Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Rare Diseases

Syndrome

Leukemia

Preleukemia

Leukemia, Myelomonocytic, Chronic

Leukemia, Myelomonocytic, Juvenile

Myelodysplastic Syndromes

Anemia

Leukemia, Myelomonocytic, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Bone Marrow Diseases

Precancerous Conditions

Leukemia, Myeloid

Myeloproliferative Disorders

Myelodysplastic-Myeloproliferative Diseases

Chronic Disease

Disease Attributes

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Chronic Graft Versus Host Disease

Acute Graft Versus Host Disease

Chronic Myeloproliferative Disorders

Myelodysplastic/myeloproliferative Disease

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

All Drugs and Chemicals

Chrysarobin

Sotatercept is supplied as a lyophilized powder that is reconstituted using Water for Injection (WFI) and administered as a subcutaneous injection (SC) injection by the study staff at the clinical site.

Sotatercept

Rodrigo Ito, MD

The primary objective of this study is to determine a safe, tolerable and effective dose of sotatercept that results in the greatest frequency of improvement of anemia in patients diagnosed with low- or intermediate-1 risk myelodysplastic syndromes (MDS) or non-proliferative chronic myelomonocytic leukemia (CMML).

Study of Sotatercept for the Treatment of Anemia in low-or Intermediate-1 Risk Myelodysplastic Syndromes (MDS) or Non-proliferative Chronic Myelomonocytic Leukemia (CMML)

An Open-label, Randomized, Phase 2, Parallel, Dose-Ranging, Multicenter Study of Sotatercept for the Treatment of Patients With Anemia and Low or Intermediate-1 Risk Myelodysplastic Syndromes or Non-proliferative Chronic Myelomonocytic Leukemia (CMML)

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

The responder rate includes non-transfusion dependent efficacy (NTDE) participants and transfusion dependent efficacy (TDE) participants. For non-transfusion dependence efficacy (NTDE) participants who required \< 4 units of RBCs in the 8 weeks prior to start of therapy, HI-E was defined as an increase of \>=1.5 g/dL hemoglobin sustained for 56 days over a period of \>=8 weeks. For transfusion dependence efficacy (TDE) participants who required \>=4 units of RBCs in the 8 weeks prior to start of therapy, HI-E was defined as a decrease of \>= 4 units of RBCs transfused sustained for 56 days over a period of 8 weeks.

Time to first response = start date of first response (HI-E) - first dose date + 1 day. For NTDE participants (who required \< 4 units of RBCs in the 8 weeks prior to start of therapy), HI-E was defined as an increase of \>=1.5 g/dL hemoglobin sustained for 56 days over a period of \>=8 weeks. For TDE participants (who required \>=4 units of RBCs in the 8 weeks prior to start of therapy), HI-E was defined as a decrease of \>= 4 units of RBCs transfused sustained for 56 days over a period of 8 weeks.

The duration of HI-E response for participants who responded was (the last date of the consecutive hemoglobin \[Hgb\] measurements of the first \>=56 day interval) - (the first date of the consecutive Hgb measurements of the first \>=56 day interval) + 1 day.

Progression to AML used criteria by the International Working Group (IWG) Response Criteria in Myelodysplasia (Cheson, 2006). Progression is considered if any of the following are met: - \>=50% increase in blasts - \>=50% decrement from maximum remission/response levels in granulocytes or platelets - Reduction in Hgb concentration by \>=2 g/dL - Transfusion dependence This outcome was defined as a Kaplan-Meier estimate however few participants progressed so a Kaplan-Meier analysis could not be performed. Disclosed are time to progression values only for participants who did progress to AML.

Progression to events of higher risk MDS used criteria from the International Prognostic Scoring System for MDS (IPSS) which assigns a prognostic score (0=good and increasing in risk by half-grades with the top score outlined below) for three prognostic variables: - Marrow blasts (score 0-2.0) - Karyotype (score 0-1.0) - Cytopenias: neutrophil, platelets, and Hg counts (score 0-0.5) The three individual scores are summed resulting in a full range of 0- 3.5 and placed into risk categories 0 = low risk 0.5-1.0 = intermediate-1 risk 1.5-2.0 = intermediate-2 risk \>=2.5 = high risk This outcome was defined as a Kaplan-Meier estimate however few participants progressed so a Kaplan-Meier analysis could not be performed. Data reported represent event times (weeks) for participants who did progress to higher risk MDS categories.

Participants who had disease progression were considered to have events. Participants who died without acute myeloid leukemia (AML) were also considered to have events with the event date as the date of death. Those who did not have disease progression and who were lost to follow-up were censored at the last known disease progression assessment date. Participants without disease progression at the last follow-up contact were censored at the date of the last follow-up contact date. Disease Progression to AML used criteria by the International Working Group (IWG) Response Criteria in Myelodysplasia (Cheson, 2006). Progression is considered if any of the following are met: - \>=50% increase in blasts - \>=50% decrement from maximum remission/response levels in granulocytes or platelets - Reduction in hemoglobin (Hgb) concentration by \>=2 g/dL - Transfusion dependence

OS was defined as the time between start of treatment and the death/censored date. Participants who died (regardless of the cause of death) were considered to have an event. Participants who were alive at the end of the study, and participants who were lost to follow-up, were censored at the last date when subjects were known to be alive.

Maximum observed serum concentration, obtained directly from the observed concentration versus time data.

An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. Treatment-emergent adverse events (TEAEs) are defined as any AE occurring or worsening on or after the first treatment of the study medication and within 42 days after the last dose. The severity of AEs was graded based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.0 and the scale: Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life threatening Grade 5 = Death. Relation to study drug was determined by the investigator. A treatment-related TEAE is defined as TEAE which was considered to be related to the study drug and reported as 'Suspected' on the CRF. AEs with a missing relationship were treated as 'treatment-related' in data summaries.

The following were DLTs if the investigator suspected they were treatment related: 1. Increase to \>= 140 mmHg systolic blood pressure 2. Increase to \>=90 mmHg diastolic blood pressure 3. Increase to \>=140 systolic and increase \> 20 mmHg compared to baseline systolic 4. Increase to \>=90 mmHg diastolic and increase \> 20 mmHg compared to baseline diastolic 5. Introduction of new anti-hypertension medication during treatment 6. Increase in dose of baseline anti-hypertension medication during treatment 7. \>= Grade 2 (moderate severity or worse) hypertension as an adverse event

Number of participants who achieved RBC-independence was defined as participants who required no RBC-transfusions during a 56-day interval of erythroid hematological improvement (HI-E). NTDE = non-transfusion dependence efficacy participants who required \< 4 units of RBCs in the 8 weeks prior to start of therapy TDE = transfusion dependence efficacy participants who required \>=4 units of RBCs in the 8 weeks prior to start of therapy

Merck Sharp & Dohme LLC

Sotatercept 0.1 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to either the 0.1 mg/kg arm or the 0.3 mg/kg arm. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/5 subjects in Cycle 1 in the 0.1 mg/kg and 0.3 mg/kg treatment groups, the 0.5 mg/kg treatment group began inclusion in the randomization scheme.

Sotatercept 0.1 mg/kg

Sotatercept 0.3 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to either the 0.1 mg/kg arm or the 0.3 mg/kg arm. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/5 subjects in Cycle 1 in the 0.1 mg/kg and 0.3 mg/kg treatment groups, the 0.5 mg/kg treatment group began inclusion in the randomization scheme.

Sotatercept 0.3 mg/kg

Sotatercept 0.5 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/6 subjects in Cycle 1 in the 0.5 mg/ kg treatment group, the 1.0 mg/kg treatment group began inclusion in the randomization scheme.

Sotatercept 0.5 mg/kg

Sotatercept 1.0 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/6 subjects in Cycle 1 in the 1.0 mg/ kg treatment group, the 2.0 mg/kg treatment group began inclusion in the randomization scheme. Following evaluation of all treatment group data by the Steering Committee, enrollment continued only in the 1.0 mg/kg arm because the arm had the greatest frequency of erythroid hematological improvement (HI-E).

Sotatercept 1.0 mg/kg

Sotatercept 2.0 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. The 2.0 mg/kg sotatercept dose was reduced to 1.5 mg/kg for ongoing and newly enrolled participants by protocol amendment.

Sotatercept 2.0 mg/kg

Sotatercept 0.5 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/6 subjects in Cycle 1 in the 0.5 mg/kg treatment group, the 1.0 mg/kg treatment group began inclusion in the randomization scheme.

Sotatercept 1.0 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/6 subjects in Cycle 1 in the 1.0 mg/kg treatment group, the 2.0 mg/kg treatment group began inclusion in the randomization scheme. Following evaluation of all treatment group data by the Steering Committee, enrollment continued only in the 1.0 mg/kg arm because the arm had the greatest frequency of erythroid hematological improvement (HI-E).

Total

Age, Continuous

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

France

Region of Enrollment

Height

Weight

Erythropoietin level

RBC units transfused during 56 days prior to the start of treatment.

Red Blood Cell (RBC) Transfusion Burden Categories

Number of Previous Erythropoiesis-Stimulating Agents (ESA) Therapies for Myelodysplastic Syndromes

Number of Previous Non-ESA Agents for Myelodysplastic Syndromes (MDS)

The International Prognostic Scoring System for MDS (IPSS) assigns a prognostic score (0=good and increasing in risk by half-grades with the top score outlined below) for three prognostic variables: - Marrow blasts (score 0-2.0) - Karyotype (score 0-1.0) - Cytopenias: neutrophil, platelets, and Hg counts (score 0-0.5) The three individual scores are summed resulting in a full range of 0- 3.5 and placed into risk categories - 0 = low risk - 0.5-1.0 = intermediate-1 risk - 1.5-2.0 = intermediate-2 risk - \>=2.5 = high risk

International Prognostic Scoring System (IPSS) Risk Category

Erythropoietin Level

Senior Vice President, Global Clinical Development

All participants

NTDE subpopulation

TDE subpopulation

Efficacy Evaluable Population: all participants who take at least one dose of study medication and have baseline and at least one post-baseline assessment of efficacy without major deviation from protocol.

Percentage of Participants With Erythroid Hematological Improvement (HI-E) Starting Before the Completion of Five Cycles of Treatment (Responder Rate)

Efficacy Evaluable Population of participants who responded

Time to Erythroid Hematological Improvement (HI-E) Response

Duration of Erythroid Hematological Improvement (HI-E)

Efficacy Evaluable Population of participants who progressed to AML

Time to Progression to Acute Myeloid Leukemia (AML) for Participants Who Had Progression

Efficacy Evaluable Population of participants who progressed to high risk MDS categories

Time to Progression to Events of Higher Risk Myelodysplastic Syndromes (MDS) Using the International Prognostic Scoring System (IPSS) For Participants Who Had Progression

Kaplan-Meier Estimates for Progression-free Survival

Kaplan-Meier Estimates for Overall Survival (OS)

Cycle 1 Day 8

Cycle 1 Day 15

Cycle 2 Day 1

Pharmacokinetic (PK) population includes participants with a sufficient amount of post-dose quantifiable PK sotatercept profile.

Pharmacokinetic Parameters of Sotatercept: Serum Concentration at Various Study Timepoints

>= 1 Treatment-emergent adverse event (TEAE)

>=1 Treatment-related TEAE

>=1 Serious TEAE

>=1 Serious TEAE related to treatment

>=1 TEAE severity 3 or 4

>=1 TEAE severity grade 3/4 related to treatment

>=1 TEAE leading to death

>=1 TEAE leading to dose reduction

>=1 TEAE leading to dose interruption

>=1 TEAE leading to dose interruption + reduction

>= 1 TEAE leading to drug discontinuation

Safety population: all participants who receive at least one dose of study medication.

Participants With Treatment-Emergent Adverse Events (TEAE)

1. Increase to >= 140 mmHg systolic

2. Increase to >=90 mmHg diastolic

3. =140 systolic and increase > 20 mmHg base

4. >=90 mmHg diastolic and increase > 20 mmHg base

5. Introduction of new anti-hypertension med

6. Incre in dose of baseline anti-hypertension med

7.>= Grade 2 hypertension TEAE

Dose Limiting Toxicities (DLTs)

Number of Participants Who Achieved Red Blood Cell (RBC)-Transfusion Independence During the Erythroid Hematological Improvement (HI-E) Interval

Overall Study

Immune System Diseases

Behaviors and Mental Disorders

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Leukemia, B-Cell

Quality of Life

Chronic Lymphocytic Leukemia

Hematinics

Epoetin Alfa

epoetin alfa

Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial

The purpose of this study is to evaluate the effect of treatment with epoetin alfa versus placebo on the percentage of red blood cells in anemic patients with chronic lymphocytic (white blood cell) leukemia and its effect on the patients' quality-of-life. Epoetin alfa is a genetically engineered protein that stimulates red blood cell production.

Cancer patients often experience anemia due to the disease itself, chemotherapy, or both. Quality of life is also affected, in part because of the fatigue associated with anemia. Previous studies with epoetin alfa have suggested that achieving a higher hemoglobin level may improve the quality of life and help patients live longer. This is a 12-week, double-blind, placebo-controlled, multicenter study to determine the effect of treatment with epoetin alfa on the percentage of red blood cells in anemic patients with chronic white blood cell leukemia. At the start of the study, patients were either receiving no chemotherapy, single-agent chemotherapy, and/or were on prednisone (steroid) treatment. Patients will be randomly assigned 2:1 to receive either epoetin alfa or placebo. Patients receiving epoetin alfa will receive subcutaneous (under the skin) epoetin alfa injections 3 times per week and patients on placebo will receive an equal volume of matching placebo, injected subcutaneously 3 times per week. Based on patients' rate of increase in red blood cell percentage, the original dose of 150 units per kilogram 3 times per week may be raised gradually to 300 units per kilogram 3 times per week, to reach a target red blood cell percentage of 38% to 40%. Patients achieving the target red blood cell percentage will be eligible for a 12-week open-label extension of the study, which will focus on safety findings. Effectiveness will be determined by the proportion of patients who reach the target red blood cell percentage of 38% to 40% by the end of the study, the number of transfusions required, the proportion of patients achieving a red blood cell percentage of 38% to 40% at any time during the study, and changes in quality of life parameters. Safety evaluations, including the incidence of adverse events, laboratory tests, and vital signs, will be performed throughout the study. The hypothesis of the study is that epoetin alfa will be superior to placebo in increasing the percentage of red blood cells to the target level, reducing the number of transfusions required, and improving the quality of life. Epoetin alfa 150 units per kilogram 3 times weekly subcutaneously for 12 weeks. Individualized dose increases of 50 mg/week depend on red blood cell response, up to a maximum 300 units per kilogram 3 times per week to obtain the target level of 38% to 40% red blood cells.

Epoetin Alfa for the Treatment of Anemia Resulting From Chronic Lymphocytic Leukemia

The Effect of Subcutaneous r-HuEPO in Patients With Chronic Lymphocytic Leukemia

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Thrombocytopenia

Patients allocated to the therapeutic platelet transfusion group will not receive routine prophylactic platelet transfusions.

Patients allocated to the prophylactic platelet transfusions will receive a platelet transfusion (a single dose of random donor platelets (4 unit pool or random donor platelets or one apheresis unit) when the measured platelet count is \< 10 x 109/L.

Patients allocated to the therapeutic platelet transfusion group will not receive routine prophylactic platelet transfusions. Platelet transfusions will be given to treat documented clinically relevant bleeding defined as WHO bleeding of grade 2 or greater. Patients may be transfused at the discretion of the treating physician. The indication for all platelet transfusions will be recorded by asking the ordering physician.

Patients allocated to the prophylactic platelet transfusions will receive a platelet transfusion when the measured platelet count is \< 10 x 109/L. Patients may receive additional platelet transfusions at the discretion of the treating physician. The indication for all platelet transfusions will be recorded.

Platelet Transfusion

Alan Tinmouth, MD, MSc

As a result of the underlying disease or its therapy, it is common for patients with blood cancers to have low platelet counts. While platelet transfusions may be beneficial in preventing or treating bleeding symptoms, in circumstances where the risk of bleeding is low they may be unnecessary or even harmful. As a blood product, transfusion of platelets may be associated with infectious or allergic complications, and frequent hospital visits for transfusion may adversely affect quality of life. Additionally, the potentially overuse of platelet products places a burden on health care resources.

The benefit of the current practice of prophylactic platelet transfusions to prevent hemorrhage is unknown. The randomized data that exists is more than 25 years old and not informative given methodological limitations and the changing standards of supportive care. An alternative, therapeutic, strategy involves only administering platelets to control active bleeding.

The standard of practice in inpatients receiving high dose chemotherapy (either for acute leukemia or as part of stem cell transplantation) is prophylactic platelet transfusions. In outpatients not receiving high dose chemotherapy, the risk of bleeding is significantly lower. No randomized trials have examined the optimal platelet transfusion strategy in outpatients with blood cancers undergoing supportive or palliative therapy. Thus the potential benefit of prophylactic transfusions in the outpatient setting is unknown.

The investigators propose to perform a pilot randomized controlled trial to determine if a larger trial is possible. The ultimate goal is to determine if a strategy of therapeutic platelet transfusions is safe and effective in outpatients with blood cancers and low platelet counts.

Randomization:

A local study nurse will use a web-based randomization system (permuted random blocks of two or four patients) to allocate consenting patients. Medical and research staff and investigators will be blinded to randomization scheme.

Study Duration and Follow-up:

All patients will be assigned to either a therapeutic or prophylactic platelet transfusion for a 6-month period. This period of time will allow us to assess our primary feasibility outcomes of enrollment, compliance with transfusion protocols, and completion of bleeding evaluations and quality of life questionnaires by patients.

Patients in both groups will have their CBC measured at least weekly while on study. More frequent monitoring of the platelet count may be performed at the discretion of the treating physician. The research team will clinically assess patients within 1 week (+/- 3 days) of randomization, and monthly thereafter. Patients will be asked to report any non-cutaneous grade 2 or greater bleeding immediately to their treating physicians and the study team. All the self-assessments of bleeding will be reviewed at each patient visit to ensure that all clinically relevant bleeding episodes have been captured.

Patients whose platelet count recovers to greater than 20 x 109/L for at least six weeks will be taken off the weekly platelet count monitoring as reflects clinical practice. They will continue to be monitored for the duration of the study. If their platelet count falls to 10 x 109/L or below then they will be restarted on the monitoring and previous transfusion protocol.

Data Collection:

Baseline Data - The following clinical and laboratory data will be collected at the time of enrolment: (1) demographic data, (2) diagnosis including date and disease stage, (3) prior chemotherapy, (4) ECOG performance status, (5) comorbidites, (6) previous platelet and red cell transfusions, (7) red cell transfusion history, (8) prior bleeding events, (9) quality of life (EQ5D) (10) routine bloodwork

Transfusions:

All platelet and red cell transfusions will be recorded including date and number of units. For platelet transfusions, the type of platelet product (e.g. apheresis or buffy coat) and ABO compatibility will recorded. Additionally, the indication for all transfusions (prophylactic or to treat bleeding) will be obtained from the attending physician.

Bleeding Assessment:

Participants will be asked to complete a simple bleeding questionnaire on a daily basis which has been previously tested and used in outpatients with thrombocytopenia. Patients will receive a short training session and written material on how to complete the form. A bleeding assessment will be performed at all study follow-up visits (interview, physical exam and review of daily bleeding forms). Bleeding events will be assigned a bleeding grade by the study personnel. A final bleeding grade will be assigned by an adjudication panel of 2 blinded physicians who will independently assign bleeding scores. Any discrepancies in bleeding scores will be resolved by consensus.

Quality of Life:

Quality of life will be measured using the EQ-5D. The EQ-5D is a validated tool for measurement of health-related quality of life there is a precedent for its use in transfusion medicine trials. Quality of life assessments will be performed at baseline and at all subsequent patient visits.

Outpatient Platelet Transfusions in Myelodysplastic Syndromes and Leukemia: The OPTIMAL Pilot

Overall enrollment, off protocol transfusions per each randomized group, total number of platelet transfusions per group and patient compliance with daily self assessment of bleeding will be evaluated.

Assessments will include:

1. Non-cutaneous Grade 2 bleeding or higher by the World Heath Organization (WHO) bleeding assessment scale 28(Appendix B)
2. Grade 3 bleeding or higher
3. Time from randomization to first bleeding event of grade 3 of higher
4. Total number of red cell transfusion per group
5. Total number of hospital days per group
6. Number of completed daily bleeding assessments per group
7. Quality of life
8. Mortality

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Sotatercept for the Treatment of Anemia in low-or Intermediate-1 Risk Myelodysplastic Syndromes (MDS) or Non-proliferative Chronic Myelomonocytic Leukemia (CMML)	NCT01736683	Anemia Myelodysplastic... Chronic Myelomo... Low to Intermed... Myelodysplastic... Chronic Myelomo...	Sotatercept	18 Years -	Merck Sharp & Dohme LLC
Epoetin Alfa for the Treatment of Anemia Resulting From Chronic Lymphocytic Leukemia	NCT00270049	Anemia Leukemia, Lymph... Leukemia, Lymph... Cancer Neoplasms Quality of Life	epoetin alfa	18 Years -	Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Outpatient Platelet Transfusions in Myelodysplastic Syndromes and Leukemia: The OPTIMAL Pilot	NCT01615146	Myelodysplastic... Leukemia	Platelet Transf...	18 Years -	Ottawa Hospital Research Institute
Epoetin Alfa for the Treatment of Anemia Resulting From Chronic Lymphocytic Leukemia	NCT00270049	Anemia Leukemia, Lymph... Leukemia, Lymph... Cancer Neoplasms Quality of Life	epoetin alfa	18 Years -	Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Spots Global Cancer Trial Database for transfusions

Every month we try and update this database with for transfusions cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.