Symptoms and General Pathology

All Conditions

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Urinary Tract, Sexual Organs, and Pregnancy Conditions

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Myelodysplastic Syndromes

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Hemoglobinuria, Paroxysmal

Bone Marrow Diseases

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Leukocyte Disorders

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Anemia, Hemolytic

Infant, Newborn, Diseases

Genetic Diseases, Inborn

Participants may undergo blood sample collection, a bone marrow biopsy, a skin punch biopsy, hair follicle collection, a buccal swab, and/or saliva collection for NGS analysis on study. Patients may additionally undergo clinical assessment and may receive genetic counseling on study.

Undergo blood sample, hair follicle, and saliva collection

Biospecimen Collection

Bone Marrow Biopsy

Punch Biopsy

Buccal Swab

Clinical Evaluation

Genetic Counseling

Quality-of-Life Assessment

Electronic Health Record Review

Brittany Burnap

Clinical Trials Referral Office

Cecilia Y. Arana Yi, M.D.

James M. Foran, M.D.

Mrinal S. Patnaik, MBBS

This clinical trial tests next generation sequencing (NGS) for the detection of precursor features of pre-myeloid cancers and bone marrow failure syndromes. NGS is a procedure that looks at relevant cancer associated genes and what they do. Finding genetic markers for pre-malignant conditions may help identify patients who are at risk of pre-myeloid cancers and bone marrow failure syndromes and lead to earlier intervention.

PRIMARY OBJECTIVES:

I. To use genomics and functional translational studies to diagnose, prognosticate and potentially offer therapeutic directives for patients with precursor features of myeloid neoplasms (myelodysplastic syndrome \[MDS\], myeloproliferative neoplasms \[MPN\], MDS/MPN overlap syndrome) and germline predisposition/bone marrow failure states, who do not meet the criteria for the diagnosis of these cancers as of yet.

II. To identify patients with precursor myeloid malignancies and bone marrow failure syndromes.

III. To examine the utility of NGS methods for discovery of targets or pathways involved in precursor features of myeloid cancer and bone marrow failure.

IV. To use clinomics/genomics to better understand pathobiology and risk of disease progression.

V. To help better understand the implications of variants of unknown significance using computational biology and functional studies.

VI. To utilize normal, age and sex matched controls to validate genetic and epigenetic testing carried out under this protocol (essential for accurate data analysis).

VII. To assess frailty in patients with clonal hematopoiesis in order to validate genetic and epigenetic testing completed under this protocol as objective assessments of frailty and aging in comparison to standard of care frailty and geriatric assessments.

OUTLINE:

Participants may undergo blood sample collection, a bone marrow biopsy, a skin punch biopsy, hair follicle collection, a buccal swab, and/or saliva collection for NGS analysis on study. Patients may additionally undergo clinical assessment and may receive genetic counseling on study.

Pre-myeloid Cancer and Bone Marrow Failure Clinic Study

Assessed by the number of subjects whose cytopenias are persistent or progressive over the course of the study

Assessed by the number of subjects who have evolved to MDS over the course of the study

Assessed by the number of subjects who have evolved to AML over the course of the study

Mayo Clinic

Principal Investigator

Thalassemia

beta-Thalassemia

Precancerous Conditions

Anemia, Hemolytic, Congenital

Hemoglobinopathies

Beta-thalassemia

SLN124

Placebo

This study will investigate the safety and tolerability of SLN124 in patients with Thalassaemia or patients with Very Low- and Low-risk Myelodysplastic Syndrome (MDS) after single ascending s.c. doses and multiple doses in healthy male and female subjects. Up to 7 cohorts of 56 patients with Thalassaemia and up to 7 cohorts of 56 patients with MDS will be enrolled. Each subject will receive single or multiple doses of SLN124 or placebo given by subcutaneous (s.c) injection.

A Study Investigate the Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Response of SLN124 in Adults With Alpha/Beta-thalassaemia and Very Low- and Low-risk Myelodysplastic Syndrome

A Randomised, Single-blind, Placebo-controlled, Phase 1, Single-ascending and Multiple-dose Study in Adult Subjects With Alpha/Beta-thalassaemia and Very Low- and Low-risk Myelodysplastic Syndrome to Investigate the Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Response of SLN124.

safety and tolerability will be reported separately following single-dose administration.

safety and tolerability will be reported separately following multi-dose administration.

Will be reported separately following single-dose and multiple-dose administration.

safety and tolerability will be reported separately following single-dose and multiple-dose administration.

Silence Therapeutics plc

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

All Drugs and Chemicals

Chrysarobin

Fixed starting doses (different doses for lower body weight \& higher body weight) of FG-4592 administered orally 3 times a week (TIW) for up to 26 weeks; dose adjustments to Hb levels are allowed during the study.

Fixed starting doses (different doses for lower body weight \& higher body weight) of FG-4592 administered orally TIW for up to 26 weeks; dose adjustments to Hb levels are allowed during the study.

Placebo (matching to FG-4592) administered orally TIW for up to 26 weeks.

FG-4592

The objective of this study to evaluate the efficacy FG-4592 for the treatment of anemia in Chinese participants with lower risk MDS.

This is a Phase 2/3 trial with sequential Phase 2 and Phase 3 components. In each part, there is an up to 4 weeks screening period followed by a treatment period of 26 weeks and a 4 week follow-up period.

Phase 2 part is an open label, single arm, dose-escalation study. Phase 3 component is a randomized, double blind, placebo-controlled study.

Efficacy and Safety of FG-4592 for Treatment of Anemia in Participants With Lower Risk Myelodysplastic Syndrome (MDS)

A Phase 2/3 Trial of FG-4592 for Treatment of Anemia in Subjects With Lower Risk Myelodysplastic Syndrome

Hemoglobin response to FG-4592 is defined as an increase in mean Hb of ≥1.0 grams (g)/deciliter (dL) from baseline within any 8-week period during the study without transfusion.

Hb response to FG-4592 is defined as an increase in mean Hb of ≥1.0 g/dL from baseline within any 8-week period during the study without transfusion.

AstraZeneca

FibroGen

Antineoplastic Agents

Lenalidomide

750 μg AMG 531 weekly by subcutaneous injection + lenalidomide (10 mg orally per day) for 16 weeks (Part A)

Placebo weekly via subcutaneous injection + lenalidomide (10 mg orally per day) for 16 weeks (Part B)

Placebo weekly via subcutaneous injection + lenalidomide (10 mg orally per day) for 16 weeks (Part A)

500 μg AMG 531 weekly by subcutaneous injection + lenalidomide (10 mg orally per day) for 16 weeks (Part A)

750 μg AMG 531 biweekly by subcutaneous injection + lenalidomide (10 mg orally per day) for 16 weeks (Part B)

AMG 531 will be administered by subcutaneous injection at a dose of 500 or 750 μg.

AMG 531

Subjects in the control group will receive placebo via subcutaneous injection.

This is a dose and schedule finding study of AMG 531 designed to assess the activity of AMG 531 to reduce the rate of clinically significant bleeding and blood transfusions in subjects with myelodysplastic syndrome (MDS) receiving lenalidomide. Subjects with MDS that are planned to receive at least four cycles of lenalidomide for treatment of their disease are appropriate to screen for this study.

All subjects meeting the eligibility criteria will receive lenalidomide 10 mg capsule by mouth daily every day of each 28-day cycle. Subjects will receive AMG 531 or placebo once a week by subcutaneous injection for 16 weeks.

A Safety and Efficacy Study to Evaluate AMG 531 Treatment in Subject With Myelodysplastic Syndrome Receiving Revlimid

A Randomized, Double Blind, Placebo Controlled Study Evaluating the Efficacy and Safety of AMG 531 Treatment of Subjects With Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS) Receiving Lenalidomide.

Occurrence of one or more clinically significant thrombocytopenic events, defined as either Common Terminology Criteria for Adverse Events (CTCAE) v. 3 grade 3 or 4 thrombocytopenia starting from week 3 of cycle 1 or receipt of platelet transfusions starting from week 1 of cycle 1 and continuing through the end of treatment visit.

Occurrence of lenalidomide dose reduction and delay due to thrombocytopenia

CR = decrease in bone marrow blast (≤5%) and improvement in peripheral blood counts (Hgb ≥ 11 g/dL, platelets ≥ 100x10\^9/L, neutrophils ≥ 1x10\^9/L, peripheral blasts=0%). PR = improvement in peripheral blood counts plus a decrease in bone marrow blasts ≥50% but not ≤5, or decrease in International Prognostic Scoring System score.

Occurrence of one or more platelet transfusions during the treatment period

Amgen

Global Development Leader

The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.

Two subjects who were randomized to Placebo arm received one dose of Romiplostim inadvertently and were summarized in Romiplostim 750 mcg and 500 mcg arm, respectively.

Romiplostim 500 µg

Romiplostim 750 µg

Placebo weekly via subcutaneous injection plus lenalidomide 10 mg orally once per day for 16 weeks

Romiplostim (AMG 531) 500 μg weekly by subcutaneous injection plus lenalidomide 10 mg orally once per day for 16 weeks

Romiplostim 500 μg

Romiplostim (AMG 531) 750 μg weekly by subcutaneous injection plus lenalidomide 10 mg orally once per day for 16 weeks

Romiplostim 750 μg

Total

Age Continuous

Sex: Female, Male

White or Caucasian

Black or African American

Hispanic or Latino

Race/Ethnicity, Customized

>1.0

Missing

IPSS scoring for risk of myelodysplastic syndrome: 0 = low, 0.5 - 1.0 = intermediate 1, 1.5 - 2.0 = intermediate 2, ≥ 2.5 = high

International Prognostic Scoring System (IPSS) Score

Study Director

Full Analysis Set, composed of all randomized participants

Occurrence of a Clinically Significant Thrombocytopenic Event

Lenalidomide Dose Reduction and Delay Due to Thrombocytopenia

Achieving an Overall Response (Complete Response (CR) or Partial Response (PR)) Determined by the Investigator Based on Modified International Working Group 2006 Response Criteria Guidelines

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pre-myeloid Cancer and Bone Marrow Failure Clinic Study	NCT02958462	Myeloid Maligna... Inherited Bone ... Clonal Expansio... Cytopenia Bone Marrow Fai... Clonal Cytopeni... Clonal Hematopo... Hematologic Neo... Hematopoietic a... Hereditary Neop... Idiopathic Cyto... Idiopathic Dysp... Low Risk Myelod...	Biospecimen Col... Bone Marrow Bio... Punch Biopsy Buccal Swab Clinical Evalua... Genetic Counsel... Quality-of-Life... Electronic Heal...	18 Years -	Mayo Clinic
A Study Investigate the Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Response of SLN124 in Adults With Alpha/Beta-thalassaemia and Very Low- and Low-risk Myelodysplastic Syndrome	NCT04718844	Non-transfusion... Low Risk Myelod... Very-Low Risk M...	SLN124 Placebo	18 Years -	Silence Therapeutics plc
A Study Investigate the Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Response of SLN124 in Adults With Alpha/Beta-thalassaemia and Very Low- and Low-risk Myelodysplastic Syndrome	NCT04718844	Non-transfusion... Low Risk Myelod... Very-Low Risk M...	SLN124 Placebo	18 Years -	Silence Therapeutics plc
Pre-myeloid Cancer and Bone Marrow Failure Clinic Study	NCT02958462	Myeloid Maligna... Inherited Bone ... Clonal Expansio... Cytopenia Bone Marrow Fai... Clonal Cytopeni... Clonal Hematopo... Hematologic Neo... Hematopoietic a... Hereditary Neop... Idiopathic Cyto... Idiopathic Dysp... Low Risk Myelod...	Biospecimen Col... Bone Marrow Bio... Punch Biopsy Buccal Swab Clinical Evalua... Genetic Counsel... Quality-of-Life... Electronic Heal...	18 Years -	Mayo Clinic
Efficacy and Safety of FG-4592 for Treatment of Anemia in Participants With Lower Risk Myelodysplastic Syndrome (MDS)	NCT03303066	Anemia Myelodysplastic...	FG-4592 Placebo	18 Years - 80 Years	FibroGen
A Safety and Efficacy Study to Evaluate AMG 531 Treatment in Subject With Myelodysplastic Syndrome Receiving Revlimid	NCT00418665	Myelodysplastic... Thrombocytopeni...	AMG 531 Placebo	18 Years -	Amgen

Spots Global Cancer Trial Database for low risk myelodysplastic syndrome