Acquired Pyruvate Kinase Deficiency In Clonal Myeloid Neoplasms

NCT04902833 | Active Not Recruiting

• 1 other identifier: 21-187
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This cross-sectional prevalence assessment study involves a single blood draw in specific patient populations to assess for enzymatic and genomic evidence for acquired pyruvate kinase deficiency.

Conditions

Clonal Cytopenia of Undetermined Significance; Other Clonal Myeloid Neoplasm; Unexplained Coombs-negative Non-immune Hemolytic Anemia; Pyruvate Kinase Deficiency; Myelodysplastic Syndromes; Pyruvate Kinase Deficiency Anemia; Hereditary Hemolytic Anemia; Myelodysplastic/Myeloproliferative Neoplasm; Clonal Myeloid Neoplasm; Myeloproliferative Neoplasm; Acute Myeloid Leukemia

Keywords

Pyruvate Kinase Deficiency; Pyruvate Kinase Deficiency Anemia; Hereditary Hemolytic Anemia; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasm; Clonal myeloid neoplasm; Myeloproliferative Neoplasm; Acute Myeloid Leukemia; Clonal Cytopenia of Undetermined Significance; Other clonal myeloid neoplasm; Unexplained Coombs-negative non-immune hemolytic anemia

Outcome Measures

Primary Outcomes (1)

• Overall prevalence of possible or likely acquired pyruvate kinase deficiency

  defined by PK enzyme activity or PK:HK ratio \>1 SD below the control mean (healthy subject mean) as measured by enzyme assay, or potentially pathogenic mutations in the PKLR gene as found on PKLR sequencing

  Day 1

Secondary Outcomes (7)

• Overall prevalence of definite acquired pyruvate kinase deficiency

  Day 1

• Red cell pyruvate kinase enzyme activity

  60 days

• Red cell pyruvate kinase

  60 Day

• Somatic mutations in PKLR (and other genes associated with acquired PKD) detected in the hematopoietic clone

  Day 1

• Somatic mutations in other genes associated with hemolytic anemia detected in the hematopoietic clone

  Day 1

Other Outcomes (1)

• Characterization of other possible factors involved in acquired PKD, including acquired epigenetic or gene expression factors

  Day 1

Study Arms (2)

Cohort I

Approximately 75 anemic (Hgb \<11.0 g/dL) MDS Participants without overt clinical evidence of hemolysis. \- Single Blood Draw

Procedure: Blood Draw

Cohort 2

25 Participants with clonal myeloid disorders of any type with evidence of non-immune, otherwise unexplained hemolytic anemia -Single Blood Draw

Procedure: Blood Draw

Interventions

Blood Draw PROCEDURE

Blood specimen 2-4 teaspoons

Cohort 2; Cohort I

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Cohort 1 will recruit approximately 50 anemic (Hgb \<11.0 g/dL) MDS patients without overt clinical evidence of hemolysis. Cohort 2 will recruit approximately 50 patients with clonal myeloid disorders of any type with evidence of non-immune, otherwise unexplained hemolytic anemia.

You may qualify if:

• Cohort 1
• Capable and willing to provide informed consent for participation in the study.
• Diagnosis of clonal cytopenia of undetermined significance (CCUS), myelodysplastic syndrome (MDS) or myelodysplastic/myeloproliferative neoplasm (MDS/MPN syndrome) according to 2016 World Health Organization (WHO) classification system.
• Anemia secondary to underlying clonal cytopenia of undetermined significance (CCUS), MDS or MDS/MPN syndrome, defined as a hemoglobin \<11.0 g/dL measured within 30 days of study enrollment. Anemia should not be related to nutritional deficiency (such as iron, cobalamin, folate, or copper deficiencies), peripheral immune or non-immune hemolysis, or renal disease, in the opinion of the investigator.
• Age \>18 years.
• Cohort 2
• Capable and willing to provide informed consent for participation in the study.
• Diagnosis of a clonal myeloid neoplasm, such as MDS, MDS/MPN syndrome, myeloproliferative neoplasm (MPN), acute myeloid leukemia (AML), clonal cytopenia of undetermined significance (CCUS), or other clonal myeloid neoplasm according to 2016 World Health Organization (WHO) classification system.
• A diagnosis of an otherwise unexplained Coombs-negative non-immune hemolytic anemia, according to the clinical judgement of the investigator. Some form of objective laboratory evidence must be present, including one or more of the following: negative direct antiglobulin (Coombs) test, reduced haptoglobin, elevated indirect bilirubin, elevated lactate dehydrogenase, elevated aspartate aminotransferase, or compatible findings on peripheral blood film. Results of all of these tests are not required to satisfy this criterion.
• Age \>18 years.

You may not qualify if:

• Cohort 1
• Receipt of red cell transfusion within 60 days of study enrollment.
• Cohort 2
• Have a known hereditary anemic disorder, such as thalassemia, sickle cell disease, or hereditary enzyme deficiency, with the exception of hereditary X-linked glucose-6-phosphate dehydrogenase deficiency known not to cause chronic baseline hemolysis. Testing for these diagnoses is not required unless deemed clinically necessary.
• Have a known untreated nutritional anemia or acquired disorder resulting in hemolysis, such as paroxysmal nocturnal hemoglobinuria (PNH).

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Agios Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Pyruvate Kinase Deficiency of Red Cells; Anemia, Hemolytic, Congenital; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Myeloproliferative Disorders; Leukemia, Myeloid, Acute

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Bone Marrow Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Hanny Al-Samkari, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 21, 2021
• First Posted: May 26, 2021
• Study Start: February 1, 2022
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 25, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (1)