Pyruvate Kinase DeficiencyNCT04902833
Acquired Pyruvate Kinase Deficiency In Clonal Myeloid Neoplasms
An observational study of Pyruvate Kinase Deficiency and Pyruvate Kinase Deficiency Anemia, run by Massachusetts General Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pyruvate Kinase Deficiency, Pyruvate Kinase Deficiency Anemia, Hereditary Hemolytic Anemia
- What is being tested?
- Blood Draw
- Type of treatment
- Surgery or procedure
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2022to 1 Feb 2026
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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
Show all 10Show fewer
- 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.
Who cannot join
- Cohort 1
- Receipt of red cell transfusion within 60 days of study enrollment.
- Have a known untreated nutritional anemia or acquired disorder resulting in hemolysis, such as paroxysmal nocturnal hemoglobinuria (PNH). A known hereditary anemia (such as thalassemia trait) is not exclusionary if the patient's baseline hemoglobin has worsened significantly (in the opinion of the investigator) after development and diagnosis of MDS.
- 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).
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02115
About this study
Official title: Characterization Of Acquired Pyruvate Kinase Deficiency In Clonal Myeloid Neoplasms
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.
Read the detailed description
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.
- Red cell pyruvate kinase enzyme activity and next-generation sequencing (NGS) hereditary hemolytic anemia panels will be performed on samples from all recruited participants.
- The study will recruit patients to two separate cohorts.
- Cohort 1 will recruit approximately 75 anemic (Hgb <11.0 g/dL) MDS participants without overt clinical evidence of hemolysis.
- Cohort 2 will recruit approximately 25 participants with clonal myeloid disorders of any type with evidence of non-immune, otherwise unexplained hemolytic anemia
- Participation in the study involves a single blood draw. Basic information about the participant's blood disorder will also be collected.
It is expected that about 100 people will take part in this research study
- Conditions
- Pyruvate Kinase Deficiency, Pyruvate Kinase Deficiency Anemia, Hereditary Hemolytic Anemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasm, Clonal Myeloid Neoplasm
- Being tested
- Blood Draw
- 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
- Medical subject headings
- Pyruvate Kinase Deficiency of Red Cells, Anemia, Hemolytic, Congenital, Myelodysplastic Syndromes, Myelodysplastic-Myeloproliferative Diseases, Myeloproliferative Disorders, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood DrawProcedure or surgery
Blood specimen 2-4 teaspoons
| Study group | Role | What they receive |
|---|---|---|
| Cohort I | Approximately 75 anemic (Hgb <11.0 g/dL) MDS Participants without overt clinical evidence of hemolysis.
- Single Blood Draw Receives: 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 Receives: Procedure: Blood Draw |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Day 1
Secondary outcomes (7)
Overall prevalence of definite acquired pyruvate kinase deficiency
Defined by PK enzyme activity below normal (or a PK:HK ratio <8.7) as measured by enzyme assay, or known pathogenic mutations in the PKLR gene as found on PKLR sequencing
Measured: Day 1
Red cell pyruvate kinase enzyme activity
Red cell pyruvate kinase enzyme activity in patients not receiving red cell transfusion in the 60 days prior to blood draw
Measured: 60 days
Red cell pyruvate kinase
hexokinase enzyme activity ratio in patients not receiving red cell transfusion in the 60 days prior to blood draw
Measured: 60 Day
Somatic mutations in PKLR (and other genes associated with acquired PKD) detected in the hematopoietic clone
Measured: Day 1
Somatic mutations in other genes associated with hemolytic anemia detected in the hematopoietic clone
Measured: Day 1
Characterization of pyruvate kinase-related red cell metabolites (ATP, 2,3-DPG) and pyruvate kinase-R protein in patients with clonal myeloid disorders
Measured: Day 1
Impact of pyruvate kinase activators on PK activity in vitro
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2021
- Study start1 Feb 2022
- Primary completion1 Feb 2026
- Study completion1 Feb 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pyruvate Kinase DeficiencyStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Agios Pharmaceuticals, Inc.
- Responsible party
- Principal investigator, Hanny Al-Samkari, MD, Massachusetts General Hospital
- Investigators
- Hanny Al-Samkari, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04902833
- Sponsor's protocol ID
- 21-187
- Status last verified
- May 2026
- First submitted
- 21 May 2021
- Last updated
- 19 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterization Of Acquired Pyruvate Kinase Deficiency In Clonal Myeloid Neoplasms
- ClinicalTrials.gov ID
- NCT04902833
- Acronym / sponsor ID
- 21-187
- Conditions
- Pyruvate Kinase Deficiency, Pyruvate Kinase Deficiency Anemia, Hereditary Hemolytic Anemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasm, Clonal Myeloid Neoplasm
- Keywords
- Pyruvate Kinase Deficiency, Pyruvate Kinase Deficiency Anemia, Hereditary Hemolytic Anemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasm, Clonal myeloid neoplasm, Myeloproliferative Neoplasm, Acute Myeloid Leukemia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Agios Pharmaceuticals, Inc.
- Study start
- 1 Feb 2022 (actual)
- Primary completion
- 1 Feb 2026 (actual)
- Study completion
- 1 Feb 2026 (actual)
- First posted
- 26 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
- Red cell pyruvate kinase enzyme activity and next-generation sequencing (NGS) hereditary hemolytic anemia panels will be performed on samples from all recruited participants.
- The study will recruit patients to two separate cohorts.
- Cohort 1 will recruit approximately 75 anemic (Hgb <11.0 g/dL) MDS participants without overt clinical evidence of hemolysis.
- Cohort 2 will recruit approximately 25 participants with clonal myeloid disorders of any type with evidence of non-immune, otherwise unexplained hemolytic anemia
- Participation in the study involves a single blood draw. Basic information about the participant's blood disorder will also be collected.
It is expected that about 100 people will take part in this research study
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort I | – | Procedure: Blood DrawApproximately 75 anemic (Hgb <11.0 g/dL) MDS Participants without overt clinical evidence of hemolysis. - Single Blood Draw |
| Cohort 2 | – | Procedure: Blood Draw25 Participants with clonal myeloid disorders of any type with evidence of non-immune, otherwise unexplained hemolytic anemia -Single Blood Draw |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (10 listed)
- Cohort 1
- Cohort 2
Key exclusion criteria (6 listed)
- Cohort 1
- Cohort 2
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood DrawBlood specimen 2-4 teaspoons | Procedure or surgery | Cohort 2, Cohort I |
Primary outcome
Overall prevalence of possible or likely acquired pyruvate kinase deficiency
Time frame: Day 1
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
7 secondary outcomes
Overall prevalence of definite acquired pyruvate kinase deficiency
Time frame: Day 1
Red cell pyruvate kinase enzyme activity
Time frame: 60 days
Red cell pyruvate kinase
Time frame: 60 Day
Somatic mutations in PKLR (and other genes associated with acquired PKD) detected in the hematopoietic clone
Time frame: Day 1
Somatic mutations in other genes associated with hemolytic anemia detected in the hematopoietic clone
Time frame: Day 1
Characterization of pyruvate kinase-related red cell metabolites (ATP, 2,3-DPG) and pyruvate kinase-R protein in patients with clonal myeloid disorders
Time frame: Day 1
Impact of pyruvate kinase activators on PK activity in vitro
Time frame: Day 1
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2026.
- Individual participant dataSharing planned: Yes. The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
Related trials for Pyruvate Kinase Deficiency
Enrolling by invitationPhase 4
A Study to Provide Access to Mitapivat for Participants Who Previously Participated in an Agios-Sponsored Mitapivat Study
Pyruvate Kinase Deficiency, Anemia, Hemolytic
Active, not recruitingObservational study
Pyruvate Kinase Deficiency Global Longitudinal Registry
Pyruvate Kinase Deficiency
Active, not recruitingPhase 3
A Study to Evaluate the Efficacy and Safety of Mitapivat in Pediatric Participants With Pyruvate Kinase Deficiency (PKD) Who Are Regularly Transfused, Followed by a 5-Year Extension Period
Pediatric Pyruvate Kinase Deficiency, Pediatric Hemolytic Anemia
Active, not recruitingPhase 3
A Study to Evaluate the Efficacy and Safety of Mitapivat in Pediatric Participants With Pyruvate Kinase Deficiency (PKD) Who Are Not Regularly Transfused, Followed by a 5-Year Extension Period
Pediatric Pyruvate Kinase Deficiency, Pediatric Hemolytic Anemia
Not yet recruitingPhase 1
High-Dose Vitamin C in G6PDA and Pyruvate Kinase Deficiency: A Safety Study
Pyruvate Kinase Deficiency, Glucose 6 Phosphate Dehydrogenase Deficiency
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hanny Al-Samkari, MD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pyruvate Kinase Deficiency and Pyruvate Kinase Deficiency Anemia, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall prevalence of possible or likely acquired pyruvate kinase deficiency (time frame: Day 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2026.