RECRUITING

Study of R289 in Patients With Lower-risk Myelodysplastic Syndromes (LR MDS)

Conditions

Low Risk Myelodysplastic Syndromes MDS LR MDS Myelodysplastic Syndromes Hematology Oncology Hem/ Onc

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

Phase 1b Study of R289 in Patients with Lower-risk Myelodysplastic Syndromes (LR MDS)

Official Title

An Open-label, Phase 1b Study of R289, an IRAK1/4 Inhibitor, in Patients With Lower-risk Myelodysplastic Syndromes (LR MDS) Who Are Relapsed/Refractory/Resistant to Prior Therapies

Quick Facts

Study Start:2022-09-12

Study Completion:2026-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05308264

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Patient must be ≥ 18 years of age at the time of signing the informed consent. * Must have definitive diagnosis of MDS with very low, low, or intermediate-1 risk (International Prognostic Scoring System (IPSS)-R ≤ 3.5) and ≤5% bone marrow myeloblasts. * Must be relapsed, refractory/resistant, intolerant, or have inadequate response to therapies with known clinical benefits for MDS, such as EPOs, luspatercept, and HMAs(i.e., azacytidine or decitabine). Patients with del (5q) must have failed prior lenalidomide therapy. * Symptomatic anemia untransfused with hemoglobin \< 9.0 g/dL and no RBC transfusion within 16 of registration or * RBC transfusion dependent defined as receiving ≥ 2 units of packed red blood cells (PRBCs) within 8 weeks in the preceding 16 weeks for a hemoglobin \<9.0 g/dL. * Exploratory Phase 1B Cohort: 1. Transfusion-dependent LR-MDS who are refractory or intolerant to, or are ineligible for ESAs. 2. No prior therapy with any approved or investigational therapies for MDS 3. No del 5q cytogenetic abnormality 4. RBC transfusion dependent defined as receiving ≥ 2 units of PRBCs within 8 weeks in the preceding 16 weeks for a hemoglobin \<9.0 g/dL * All participants must have documented marrow iron stores. If marrow iron stain is not available, the transferrin saturation must be \>20% or a serum ferritin \> 100ng/100mL * Must have Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 at screening. * Must have adequate organ function, defined as: 1. Hepatic function: * aspartate amino transferase (AST) and alanine aminotransferase (ALT) ≤ 1.5 × upper limit of normal (ULN) * total bilirubin ≤ 1.5 × ULN 2. Renal function defined as creatinine clearance \> 60 mL/min (using Cockcroft-Gault), or blood creatine \< 1.5 mg/dL	* Prior treatment for MDS (i.e., TPOs, EPOs, luspatercept, HMAs) concluded \< 4 weeks prior to study treatment * Clinically significant anemia resulting from iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis, or GI bleeding. * MDS secondary to treatment with radiotherapy, chemotherapy, and/or immunotherapy for malignant or autoimmune diseases. * Diagnosis of chronic myelomonocytic leukemia. * History of uncontrolled seizures. * Uncontrolled bacterial or viral infection (i.e., documented HIV, hepatitis B or hepatitis C). * History of an active malignancy within the past 2 years prior to study entry, with the exception of: 1. Adequately treated in situ carcinoma of the cervix uteri 2. Adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin, or 3. Low grade, early-stage prostate cancer (Gleason score 6 or below, stage 1 or 2) with no requirement for therapy at any time prior to the study, or previously resected. * History of or active, clinically significant, cardiovascular, respiratory, GI, renal, hepatic, neurological, psychiatric, musculoskeletal, genitourinary, dermatological, or other disorder that, in the Investigator's opinion, could affect the conduct of the study or the absorption, metabolism or excretion of the study treatment. * Prior history of autologous or allogeneic stem cell transplantation * Marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \> 480 milliseconds \[msec\]) (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade 1) using Fridericia's QT correction formula. * History of additional risk factors for TdP (e.g., symptomatic heart failure with left ventricular ejection fraction \[LVEF\] \<40%, hypokalemia, family history of Long QT Syndrome). * Receiving any other concurrent chemotherapy, radiotherapy, or immunotherapy (within 2 weeks of initiating study treatment), or the toxicity of the relevant prior treatment has not been resolved yet. * Use of concomitant medications that prolong the QT/QTc interval during study treatment * Use of concomitant medications that are strong CYP3A or CYP2B6 inhibitors or inducers during study treatment

Inclusion Criteria

Exclusion Criteria

* Patient must be ≥ 18 years of age at the time of signing the informed consent.
* Must have definitive diagnosis of MDS with very low, low, or intermediate-1 risk (International Prognostic Scoring System (IPSS)-R ≤ 3.5) and ≤5% bone marrow myeloblasts.
* Must be relapsed, refractory/resistant, intolerant, or have inadequate response to therapies with known clinical benefits for MDS, such as EPOs, luspatercept, and HMAs(i.e., azacytidine or decitabine). Patients with del (5q) must have failed prior lenalidomide therapy.
* Symptomatic anemia untransfused with hemoglobin \< 9.0 g/dL and no RBC transfusion within 16 of registration or
* RBC transfusion dependent defined as receiving ≥ 2 units of packed red blood cells (PRBCs) within 8 weeks in the preceding 16 weeks for a hemoglobin \<9.0 g/dL.
* Exploratory Phase 1B Cohort:
1. Transfusion-dependent LR-MDS who are refractory or intolerant to, or are ineligible for ESAs.
2. No prior therapy with any approved or investigational therapies for MDS
3. No del 5q cytogenetic abnormality
4. RBC transfusion dependent defined as receiving ≥ 2 units of PRBCs within 8 weeks in the preceding 16 weeks for a hemoglobin \<9.0 g/dL
* All participants must have documented marrow iron stores. If marrow iron stain is not available, the transferrin saturation must be \>20% or a serum ferritin \> 100ng/100mL
* Must have Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 at screening.
* Must have adequate organ function, defined as:
1. Hepatic function:
* aspartate amino transferase (AST) and alanine aminotransferase (ALT) ≤ 1.5 × upper limit of normal (ULN)
* total bilirubin ≤ 1.5 × ULN
2. Renal function defined as creatinine clearance \> 60 mL/min (using Cockcroft-Gault), or blood creatine \< 1.5 mg/dL

* Prior treatment for MDS (i.e., TPOs, EPOs, luspatercept, HMAs) concluded \< 4 weeks prior to study treatment
* Clinically significant anemia resulting from iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis, or GI bleeding.
* MDS secondary to treatment with radiotherapy, chemotherapy, and/or immunotherapy for malignant or autoimmune diseases.
* Diagnosis of chronic myelomonocytic leukemia.
* History of uncontrolled seizures.
* Uncontrolled bacterial or viral infection (i.e., documented HIV, hepatitis B or hepatitis C).
* History of an active malignancy within the past 2 years prior to study entry, with the exception of:
1. Adequately treated in situ carcinoma of the cervix uteri
2. Adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin, or
3. Low grade, early-stage prostate cancer (Gleason score 6 or below, stage 1 or 2) with no requirement for therapy at any time prior to the study, or previously resected.
* History of or active, clinically significant, cardiovascular, respiratory, GI, renal, hepatic, neurological, psychiatric, musculoskeletal, genitourinary, dermatological, or other disorder that, in the Investigator's opinion, could affect the conduct of the study or the absorption, metabolism or excretion of the study treatment.
* Prior history of autologous or allogeneic stem cell transplantation
* Marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \> 480 milliseconds \[msec\]) (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade 1) using Fridericia's QT correction formula.
* History of additional risk factors for TdP (e.g., symptomatic heart failure with left ventricular ejection fraction \[LVEF\] \<40%, hypokalemia, family history of Long QT Syndrome).
* Receiving any other concurrent chemotherapy, radiotherapy, or immunotherapy (within 2 weeks of initiating study treatment), or the toxicity of the relevant prior treatment has not been resolved yet.
* Use of concomitant medications that prolong the QT/QTc interval during study treatment
* Use of concomitant medications that are strong CYP3A or CYP2B6 inhibitors or inducers during study treatment

Contacts and Locations

Study Contact

Strait Hicklin

CONTACT

(650) 624-1100

shicklin@rigel.com

Study Locations (Sites)

University of California, Los Angeles

Los Angeles, California, 90095

United States

University of California, Irvine

Orange, California, 92868

United States

Mount Sinai Medical Center

Miami Beach, Florida, 33140

United States

University of Miami

Miami, Florida, 33136

United States

Oncology Clinical Research Referral Office

Hackensack, New Jersey, 07601

United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 09083

United States

Ichan School of Medicine at Mount Sinai

New York, New York, 10029

United States

Cleveland Clinic

Cleveland, Ohio, 44195

United States

University of Texas, Southwestern

Dallas, Texas, 75390

United States

MD Anderson Cancer Center

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: Rigel Pharmaceuticals

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-09-12

Study Completion Date2026-12

Study Record Updates

Study Start Date2022-09-12

Study Completion Date2026-12

Terms related to this study

Keywords Provided by Researchers

MDS
LR MDS
Myelodysplastic Syndromes
Hematology Oncology
Hem/ Onc

Additional Relevant MeSH Terms

Low Risk Myelodysplastic Syndromes