Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Myeloproliferative Disorders

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Bone Marrow Diseases

Hematologic Diseases

Lymphosarcoma

Chronic Myeloproliferative Disorders

Micronutrients

Anti-Infective Agents

All Drugs and Chemicals

Antineoplastic Agents

Iodine

Cadexomer iodine

9H-purine-9-propanamine, 6-amino-8-((6-iodo-1,3-benzodioxol-5-yl)thio)-N-(1-methylethyl)-

This Phase 1 trial will be an open-label, dose-escalation study of single-agent PU-H71 in patients with advanced solid malignancies and lymphoma.

PU-H71 will be administered as an intravenous infusion over 1 hour two times a week on a 2 week on and 1 week off (Q21 day) schedule with a starting dose of 10 mg/m2. A Cycle on study will be defined as 21 days. The same schedule of administration will be used for all patients in this Phase I trial, and a MCRM (modified continual reassessment method)design will be employed. The MPN expansion may explore different dosing schedules.

PU-H71

Komal Jhaveri, MD

NOTE: This study is now recruiting only patients with Myeloproliferative Neoplasms (MPN). Dose escalation has been completed.

The purpose of this study is to test a new drug, called PU-H71 for the first time in humans, to find out what effects, good or bad, this new drug has on the patient and the cancer at different dose levels. PU-H71 blocks a protein called Heat Shock Protein-90 (Hsp90). Hsp90 is found in both normal and cancer cells, but may be more important in cancer cells. Attacking Hsp90 can stop the function of certain proteins that are needed for cancer cells to survive. The diseases that are part of this study may be especially sensitive to attacking Hsp90, and the investigators have seen signs of disease control in patients with MPN. This study is currently enrolling a cohort expansion for patients with myeloproliferative neoplasms (MPN).

The First-in-human Phase I Trial of PU-H71 in Patients With Advanced Malignancies

Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0. All patients enrolled who receive study drug will be eligible for these analyses.

Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0.

Blood will be drawn at the multiple time points for radioactive pharmacokinetic and metabolite analyses of 124I-PUH71

Toxicity will be monitored using NCI- Common Terminology Criteria for Adverse Events version (4.0).Patients receiving at least 3 out of 4 planned doses of study drug developing a drug-related toxicity will be eligible for these analyses.

complete response (CR), partial response (PR), stable disease (SD), duration of response, and progression free survival (PFS). Patients with measurable disease will be eligible for these analyses.

In a selected group of patients with advanced malignancies. All patients who undergo planned imaging will be eligible for this analysis.

Memorial Sloan Kettering Cancer Center

Heart and Blood Diseases

Polycythemia Vera

Polycythemia

Primary Myelofibrosis

Thrombocytosis

Thrombocythemia, Essential

Bone Marrow Neoplasms

Hematologic Neoplasms

Blood Platelet Disorders

Hemostatic Disorders

Blood Coagulation Disorders

Hemorrhagic Disorders

Essential Thrombocythemia

Self-administered Investigational Product (IP) (400 mg/day) on an outpatient basis, once daily preferably with food during an evening meal at the same time each day in consecutive 4-week (28-day) cycles.

A potent and selective inhibitor of JAK2 kinase activity

FEDRATINIB

Bristol-Myers Squibb

This is Single-Arm, Open-Label Efficacy and Safety Trial of Fedratinib in Subjects with DIPSS (Dynamic International Prognostic Scoring System)-Intermediate or High- Risk Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (post-PV MF), or Post-Essential Thrombocythemia Myelofibrosis (post-ET MF) and Previously Treated with Ruxolitinib.

The primary objective of the study is to evaluate the percentage of subjects with at least a 35% reduction in spleen size and one of the secondary objectives is to evaluate the safety of fedratinib.

This is Single-Arm, Open-Label Efficacy and Safety Trial of Fedratinib in Subjects with DIPSS (Dynamic International Prognostic Scoring System)-Intermediate or High- Risk Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (post-PV MF), or Post-Essential Thrombocythemia Myelofibrosis (post-ET MF) and Previously Treated with Ruxolitinib.

The spleen volume reduction at the end of Cycle 6 as the primary objective. The secondary objectives of the study are to further evaluate the safety and to assess and implement mitigation strategies for WE and for gastrointestinal (GI) adverse events.

The study will be at multiple centers to provide access to a broad population and have assurance the results are likely to have general applicability.

This is also conducted as an open-label study to collect efficacy and safety data with fedratinib use, no randomization or stratification will occur.

A Trial of Fedratinib in Subjects With DIPSS, Intermediate or High-Risk Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis and Previously Treated With Ruxolitinib

A Phase 3b, Multicenter, Single-Arm, Open-Label Efficacy and Safety Study of Fedratinib in Subjects With DIPSS (Dynamic International Prognostic Scoring System)-Intermediate or High-Risk Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (Post-PV MF), or Post-Essential Thrombocythemia Myelofibrosis (Post-ET MF) and Previously Treated With Ruxolitinib

Percentage of participants who have a ≥ 35% SVR at end of Cycle 6 as compared to baseline. Participants with a missing MRI/CT spleen volume at the end of Cycle 6 including those who meet the criteria for progression of splenomegaly before the end of Cycle 6 will be considered non-responders. Baseline value is defined as the last value or measurement taken prior to the first dose in the study

Number of participants and severity of all grade adverse events (AEs) and grade 3/4 AEs as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.

Number of participants and severity of treatment related all grade adverse events (AEs) and grade 3/4 AEs as per NCI CTCAE.

Mean change from baseline in hematology laboratory analysis - hemoglobin

Mean change from baseline in hematology laboratory analysis - erythrocytes.

Baseline value is defined as the last value or measurement taken prior to the first dose in the study

Mean change from baseline in hematology laboratory analysis - platelets, leukocytes and neutrophils.

Baseline value is defined as the last value or measurement taken prior to the first dose in the study

Mean change from baseline in hematology laboratory analysis - blasts/leukocytes

Baseline value is defined as the last value or measurement taken prior to the first dose in the study

Mean change from baseline in chemistry parameters analysis - ALT, AST, Amylase, Lipase

Baseline value is defined as the last value or measurement taken prior to the first dose in the study

Mean change from baseline in chemistry parameters analysis - Creatinine.

Baseline value is defined as the last value or measurement taken prior to the first dose in the study

Spleen response rate by palpation is the percentage of participants with a spleen response according to the IWG-MRT 2013 at the end of Cycle 6 as compared to baseline. This will be calculated for participants that have an enlarged spleen (≥ 5 cm below LCM) at baseline. Participants with a missing spleen size assessment at the end of Cycle 6 including those who meet the criteria for progression of splenomegaly before the end of Cycle 6 will be considered not to be responders.

Symptom response rate (SRR) is defined as the percentage of participants with ≥ 50% reduction from baseline to the end of Cycle 6 in total symptom score (TSS) measured by MFSAF version 4.0. The TSS will be defined as the sum of each of the 7 symptom scores. Participants without a baseline TSS \> 0 will be considered non-evaluable (due to no place for symptom reduction) for the SRR analysis. Participants with a missing TSS at the end of Cycle 6 or who had disease progression before the end of the Cycle 6 will be considered non-responders.

Durability of spleen volume response (DR) by MRI/CT is defined as time from the first documented spleen response (ie, ≥ 35% reduction in spleen volume) to the date of subsequent progressive disease (PD) (ie, ≥ 25% increase in spleen volume from baseline) or death, whichever is earlier. In the absence an event (ie, subsequent spleen volume reduction \< 35% before the analysis is performed), the DR will be censored at the date of the last valid assessment performed before the analysis performed date. Durability of spleen volume response by MRI/CT scan will be analyzed using Kaplan-Meier method.

Durability of spleen response by palpation (DRP) is defined as time from the date of first documented palpable spleen response, according to the IWG-MRT 2013 to the date of subsequent PD according to the IWG-MRT 2013 or death, whichever is earlier. Durability of spleen response by palpation according to the IWG-MRT 2013 criteria will be calculated for subjects that have an enlarged spleen at baseline (≥ 5 cm below LCM), and that have a spleen response by palpation. In the absence of an event (ie, no loss of spleen response by palpation) before the analysis is performed, the DRP will be censored at the date of the last valid assessment performed before the analysis performed date. Durability of spleen response by palpation will be analyzed using Kaplan-Meier (K-M) method.

Durability of symptoms response is defined as time from the first documented response in TSS (ie, reduction in TSS ≥ 50%) measured by MFSAF version 4.0 to the first documented TSS reduction \< 50%. In the absence of TSS reduction \< 50% before the analysis performed, the DSR will be censored at the date of the last valid assessment performed before the analysis performed date.

Number of participants with grade 3 or higher AEs: Nausea, Vomiting, Diarrhea and Encephalopathy including Wernicke's.

Number of participants with thiamine levels \< LLN.

LLN of thiamine is 70 nmol/L.

Number of participants with thiamine levels \> ULN.

ULN of thiamine is 180 nmol/L.

Impact Biomedicines, Inc., a wholly owned subsidiary of Celgene Corporation

Celgene

Adverse events will be analyzed in terms of TEAEs that are defined to be any event that begins or worsens in grade after the start of fedratinib through 30 days after the last dose.

Fedratinib

Fedratimib

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Efficacy Evaluable Population

All participants who enrolled and received at least one dose of fedratinib, had an evaluable spleen volume at baseline (based on MRI/CT scan) and at least one post-baseline response assessment by MRI/CT scan

EE Population

fedratinib treated participants with a Total Symptom Score (TSS) at baseline (eg, symptom score) \> 0 and at least 1 post baseline TSS assessment

MFSAF Population

All participants who enrolled and received at least one dose of fedratinib, and had an enlarged spleen ≥ 5 cm below LCM at baseline

Palpation evaluable population

Bristol-Myers Squibb Study Director

Percentage of Participants Who Have a ≥ 35% Spleen Volume Reduction (SVR) at End of Cycle 6

All grade

Grade 3/4

Number of Participants of All Grade Adverse Events (AEs) and Grade 3/4 AEs

Number of Participants and Severity of Treatment Related All Grade Adverse Events (AEs) and Grade 3/4 AEs

cycle 4 day 1

cycle 7 day 1

all treated participants with both baseline and post-baseline measurements

Mean Change From Baseline in Hematology Laboratory Analysis - Hemoglobin

Mean Change From Baseline in Hematology Laboratory Analysis - Erythrocytes

cycle 4 day 1 - platelets

cycle 7 day 1 - platelets

cycle 4 day 1 - leukocytes

cycle 7 day 1 - leukocytes

cycle 4 day 1 - neutrophils

cycle 7 day 1 - neutophils

Mean Change From Baseline in Hematology Laboratory Analysis - Platelets, Leukocytes and Neutrophils

Mean Change From Baseline in the Percentage of Blasts/Leukocytes in Hematology Laboratory Analysis

cycle 4 day 1 - ALT

cycle 7 day 1 - ALT

cycle 4 day 1 - AST

cycle 7 day 1 - AST

cycle 4 day 1 - Amylase

cycle 7 day 1 - Amylase

cycle 4 day 1 - Lipase

cycle 7 day 1 - Lipase

Mean Change From Baseline in Chemistry Parameters Analysis - ALT, AST, Amylase, Lipase

cycle 4 day 1 - Creatinine

cycle 7 day 1 - Creatinine

Mean Change From Baseline in Chemistry Parameters Analysis - Creatinine

Spleen Response Rate by Palpation

Symptom Response Rate

Durability of Spleen Volume Response by MRI/CT (DR)

Palpation Evaluable Population, responders only

Durability of Spleen Response by Palpation (DRP)

Durability of Symptom Response (DSR)

Nausea

Vomitting

Diarrhea

Encephalopathy including Wernicke's

Number of Participants With Grade 3 or Higher AEs: Nausea, Vomiting, Diarrhea and Encephalopathy Including Wernicke's.

Screening

Cycle 1

Cycle 2

Cycle 3

Cycle 6

Cycle 9

Cycle 12

Cycle 15

Cycle 18

Cycle 21

Cycle 24

Cycle 27

Cycle 30

End of Treatment

Number of Participants With Thiamine Levels < Lower Limit of Normal (LLN).

Number of Participants With Thiamine Levels > Upper Limit of Normal (ULN).

Overall Study

Digestive System Diseases

Thrombosis

Venous Thrombosis

Hypertension

Hypertension, Portal

Vascular Diseases

Embolism

Embolism and Thrombosis

Liver Diseases

Gastrointestinal Diseases

This is a one arm study. All patients will receive two screening tests (Doppler ultrasound, upper gastrointestinal endoscopy).

Upper gastrointestinal endoscopy and Doppler ultrasound

Vikas Gupta, MD, FRCP

This study involves screening for portal vein thrombosis and portal hypertension in patients with Philadelphia negative myeloproliferative neoplasms (MPNs). These include polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis.

Portal vein thrombosis and portal hypertension are serious complications that are often seen in myeloproliferative patients. These complications are usually diagnosed when patients become symptomatic, and are often already at an advanced stage. They can further progress to cause non-reversible damage to the liver, also called cirrhosis of the liver. As a result of this, patients often accumulate fluid in the abdomen which is ascites; and can develop swelling of veins in the lining of the esophagus known as varices. If untreated, varices have the risk of rupturing resulting in life-threatening bleeding. When diagnosed at an advanced stage, the treatment is usually supportive therapy and there are no treatments available at present which can reverse these conditions.

This study is looking at screening for these two conditions using Doppler ultrasound and upper gastrointestinal endoscopy.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
The First-in-human Phase I Trial of PU-H71 in Patients With Advanced Malignancies	NCT01393509	Metastatic Soli... Lymphoma Myeloproliferat...	PU-H71	18 Years -	Memorial Sloan Kettering Cancer Center
A Trial of Fedratinib in Subjects With DIPSS, Intermediate or High-Risk Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis and Previously Treated With Ruxolitinib	NCT03755518	Primary Myelofi... Post-Polycythem... Myelofibrosis Post-essential ...	FEDRATINIB	18 Years -	Celgene
Screening for Asymptomatic Portal Vein Thrombosis and Portal Hypertension in Patients With Philadelphia Negative Myeloproliferative Neoplasms	NCT01816256	Myeloproliferat... Polycythemia Ve... Essential Throm... Myelofibrosis (...	Upper gastroint...	-	University Health Network, Toronto

Spots Global Cancer Trial Database for myeloproliferative neoplasms (mpn)