Brief Summary
This is a Phase 1 cohort, dose-escalation, dose-expansion study of PRT543 in patients with advanced cancers who have exhausted available treatment options. The purpose of this study is to define a safe dose and schedule to be used in subsequent development of PRT543.
Brief Title
A Study of PRT543 in Participants With Advanced Solid Tumors and Hematologic Malignancies
Detailed Description
This is a multicenter, open-label, sequential-cohort, dose-escalation, dose-expansion Phase 1 study of PRT543 in patients with advanced cancers who have exhausted available treatment options. Enrollment will take place concurrently into two distinct patient groups (one for solid tumors/lymphomas and one for hematological malignancies). The study will consist of 2 parts, a dose escalation part, and once the recommended phase 2 dose (RP2D) has been determined, a cohort expansion part involving up to ten separate cohorts. For patients, the study will include a screening phase, a treatment phase, and a post treatment follow-up phase. An end-of-study visit will be conducted within 30 days after the last dose of PRT543.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Relapsed/Refractory Advanced Solid Tumors
Relapsed/Refractory Diffuse Large B-cell Lymphoma
Relapsed/Refractory Myelodysplasia
Relapsed/Refractory Myelofibrosis
Adenoid Cystic Carcinoma
Relapsed/Refractory Mantle Cell Lymphoma
Relapsed/Refractory Acute Myeloid Leukemia
Refractory Chronic Myelomonocytic Leukemia
Eligibility Criteria
Inclusion Criteria:
* Metastatic or advanced solid tumor; or advanced diffuse large B-cell lymphoma; or advanced mantle cell lymphoma; or relapsed myelodysplastic syndrome, acute myeloid leukemia or chronic myelomonocytic leukemia; or relapsed myelofibrosis. All malignancies must be refractory to established therapies
* Biomarker-selected solid tumors
* Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1
* Adequate organ function (bone marrow, hepatic, renal, cardiovascular)
* Female patients of childbearing potential must have a negative pregnancy test within 7 days of the start of treatment and must agree to use an effective method of contraception during the trial
Exclusion Criteria:
* Primary malignancies of the Central Nervous System(CNS) or uncontrolled CNS metastases
* Requirement of pharmacologic doses of glucocorticoids
* Prior treatment with chimeric antigen receptor T cells (CAR-T cells)
* HIV positive; known active hepatitis B or C
* Known hypersensitivity to any of the components of PRT543
* Prior allogeneic bone marrow transplant; autologous hematopoietic transplantation less than 100 days since transplantation
* Metastatic or advanced solid tumor; or advanced diffuse large B-cell lymphoma; or advanced mantle cell lymphoma; or relapsed myelodysplastic syndrome, acute myeloid leukemia or chronic myelomonocytic leukemia; or relapsed myelofibrosis. All malignancies must be refractory to established therapies
* Biomarker-selected solid tumors
* Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1
* Adequate organ function (bone marrow, hepatic, renal, cardiovascular)
* Female patients of childbearing potential must have a negative pregnancy test within 7 days of the start of treatment and must agree to use an effective method of contraception during the trial
Exclusion Criteria:
* Primary malignancies of the Central Nervous System(CNS) or uncontrolled CNS metastases
* Requirement of pharmacologic doses of glucocorticoids
* Prior treatment with chimeric antigen receptor T cells (CAR-T cells)
* HIV positive; known active hepatitis B or C
* Known hypersensitivity to any of the components of PRT543
* Prior allogeneic bone marrow transplant; autologous hematopoietic transplantation less than 100 days since transplantation
Inclusion Criteria
Inclusion Criteria:
* Metastatic or advanced solid tumor; or advanced diffuse large B-cell lymphoma; or advanced mantle cell lymphoma; or relapsed myelodysplastic syndrome, acute myeloid leukemia or chronic myelomonocytic leukemia; or relapsed myelofibrosis. All malignancies must be refractory to established therapies
* Biomarker-selected solid tumors
* Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1
* Adequate organ function (bone marrow, hepatic, renal, cardiovascular)
* Female patients of childbearing potential must have a negative pregnancy test within 7 days of the start of treatment and must agree to use an effective method of contraception during the trial
* Metastatic or advanced solid tumor; or advanced diffuse large B-cell lymphoma; or advanced mantle cell lymphoma; or relapsed myelodysplastic syndrome, acute myeloid leukemia or chronic myelomonocytic leukemia; or relapsed myelofibrosis. All malignancies must be refractory to established therapies
* Biomarker-selected solid tumors
* Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1
* Adequate organ function (bone marrow, hepatic, renal, cardiovascular)
* Female patients of childbearing potential must have a negative pregnancy test within 7 days of the start of treatment and must agree to use an effective method of contraception during the trial
Gender
All
Gender Based
false
Keywords
PRMT5
PRMT5 Inhibitor
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT03886831
Org Class
Industry
Org Full Name
Prelude Therapeutics
Org Study Id
PRT543-01
Overall Status
Completed
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 1, Open-Label, Multicenter, Dose Escalation, Dose Expansion Study of PRT543 in Patients With Advanced Solid Tumors and Hematologic Malignancies
Primary Outcomes
Outcome Description
Dose limiting toxicities (DLTs) will be evaluated during the first cycle
Outcome Measure
To describe dose limiting toxicities (DLT) of PRT543
Outcome Time Frame
Baseline through Day 28.
Outcome Description
The maximum tolerated dose (MTD) will be established for further investigation in participants with advanced malignancies who have failed prior treatments.
Outcome Measure
To determine the maximally tolerated dose (MTD)
Outcome Time Frame
Baseline through approximately 2 years.
Outcome Description
The recommended phase 2 dose (RP2D) and optimal dosing schedule of PRT543 will be established for further investigation in participants with advanced malignancies who have failed prior treatments.
Outcome Measure
To determine the recommended phase 2 dose (RP2D) and schedule of PRT543
Outcome Time Frame
Baseline through approximately 2 years.
Secondary Outcomes
Outcome Description
Adverse events as characterized by type, frequency, severity, timing, seriousness and relationship to study therapy
Outcome Time Frame
Baseline through approximately 2 years
Outcome Measure
To describe the adverse event profile and tolerability of PRT543
Outcome Description
PRT543 pharmacokinetics will be calculated including the maximum observed plasma concentration.
Outcome Time Frame
Cycle 1 (each cycle is 28 days) on Days 1, 15, and/or 25: predose and 0.5, 1, 2, 4, 8, 24 hours postdose; predose on Cycle 1, Days 3, 4, 8, 11, and/or 22. Subsequently for Cycle 2 and beyond (until end of study treatment) on Day 1.
Outcome Measure
To determine the maximum observed plasma concentration (Cmax) of PRT543
Outcome Description
PRT543 pharmacokinetics will be calculated including the time to reach maximum observed plasma concentration
Outcome Time Frame
Cycle 1 (each cycle is 28 days) on Days 1, 15, and/or 25: predose and 0.5, 1, 2, 4, 8, 24 hours postdose; predose on Cycle 1, Days 3, 4, 8, 11, and/or 22. Subsequently for Cycle 2 and beyond (until end of study treatment) on Day 1.
Outcome Measure
To determine the time to reach maximum observed plasma concentration (Tmax) of PRT543
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Ana Acuna-Villaorduna
Investigator Email
aacunavi@montefiore.org
Investigator Phone
Categories Mesh Debug
Blood & Bone Marrow Cancers --- LEUKEMIA, MYELOID, ACUTE
Cancer --- NEOPLASMS
Blood & Bone Marrow Cancers --- LYMPHOPROLIFERATIVE DISORDERS
Blood & Bone Marrow Cancers --- LYMPHATIC DISEASES
Blood & Bone Marrow Cancers --- IMMUNOPROLIFERATIVE DISORDERS
Infectious Disease --- IMMUNE SYSTEM DISEASES
Lung --- IMMUNE SYSTEM DISEASES
Blood Disorders --- ANEMIA
Blood & Bone Marrow Cancers --- ANEMIA
Blood Disorders --- HEMATOLOGIC DISEASES
Blood & Bone Marrow Cancers --- HEMATOLOGIC DISEASES
Blood & Bone Marrow Cancers --- MYELODYSPLASTIC SYNDROMES
Blood & Bone Marrow Cancers --- BONE MARROW DISEASES
Blood & Bone Marrow Cancers --- MYELOPROLIFERATIVE DISORDERS
Endocrine System Cancers --- ADENOCARCINOMA
Cancer --- CARCINOMA
Lung & Chest Cancers --- NEOPLASMS, GLANDULAR AND EPITHELIAL
Blood & Bone Marrow Cancers --- LEUKEMIA, MYELOID
Cancer --- LEUKEMIA
Blood & Bone Marrow Cancers --- LEUKEMIA
Blood & Bone Marrow Cancers --- MYELODYSPLASTIC-MYELOPROLIFERATIVE DISEASES
MeSH Terms
RECURRENCE
LYMPHOMA, LARGE B-CELL, DIFFUSE
ANEMIA, REFRACTORY, WITH EXCESS OF BLASTS
PRIMARY MYELOFIBROSIS
CARCINOMA, ADENOID CYSTIC
LYMPHOMA, MANTLE-CELL
LEUKEMIA, MYELOID, ACUTE
LEUKEMIA, MYELOMONOCYTIC, CHRONIC
DISEASE ATTRIBUTES
PATHOLOGIC PROCESSES
PATHOLOGICAL CONDITIONS, SIGNS AND SYMPTOMS
LYMPHOMA, B-CELL
LYMPHOMA, NON-HODGKIN
LYMPHOMA
NEOPLASMS BY HISTOLOGIC TYPE
NEOPLASMS
LYMPHOPROLIFERATIVE DISORDERS
LYMPHATIC DISEASES
HEMIC AND LYMPHATIC DISEASES
IMMUNOPROLIFERATIVE DISORDERS
IMMUNE SYSTEM DISEASES
ANEMIA, REFRACTORY
ANEMIA
HEMATOLOGIC DISEASES
MYELODYSPLASTIC SYNDROMES
BONE MARROW DISEASES
MYELOPROLIFERATIVE DISORDERS
ADENOCARCINOMA
CARCINOMA
NEOPLASMS, GLANDULAR AND EPITHELIAL
LEUKEMIA, MYELOID
LEUKEMIA
MYELODYSPLASTIC-MYELOPROLIFERATIVE DISEASES
CHRONIC DISEASE