participants With Advanced Hematological Malignancies, Including Lymphoma, Leukemia and Multiple Myeloma
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Lymphoma
Multiple Myeloma
Acute Myeloid Leukemia
Diffuse Large B-Cell Lymphoma
Keywords: Neoplasms
Lymphoma
Myeloma
Leukemia
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2018-05-21
Enrollment: 189
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility 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, 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.

Primary outcomes:
measure: Phase 1a: Number of adverse events (AE) by severity
timeFrame: Through study completion, up to 18 months
measure: Phase 1a: Number of AEs by Frequency
timeFrame: Through study completion, up to 18 months
measure: Phase 1a: Number of participants with Dose-Limiting Toxicities (DLT)
timeFrame: Up to 21-42 days
measure: Phase 1b: Number of adverse events (AE) by severity
timeFrame: Through study completion, up to 30 months
measure: Phase 1b: Number of adverse events (AE) by frequency
timeFrame: Through study completion, up to 30 months
measure: Phase 1b: Number of participants with disease response
timeFrame: Through study completion, up to 30 months
measure: Phase 1a: Maximum Tolerated Dose (MTD)
timeFrame: Baseline (the start of each sequentially increased treatment dose), up to the 3rd evaluable patient completes DLT observation period of 21 or 42 days.
measure: Phase 1b: Recommended dose of TTI-622 in combination with selected anticancer treatments
timeFrame: Through study completion, up to 30 months
measure: Phase 1b: Recommended dose of TTI-622 as a single agent
timeFrame: Through study completion, up to 30 months
measure: Number of participants with response assessments that show preliminary efficacy
timeFrame: Through study completion, up to 30 months
Secondary outcomes:
measure: Phase 1a: TTI-622 PK parameter AUC0-t
timeFrame: Through study completion, up to 18 months
measure: Phase 1a: TTI-622 PK parameter Cmax
timeFrame: Through study completion, up to 18 months
measure: Phase 1a: Incidence of anti-drug antibodies (ADA)
timeFrame: Through study completion, up to 18 months
measure: Phase 1a: Number of participants with overall response rate (ORR) for participants treated with TTI-622.
timeFrame: Through study completion, up to 18 months
measure: Phase 1a: Number of participants with disease control rate (DCR)
timeFrame: Through study completion, up to 18 months
measure: Phase 1a: Time to response (TTR)
timeFrame: Through study completion, up to 18 months
measure: Phase 1a: Duration of Response (DR)
timeFrame: Through study completion, up to 18 months
measure: Phase 1a: Progression free survival (PFS)
timeFrame: Through study completion, up to 18 months
measure: Phase 1b: TTI-622 PK parameter Cmax when combined with selected anticancer treatments or as a single agent
timeFrame: Through study completion, up to 30 months
measure: Phase 1b: incidence of anti-drug antibodies (ADA) Immunogenicity of TTI-622 when combined with selected anticancer treatments or as a single agent
timeFrame: Through study completion, up to 30 months
measure: Phase 1b: Number of participants with disease control rate (DCR)
timeFrame: Through study completion, up to 30 months
measure: Phase 1b: Time to response (TTR)
timeFrame: Through study completion, up to 30 months
measure: Phase 1b: Event-free survival (EFS)
timeFrame: Through study completion, up to 30 months
measure: Phase 1b: Duration of response (DR)
timeFrame: Through study completion, up to 30 months
measure: Phase 1b: Progression-free survival (PFS)
timeFrame: Through study completion, up to 30 months
measure: Phase 1b: Number of Participants With Minimal Residual Disease Burden (MRD) Positive, Negative and Not Evaluable (NE) Status
timeFrame: Through study completion, up to 30 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Keck Hospital of USC
state: California
city: Los Angeles
country: United States
facility: LAC+USC Medical Center
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: Pasadena
country: United States
facility: Keck Hospital of USC Pasadena
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Denver
country: United States
facility: HealthONE Presbyterian/St. Luke's Medical Center
state: Colorado
city: Newark
country: United States
facility: Christiana Care Health Services
state: Delaware
city: Newark
country: United States
facility: Christiana Care Hematology Oncology - Helen F Graham Cancer Center
state: Delaware
city: Newark
country: United States
facility: Medical Oncology Hematology Consultants, PA, Helen F. Graham Cancer Center
state: Delaware
city: Newark
country: United States
facility: Christiana Care Health Services - Christiana Hospital
state: Delaware
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Tampa
country: United States
facility: Tampa General Hospital Cancer Institute
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Atlanta
country: United States
facility: Blood and Marrow Transplant Group of Georgia
state: Georgia
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Indianapolis
country: United States
facility: Indiana Blood & Marrow Transplantation
state: Indiana
city: Indianapolis
country: United States
facility: Indiana Blood and Marrow Transplantation-Administrative Offices
state: Indiana
city: Indianapolis
country: United States
facility: Indiana Blood and Marrow Transplantation-Clinic
state: Indiana
city: Louisville
country: United States
facility: Norton Cancer Institute, St Matthews Campus
state: Kentucky
city: Louisville
country: United States
facility: Norton Cancer Institute, St. Matthews Campus, Attn. Becky Champion, PharmD
state: Kentucky
city: Louisville
country: United States
facility: Norton Diagnostic Center-Dupont (PET Scans)
state: Kentucky
city: Louisville
country: United States
facility: Norton Women & Children's Hospital
state: Kentucky
city: Ann Arbor
country: United States
facility: University of Michigan Hospitals
state: Michigan
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Farmington Hills
country: United States
facility: Karmanos Cancer Institute Weisberg Cancer Treatment Center
state: Michigan
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Cancer Center at Basking Ridge
state: New Jersey
city: Florham Park
country: United States
facility: Summit Medical Group Cancer Center
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Cancer Center at Monmouth
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Cancer Center at Montvale
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Commack
country: United States
facility: Memorial Sloan Kettering Cancer Center at Commack
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Cancer Center at Westchester
state: New York
city: Long Island City
country: United States
facility: Memorial Sloan Kettering Cancer Center - Investigational Drug Service Pharmacy
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center - David H. Koch Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center (Outpatient Center)
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering Cancer Center at Nassau
state: New York
city: Charlotte
country: United States
facility: Novant Health Cancer Institute - Research Office
state: North Carolina
city: Charlotte
country: United States
facility: Novant Health Cancer Institute Hematology - Charlotte
state: North Carolina
city: Charlotte
country: United States
facility: Novant Health Presbyterian Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Novant Health Cancer Institute - Research Office
state: North Carolina
city: Winston-Salem
country: United States
facility: Novant Health Cancer Institute Hematology - Forsyth
state: North Carolina
city: Winston-Salem
country: United States
facility: Novant Health Forsyth Medical Center
state: North Carolina
city: Canton
country: United States
facility: Gabrail Cancer Center Research
state: Ohio
city: Philadelphia
country: United States
facility: Sidney Kimmel Cancer Center, Clinical Trials Organization
state: Pennsylvania
city: Philadelphia
country: United States
facility: Sidney Kimmel Cancer Center, Research Support Services
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University - Clinical Research Institute
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Investigational Drug Services
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University, Investigational Drug Service
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University, Medical Oncology
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: West Penn Hospital
state: Pennsylvania
city: Greenville
country: United States
facility: Prisma Health, Institute for Translational Oncology Research, Clinical Research Unit
state: South Carolina
city: Greenville
country: United States
facility: Prisma Health-Upstate Cancer Institute
state: South Carolina
city: Knoxville
country: United States
facility: University of TN Medical Center
state: Tennessee
city: Houston
country: United States
facility: Oncology Consultants P.A.
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: