Neoplasms

Blood and Lymph Conditions

All Conditions

Heart and Blood Diseases

Rare Diseases

Polycythemia Vera

Polycythemia

Primary Myelofibrosis

Thrombocytosis

Thrombocythemia, Essential

Myeloproliferative Disorders

Bone Marrow Diseases

Hematologic Diseases

Bone Marrow Neoplasms

Hematologic Neoplasms

Blood Platelet Disorders

Hemostatic Disorders

Blood Coagulation Disorders

Hemorrhagic Disorders

Essential Thrombocythemia

Chronic Myeloproliferative Disorders

Patients receive LOXL2 inhibitor PAT-1251 PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

LOXL2 Inhibitor PAT-1251

Quality-of-Life Assessment

Questionnaire Administration

Lucia Masarova

This phase II trial studies how well PAT-1251 works in treating patients with primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocytosis myelofibrosis. PAT-1251 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To determine the efficacy of LOXL2 inhibitor PAT-1251 (PAT-1251) as therapy for primary myelofibrosis (PMF), post-polycythemia vera (PV) myelofibrosis (MF), and post-essential thrombocytosis (ET) MF.

II. To determine the objective response of PAT-1251 treatment which is defined as CR (complete remission) + PR (partial remission) + CI (clinical improvement) after three and six cycles of treatment.

SECONDARY OBJECTIVES:

I. To determine the safety of PAT-1251 as therapy for PMF, post-PV MF and post-ET MF.

II. To determine time to response and response duration. III. To assess changes in symptom burden as assessed by Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS).

EXPLORATORY OBJECTIVES:

I. To explore changes in bone marrow reticulin fibrosis, collagen, osteosclerosis (grading).

II. To determine the percent target engagement based on a plasma target engagement assay after treatment with PAT-1251.

OUTLINE:

Patients receive LOXL2 inhibitor PAT-1251 orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days.

PAT-1251 in Treating Patients With Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocytosis Myelofibrosis

Open Label Phase 2 Single Agent Study of PAT-1251 in Patients With Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (Post-PV MF), or Post-Essential Thrombocytosis Myelofibrosis (Post-ET MF)

Descriptive statistics including plots, mean, median and standard deviations will be used to summarize data. For continuous outcomes, t-test and analysis of variance (ANOVA) will be used to compare outcome measures across patient characteristics. Dunnett's and Tukey's test that properly adjust for multiplicity in multiple tests will be implemented. Pair-wise comparisons will be performed using pre- and post-therapy samples from each patient. The chi-square test or Fisher's exact test will be used to test the association between two categorical variables such as disease state and performance status.

The percent target engagement based on a plasma target engagement assay after treatment with LOXL2 inhibitor PAT-1251 will be determined. Descriptive statistics including plots, mean, median and standard deviations will be used to summarize data. For continuous outcomes, t-test and ANOVA will be used to compare outcome measures across patient characteristics. Dunnett's and Tukey's test that properly adjust for multiplicity in multiple tests will be implemented. Pair-wise comparisons will be performed using pre- and post-therapy samples from each patient. The chi-square test or Fisher's exact test will be used to test the association between two categorical variables such as disease state and performance status.

Will be defined as complete remission (CR) + partial remission (PR) + clinical improvement (CI). Responses will be categorized according to the revised International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European Leukemia Net (ELN) consensus criteria for myelofibrosis. Will be estimated along with the exact 95% confidence interval.

Toxicity is defined as grade 3-4 clinically relevant non-hematologic toxicity or a serious adverse event that is at least possibly drug related (Common Terminology Criteria for Adverse Events version 4.03) and occurs anytime during the treatment. The method of Thall, Simon and Estey will be used for toxicity monitoring. Safety data will be summarized by category, severity and frequency. The proportion of patients with AEs will be estimated, along with the Bayesian 95% credible intervals.

The distribution will be estimated by Kaplan-Meier curves.

Will be assessed by Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score.

Will be used to explore improvements in anemia and the following outcomes will be summarized: mean changes in hemoglobin at monthly intervals.

Will be used to explore improvements in the transfusion dependence. The following outcomes will be summarized: mean changes in hemoglobin at monthly intervals.

Will be summarized if the patient is not requiring transfusions on the study who experience an increase of 2 g/dL in their hemoglobin.

The proportion of transfusion dependent patients (defined as requiring a transfusion of 2 units packed red blood cells (PRBCs) monthly for 3 months (12 weeks) prior to starting the trial) who become transfusion independent (not requiring a transfusion of PRBCs over a period of 3 months (12 weeks) while on study) will be summarized.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Durvalumab

Atezolizumab

Immunoglobulins

Immunoglobulin G

Immunoglobulins, Intravenous

Antibodies, Monoclonal

Antineoplastic Agents, Immunological

Immunologic Factors

Patients receive durvalumab IV over approximately 1 hour on day 1. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients with SD, no new inter-current illness, and no unacceptable toxicity, may continue treatment beyond 3 courses.

Laboratory Biomarker Analysis

Brady Stein, MD, MHS

The main purpose of this investigational research study is to determine how safe and tolerable the study drug, MEDI4736 (Durvalumab), is in patients with myelofibrosis (MF). The study drug belongs to a group of drugs called immune checkpoint inhibitors, which have shown promise in other forms of cancer, such as melanoma and lung cancer. One of the effects that this drug has is to activate the patient's own natural immune system. The purpose of this study is to examine the safety and tolerability of the study drug, to study how effective it is at treating patients with myelofibrosis, and to explore how certain markers in the patient's blood and/or bone marrow may be affected by the study drug.

PRIMARY OBJECTIVES:

I. To determine the safety profile of anti-programmed cell death 1 ligand 1 (PDL1) therapy in patients with myelofibrosis.

SECONDARY OBJECTIVES:

I. Changes in MF symptom burden. II. Changes in spleen size. III. Blood and/or bone marrow samples.

TERTIARY OBJECTIVES:

I. To determine the rate of lymphocyte subset response to anti-PDL1 therapy, as measured by the percent increase in cluster of differentiation (CD)4+CD25+PD-L1+ T-lymphocytes and CD4+CD62L+CD127+ T lymphocytes in post-treatment peripheral blood samples.

II. To characterize changes in the cytokine profile in response to anti-PDL1 therapy.

III. To measure soluble PDL1 by enzyme-linked immunosorbent assay (ELISA) in post-treatment blood and/or bone marrow samples and programmed cell death-1 (PD1)/PDL1 by immunohistochemistry on bone marrow samples and correlate with treatment response.

OUTLINE:

Patients receive durvalumab intravenously (IV) over approximately 1 hour on day 1. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease (SD), no new inter-current illness, and no unacceptable toxicity, may continue treatment beyond 3 courses.

Patients will be followed every 3 months for up to two years starting from Day 1.

Durvalumab in Treating Patients With Primary, Post-Polycythemia Vera, or Post-Essential Thrombocythemia Myelofibrosis

A Phase 1, Single Arm, Single Center Pilot Study of Medi4736, an Anti-Pdl1 Therapy, for Patients With Myelofibrosis

Determine the rate of lymphocyte subset response to anti-PDL1 therapy as measured by the percent increase in lymphocytes in post-treatment peripheral blood samples.

Blood samples will be used to assess any change in the cytokine profile in response to anti-PDL1 therapy.

To measure soluble PDL1 by ELISA in post-treatment blood and/or bone marrow samples along with PD1/PDL1 by immunohistochemistry on bone marrow samples and correlate both with treatment response.

To determine the safety profile of anti-PDL1 therapy in patients with myelofibrosis, adverse events will be assessed by number, frequency, and severity according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.

Changes in MF symptom burden will be assessed using the validated Patient Reported Outcome tool called the Myeloproliferative Neoplasm (MPN)-Symptom Assessment Form (SAF).

Change in spleen size will be assessed by physical examination (palpation) OR ultrasound as part of standard of care.

Response to anti-PDL1 treatment will be defined in accordance with the revised/modified International Working Group (IWG) Response Criteria and will be assessed by blood samples.

Response to anti-PDL1 treatment will be defined in accordance with the revised/modified International Working Group (IWG) Response Criteria and will be assessed by bone marrow samples.

Celgene

The Leukemia and Lymphoma Society

Northwestern University

Symptoms and General Pathology

Digestive System Diseases

Splenomegaly

Hepatomegaly

Hypertrophy

Pathological Conditions, Anatomical

Liver Diseases

Gastrointestinal Diseases

Nivolumab

Immune Checkpoint Inhibitors

Patients receive nivolumab IV over 60 minutes once every 2 weeks for 8 doses and then once every 12 weeks thereafter. Treatment may continue for up to 4 years in the absence of disease progression or unacceptable toxicity.

Srdan Verstovsek

This phase II trial studies how well nivolumab works in treating patients with primary myelofibrosis, post-essential thrombocythemia myelofibrosis, or post-polycythemia vera myelofibrosis. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

PRIMARY OBJECTIVES:

I. To determine the efficacy/clinical activity of nivolumab in patients with myelofibrosis (MF).

SECONDARY OBJECTIVES:

I. To determine the safety of nivolumab in patients with MF.

TERTIARY OBJECTIVES:

I. To explore time to response and duration of response. II. To assess changes in symptom burden. III. To explore changes in bone marrow fibrosis. IV. To explore changes in Janus kinase 2 valine at amino acid position 617 (JAK2V617F) (or other molecular marker) allele burden or changes in cytogenetic abnormalities.

OUTLINE:

Patients receive nivolumab intravenously (IV) over 60 minutes once every 2 weeks for 8 doses and then once every 12 weeks thereafter. Treatment may continue for up to 4 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30, 60, and 100 days.

Nivolumab in Treating Patients With Primary Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis, or Post-Polycythemia Vera Myelofibrosis

Phase 2 Study of Nivolumab in Patients With Primary Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis, or Post-Polycythemia Vera Myelofibrosis

Responses will be categorized according to the revised International Working Group-Myeloproliferative Neoplasms Research and Treatment and European LeukmiaNet consensus criteria for myelofibrosis.

Patients receive nivolumab IV over 60 minutes once every 2 weeks for 8 doses and then once every 12 weeks thereafter. Treatment may continue for up to 4 years in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis: Correlative studies

Nivolumab: Given IV

Quality-of-Life Assessment: Ancillary studies

Treatment (Nivolumab)

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Srdan Verstovsek, MD. Professor

Objective Response Rate, Defined as Complete Remission + Partial Remission + Clinical Improvement

Overall Study

Elotuzumab

Patients receive elotuzumab IV over 1-4 hours on days 1, 8, 15, and 22 of cycles 1-2. Beginning in cycle 3, patients receive elotuzumab IV over 1-4 hours on day 1. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.

Prithviraj Bose

This phase II trial investigates how well elotuzumab works in treating patients with JAK2-mutated myelofibrosis. Elotuzumab may help to control myelofibrosis and/or help to improve blood cell count and bone marrow function.

PRIMARY OBJECTIVE:

I. To obtain preliminary evidence of the efficacy of elotuzumab in patients with myelofibrosis (MF) by estimating the rate of overall response by International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) 2013 criteria.

SECONDARY OBJECTIVES:

I. To characterize the safety and tolerability of elotuzumab in patients with MF.

II. To assess for improvements in cytopenias and bone marrow fibrosis grade, splenomegaly and disease-related symptoms.

III. To determine the duration of objective responses, if any, to elotuzumab. IV. To determine the time to next treatment.

EXPLORATORY OBJECTIVES:

I. To assess the proportion of circulating monocytes expressing the target of elotuzumab, SLAMF7, and any correlation of the same to the mutant JAK2 allele burden.

II. To assess baseline levels of IL-1Ralpha and other cytokines and the effects of elotuzumab, if any, on these over time.

III. To examine the effects of elotuzumab on fibrocyte count and differentiation, both in vitro and in vivo.

IV. To assess clonal evolution, if any, in MF patients on elotuzumab treatment.

OUTLINE:

Patients receive elotuzumab intravenously (IV) over 1-4 hours on days 1, 8, 15, and 22 of cycles 1-2. Beginning in cycle 3, patients receive elotuzumab IV over 1-4 hours on day 1. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then periodically thereafter.

Elotuzumab for the Treatment of JAK2-Mutated Myelofibrosis

A Pilot Study of the Anti-SLAMF7 Monoclonal Antibody, Elotuzumab, in Patients With Myelofibrosis

Fisher's exact test will be used to assess the associations between biomarker expression (high versus low) and outcomes. Wilcoxon singed rank test will be applied to assess the change of biomarkers from baseline.

OR is defined as CR (complete response) +PR (partial response) + CI (clinical improvement), where CI includes clinical improvements in anemia, splenomegaly and/or symptoms. Will estimate the OR rate, along with the exact 95% confidence interval.

The method of Thall, Simon and Estey will be used to monitor for safety. The severity of the toxicities will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 whenever possible. Will follow standard reporting guidelines for adverse events. Safety data will be summarized by category, severity and frequency.

The Kaplan-Meier method will be used to estimate the duration of response where median and 95% confidence interval will be reported.

The Kaplan-Meier method will be used to estimate the time to next treatment where median and 95% confidence interval will be reported.

Will be assessed according to European classification.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
PAT-1251 in Treating Patients With Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocytosis Myelofibrosis	NCT04054245	Myelofibrosis T... Polycythemia Ve... Primary Myelofi...	LOXL2 Inhibitor... Quality-of-Life... Questionnaire A...	18 Years -	M.D. Anderson Cancer Center
Durvalumab in Treating Patients With Primary, Post-Polycythemia Vera, or Post-Essential Thrombocythemia Myelofibrosis	NCT02871323	Polycythemia Ve... Primary Myelofi...	Durvalumab Laboratory Biom...	18 Years -	Northwestern University
Nivolumab in Treating Patients With Primary Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis, or Post-Polycythemia Vera Myelofibrosis	NCT02421354	Hepatomegaly Myelofibrosis T... Polycythemia Ve... Primary Myelofi... Splenomegaly	Laboratory Biom... Nivolumab Quality-of-Life...	18 Years -	M.D. Anderson Cancer Center
Nivolumab in Treating Patients With Primary Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis, or Post-Polycythemia Vera Myelofibrosis	NCT02421354	Hepatomegaly Myelofibrosis T... Polycythemia Ve... Primary Myelofi... Splenomegaly	Laboratory Biom... Nivolumab Quality-of-Life...	18 Years -	M.D. Anderson Cancer Center
Elotuzumab for the Treatment of JAK2-Mutated Myelofibrosis	NCT04517851	Myelofibrosis T... Polycythemia Ve... Primary Myelofi...	Elotuzumab Questionnaire A...	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for myelofibrosis transformation in essential thrombocythemia