Ignite Creation Date:
2024-05-06 @ 8:14 PM
Last Modification Date:
2024-10-26 @ 3:23 PM
Study NCT ID:
NCT06303193
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-07-15
First Post:
2024-03-08
Brief Title:
Pacritinib a Kinase Inhibitor of CSF1R IRAK1 JAK2 and FLT3 in Adults and Pediatric Participants 12 Years of Age or Older With Myelodysplastic Syndromes or MyelodysplasticMyeloproliferative Neoplasms
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Phase III Trial of Pacritinib a Kinase Inhibitor of CSF1R IRAK1 JAK2 and FLT3 in Adults and Pediatric Participants 12 Years of Age or Older With Myelodysplastic Syndromes or MyelodysplasticMyeloproliferative Neoplasms
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-10-17
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background
Myelodysplastic syndrome MDS and myelodysplasticmyeloproliferative neoplasm MDSMPN are blood disorders that can cause serious complications in children and adults MDS and MDSMPN can also progress to acute myeloid leukemia Treatments for these disorders are risky and not always effective Better treatments are needed
Objective
To test a study drug pacritinib in adults and children with MDS or MDSMPN
Eligibility
Children aged 12 to 17 years and adults aged 18 years and older with MDS or MDSMPN
Design
Participants will be screened They will have a physical exam with blood tests They will have tests of their heart function They may have a bone marrow biopsy An area over the hip will be numbed a needle will be inserted to remove a sample of soft tissue from inside the hipbone
Pacritinib is a capsule taken by mouth All participants will take the study drug 2 times a day every day in 28-day cycles They will write down the date and time they take each capsule Doctors will assign varying dosages of the drug to different participants
Participants will have clinic visits each week during cycle 1 every 2 weeks during cycle 2 and gradually increasing to every 3 months after cycle 13 Treatment will continue for up to 8 years
Bone marrow biopsies heart tests and other tests will be repeated at intervals throughout the study Participants will also fill out questionnaires about their quality of life the symptoms of their disease and other topics
Myelodysplastic syndrome MDS and myelodysplasticmyeloproliferative neoplasm MDSMPN are blood disorders that can cause serious complications in children and adults MDS and MDSMPN can also progress to acute myeloid leukemia Treatments for these disorders are risky and not always effective Better treatments are needed
Objective
To test a study drug pacritinib in adults and children with MDS or MDSMPN
Eligibility
Children aged 12 to 17 years and adults aged 18 years and older with MDS or MDSMPN
Design
Participants will be screened They will have a physical exam with blood tests They will have tests of their heart function They may have a bone marrow biopsy An area over the hip will be numbed a needle will be inserted to remove a sample of soft tissue from inside the hipbone
Pacritinib is a capsule taken by mouth All participants will take the study drug 2 times a day every day in 28-day cycles They will write down the date and time they take each capsule Doctors will assign varying dosages of the drug to different participants
Participants will have clinic visits each week during cycle 1 every 2 weeks during cycle 2 and gradually increasing to every 3 months after cycle 13 Treatment will continue for up to 8 years
Bone marrow biopsies heart tests and other tests will be repeated at intervals throughout the study Participants will also fill out questionnaires about their quality of life the symptoms of their disease and other topics
Detailed Description:
Background
-Myelodysplastic syndromes MDS are a heterogeneous group of clonal hematopoietic disorders characterized by peripheral cytopenia ineffective and dysplastic hematopoiesis and increased risk of progression to acute myeloid leukemia AML
-The significant genetic heterogeneity of MDS contributes to the challenges in treatment
Targeting the bone marrow microenvironment BMME may allow for treatments that bypass the genetic complexity of MDS
MDS studies support a role for changes within the BMME and support the emerging concept that interdependency between the MDS clone and diverse cell populations in the BMME contributes to disease pathophysiology
CSF1R is a receptor tyrosine kinase involved in myeloid-lineage cell survival proliferation and differentiation
The presence of CSF1R-expressing cells in the AML BMME has been shown with evidence that these cells support leukemic cells through cytokine secretion and the ligand for CSF1R CSF1 has been shown to be increased in peripheral blood and bone marrow of some patients with MDS together supporting CSF1R inhibition as a plausible therapeutic target in myeloid malignancies
IRAK1 an immune modulating kinase is overexpressed and hyperactivated in patients with MDS supporting IRAK1 inhibition as a plausible therapeutic target in MDS
A small percentage of patients with MDS have activating mutations in JAK2 or FLT3 and in these patients JAK2 or FLT3 inhibition may allow for direct anti-tumor effect
Pacritinib is a multi-kinase inhibitor of CSF1R IRAK1 JAK2 and FLT3 all of which are of therapeutic interest in MDS as discussed above and has been overall well tolerated in clinical trials and has shown efficacy in the treatment of myelofibrosis
Objectives
-Phase I
To determine the safety and confirm the recommended phase II dose of pacritinib in participants who are 12-17 years of age with MDS or MDSMPN myelodysplasticmyeloproliferative neoplasms
-Phase II
To determine the efficacy of pacritinib in participants who are 18 years of age with MDS or MDSMPN as measured by overall response rate separately by risk-based cohort
Eligibility
-Participants with MDS or MDSMPN including therapy-related MDS or MDSMPN and MDS or MDSMPN with germline predisposition as defined according to the 2016 WHO criteria 2022 WHO criteria or 2022 International Consensus Classification
Age 12-17 years for phase I and age 18 years for phase II
Participants 18 years of age with higher-risk MDS HR-MDS must have resistance to hypomethylating agents as defined as failure to show improvement after at least 4 cycles of treatment primary resistance or relapse in participants with initial response to long-term treatment secondary resistance OR have intolerance to hypomethylating agents OR have a contraindication to hypomethylating agents
Participants 18 years of age with LR-MDS must be refractory to OR ineligible to receive standard of care therapies ie erythropoietin-stimulating agents lenalidomide luspatercept and present with one of the following characteristics
Severe neutropenia defined by absolute neutrophils count 05x109L without the use of granulocyte colony-stimulating factors
Symptomatic anemia defined by hemoglobin 16-week average 10 gdL and symptoms that may include fatigue weakness reduced exercise tolerance dyspnea on exertion palpitations orthostatic hypotension near syncope and restless legs
Thrombocytopenia defined as platelets 20x109L or platelets 50x109L and a history of clinically relevant non-major or major bleeding according to the ISTH classification
Participants 12-17 years of age with MDS must be relapsedrefractory OR ineligible to receive immunosuppressive therapy and hematopoietic stem cell transplantation
Ineligibility to receive hematopoietic stem cell transplantation will include participants who are not anticipated to be candidates to receive transplantation within the next 3 months due to medical comorbidities lack of appropriate donor or logistical barriers
to transplant
Participants 12-17 years of age must weigh 35 kg
Participants with MDSMPN must be relapsedrefractory failed a minimum of 1 standard of care therapy OR ineligible to receive standard of care OR without known life-prolonging therapy options OR have a diagnosis for which no known standard of care exists
Design
-This study consists of two phases which will enroll concurrently
--Phase I 3 plus 3 dose-escalation of pacritinib in participants 12-17 years of age with two planned dose levels per group Group 1 weight 35 kg to 50 kg DL1 100 mg BID DL2 200 mg BID Group 2 weight 50 kg DL1 alternating days of 100 mg
BID and 200 mg BID DL2 200 mg BID
--Phase II activity evaluation of pacritinib in participants 18 years of age separated into two cohorts
Low risk cohort Initiate on pacritinib 100 mg BID after completion of 3 cycles participants will undergo dose escalation to 200 mg BID the adult phase II recommended dose unless they meet criteria for complete remission in which case lower dose pacritinib will be continued without escalation
High risk cohort Initiate on pacritinib 200 mg BID the adult phase II recommended dose
In all participants pacritinib will be administered orally on a continuous basis for cycles of 28 days
-Myelodysplastic syndromes MDS are a heterogeneous group of clonal hematopoietic disorders characterized by peripheral cytopenia ineffective and dysplastic hematopoiesis and increased risk of progression to acute myeloid leukemia AML
-The significant genetic heterogeneity of MDS contributes to the challenges in treatment
Targeting the bone marrow microenvironment BMME may allow for treatments that bypass the genetic complexity of MDS
MDS studies support a role for changes within the BMME and support the emerging concept that interdependency between the MDS clone and diverse cell populations in the BMME contributes to disease pathophysiology
CSF1R is a receptor tyrosine kinase involved in myeloid-lineage cell survival proliferation and differentiation
The presence of CSF1R-expressing cells in the AML BMME has been shown with evidence that these cells support leukemic cells through cytokine secretion and the ligand for CSF1R CSF1 has been shown to be increased in peripheral blood and bone marrow of some patients with MDS together supporting CSF1R inhibition as a plausible therapeutic target in myeloid malignancies
IRAK1 an immune modulating kinase is overexpressed and hyperactivated in patients with MDS supporting IRAK1 inhibition as a plausible therapeutic target in MDS
A small percentage of patients with MDS have activating mutations in JAK2 or FLT3 and in these patients JAK2 or FLT3 inhibition may allow for direct anti-tumor effect
Pacritinib is a multi-kinase inhibitor of CSF1R IRAK1 JAK2 and FLT3 all of which are of therapeutic interest in MDS as discussed above and has been overall well tolerated in clinical trials and has shown efficacy in the treatment of myelofibrosis
Objectives
-Phase I
To determine the safety and confirm the recommended phase II dose of pacritinib in participants who are 12-17 years of age with MDS or MDSMPN myelodysplasticmyeloproliferative neoplasms
-Phase II
To determine the efficacy of pacritinib in participants who are 18 years of age with MDS or MDSMPN as measured by overall response rate separately by risk-based cohort
Eligibility
-Participants with MDS or MDSMPN including therapy-related MDS or MDSMPN and MDS or MDSMPN with germline predisposition as defined according to the 2016 WHO criteria 2022 WHO criteria or 2022 International Consensus Classification
Age 12-17 years for phase I and age 18 years for phase II
Participants 18 years of age with higher-risk MDS HR-MDS must have resistance to hypomethylating agents as defined as failure to show improvement after at least 4 cycles of treatment primary resistance or relapse in participants with initial response to long-term treatment secondary resistance OR have intolerance to hypomethylating agents OR have a contraindication to hypomethylating agents
Participants 18 years of age with LR-MDS must be refractory to OR ineligible to receive standard of care therapies ie erythropoietin-stimulating agents lenalidomide luspatercept and present with one of the following characteristics
Severe neutropenia defined by absolute neutrophils count 05x109L without the use of granulocyte colony-stimulating factors
Symptomatic anemia defined by hemoglobin 16-week average 10 gdL and symptoms that may include fatigue weakness reduced exercise tolerance dyspnea on exertion palpitations orthostatic hypotension near syncope and restless legs
Thrombocytopenia defined as platelets 20x109L or platelets 50x109L and a history of clinically relevant non-major or major bleeding according to the ISTH classification
Participants 12-17 years of age with MDS must be relapsedrefractory OR ineligible to receive immunosuppressive therapy and hematopoietic stem cell transplantation
Ineligibility to receive hematopoietic stem cell transplantation will include participants who are not anticipated to be candidates to receive transplantation within the next 3 months due to medical comorbidities lack of appropriate donor or logistical barriers
to transplant
Participants 12-17 years of age must weigh 35 kg
Participants with MDSMPN must be relapsedrefractory failed a minimum of 1 standard of care therapy OR ineligible to receive standard of care OR without known life-prolonging therapy options OR have a diagnosis for which no known standard of care exists
Design
-This study consists of two phases which will enroll concurrently
--Phase I 3 plus 3 dose-escalation of pacritinib in participants 12-17 years of age with two planned dose levels per group Group 1 weight 35 kg to 50 kg DL1 100 mg BID DL2 200 mg BID Group 2 weight 50 kg DL1 alternating days of 100 mg
BID and 200 mg BID DL2 200 mg BID
--Phase II activity evaluation of pacritinib in participants 18 years of age separated into two cohorts
Low risk cohort Initiate on pacritinib 100 mg BID after completion of 3 cycles participants will undergo dose escalation to 200 mg BID the adult phase II recommended dose unless they meet criteria for complete remission in which case lower dose pacritinib will be continued without escalation
High risk cohort Initiate on pacritinib 200 mg BID the adult phase II recommended dose
In all participants pacritinib will be administered orally on a continuous basis for cycles of 28 days
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 001554-C | None | None | None |