Neoplasms

Blood and Lymph Conditions

All Conditions

Symptoms and General Pathology

Heart and Blood Diseases

Rare Diseases

Leukemia

Leukemia, Myelomonocytic, Chronic

Leukemia, Myelomonocytic, Juvenile

Myeloproliferative Disorders

Polycythemia Vera

Polycythemia

Primary Myelofibrosis

Thrombocytosis

Thrombocythemia, Essential

Bone Marrow Diseases

Hematologic Diseases

Leukemia, Myeloid

Neoplasms by Histologic Type

Myelodysplastic-Myeloproliferative Diseases

Chronic Disease

Disease Attributes

Bone Marrow Neoplasms

Hematologic Neoplasms

Blood Platelet Disorders

Hemostatic Disorders

Blood Coagulation Disorders

Hemorrhagic Disorders

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Chronic Graft Versus Host Disease

Chronic Myeloproliferative Disorders

Essential Thrombocythemia

Myelodysplastic/myeloproliferative Disease

Antineoplastic Agents

All Drugs and Chemicals

Talazoparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

0.25 mg (PO, QD) Talazoparib (Days 1-7) 200 mg (PO, BID) Pacritinib (Day 1-28, Lead in dosing of Pacritinib day -7 for the first cycle of treatment)

0.25 mg (PO, QD) Talazoparib (Days 1-14) 200 mg (PO, BID) Pacritinib (Day 1-28, Lead in dosing of Pacritinib day -7 for the first cycle of treatment)

0.5 mg (PO, QD) Talazoparib (Days 1-14) 200 mg (PO, BID) Pacritinib (Day 1-28, Lead in dosing of Pacritinib day -7 for the first cycle of treatment)

0.75 mg (PO, QD) Talazoparib (Days 1-14) 200 mg (PO, BID) Pacritinib (Day 1-28, Lead in dosing of Pacritinib day -7 for the first cycle of treatment)

1 mg (PO, QD) Talazoparib (Days 1-14) 200 mg (PO, BID) Pacritinib (Day 1-28, Lead in dosing of Pacritinib day -7 for the first cycle of treatment)

pacritinib in combination with talazoparib

pacritinib

Abigail Protocol Development Coordinator

Peter Abdelmessieh, DO, MSc

This is a prospective phase I dose-escalation study, with the primary objective to access the MTD and find the RP2D of talazoparib, given in combination with standard of care dosing of pacritinib.

This is a prospective phase I dose-escalation study, with the primary objective to access the MTD and find the RP2D of talazoparib, given in combination with standard of care dosing of pacritinib. Subjects must have a diagnosis of a myeloproliferative neoplasm and progressed or become intolerant to any JAK2 directed therapy. To be eligible for the therapy, patients are required to consent to a bone marrow biopsy at the beginning of study treatment. The treatment protocol involves initiating pacritinib on day -7 (lead-in phase, starting day -7 for cycle 1) with a standard of care dose of 200mg twice daily (BID). Subsequently, talazoparib will be given on day 1 of the treatment cycle. Cohort 1 will enroll patients at the starting dose of 0.25mg talazoparib for 14 days (dose level 1) and DLT (dose-limiting toxicity) rate will inform the subsequent dose levels (DLs).

Investigators plan to use a Bayesian Optimal Interval Design (BOIN) to determine the maximum tolerated dose (MTD) in patients with Ph-MPNs (Philadelphia chromosome negative myeloproliferative neoplasms) who have either not responded to or cannot tolerate ruxolitinib monotherapy. Subjects who are currently receiving JAK2-directed therapy will undergo a one-day washout period before starting the study treatment, as abrupt discontinuation of JAK2 inhibition can lead to side effects. This brief interval allows for the resolution of any lingering effects before initiating the new treatment. A bone marrow aspirate and or biopsy will be obtained to assess response to therapy at the end of each cycle of treatment (28 days), prior to beginning the next cycle as per physician discretion. Peripheral blood and bone marrow mononuclear cells will be checked for γ-H2AX (histone H2A family X) at set time points as a biomarker assay to assess for DNA damage in the same manner as the pre-clinical models published in our previous studies. Patients may remain on study drug unless they experience an unacceptable toxicity, fail to show a benefit, or they attain remission and it is felt by the investigator that they can proceed to an allogenic stem cell transplant.

Pacritinib w/ Talazoparib in Pts w/ Myeloproliferative Neoplasms Unresponsive to JAK2 Inhibition

Phase I Study Accessing the Safety of Pacritinib in Combination With Talazoparib in Patients With Myeloproliferative Neoplasms Unresponsive to Frontline JAK2 (Janus Kinase 2) Inhibition

To define the maximum tolerated dose (MTD) of talazoparib in combination with standard of care dosing of pacritinib in order to establish a recommended phase II dose (RP2D).

Rate of grade 3 or higher toxicities occurring with the combination of talazoparib and pacritinib in patients with MPNs that have failed to respond to one line of JAK2 directed therapy.

Response rate defined by a 35% or greater spleen volume reduction (SVR) or a \>25% reduction in total symptom score (TSS) at week 24 (per IWG-MTR (International Working Group for Myelofibrosis Research and Treatment) criteria).

Disease control rate, defined by improvement in quality of life measures, spleen size, and hematological recovery

Progression free survival, defined as the time of enrollment to disease progression

Overall survival, defined by time from enrollment to death from any cause

Fox Chase Cancer Center

Imetelstat

Motesanib diphosphate

Protein Kinase Inhibitors

Induction dosing of 9.4 mg/kg weekly, followed by intermittent maintenance dosing.

This is a phase II open-label study of single agent imetelstat in patients with essential thrombocytopenia or with polycythemia vera who have failed or are intolerant to at least one prior therapy, or who refuse standard therapy.

For patients with ET: To obtain a preliminary estimate of efficacy of imetelstat, as measured by best hematologic response within the first year of therapy in patients with ET who have failed or are intolerant to at least one prior therapy, or who have refused standard therapy.

For patients with PV: To obtain a preliminary estimate of efficacy of imetelstat, as measured by maintenance of Hct \< 45% in men and \< 42% in women (or pre-specified Hct count that is tolerable) without phlebotomy or myelosuppressive therapy within the first year of therapy in patients with PV who have failed or are intolerant to at least one prior therapy, or who have refused standard therapy.

Open Label Study to Evaluate the Activity of Imetelstat in Patients With Essential Thrombocythemia or Polycythemia Vera

A Phase II Trial to Evaluate the Activity of Imetelstat (GRN163L) in Patients With Essential Thrombocythemia or Polycythemia Vera Who Require Cytoreduction and Have Failed or Are Intolerant to Previous Therapy, or Who Refuse Standard Therapy

Primary objectives are as follows: ET patients - best hematologic response within the first year of therapy and PV patients - maintenance of Hct \< 45% in men and \< 42% in women (or pre-specified Hct count that is tolerable) without phlebotomy or myelosuppressive therapy within the first year of therapy. Secondary objectives, to determine the durability of hematologic response and to determine the rate of phlebotomy required within the first year of therapy.

The safety and tolerability of imtelstat will be assessed by the incidence, nature, relatedness and severity of adverse events, laboratory abnormalities and vital signs.

Geron Corporation

The three main chronic myeloproliferative disorders are polycythemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (IMF). These are clonal neoplastic diseases characterized by proliferation of one or more hematopoietic lineages. Recently a mutation of the Janus Kinase 2 (JAK2) gene that leads to the substitution of phenylalanine for valine at position 617 of the JAK2 protein, JAK2 V617F, has been found in 76% to 97% of patients with PV, 29% to 57% of patients with ET and 50% of patients with IMF. This mutation confers constitutive activity on to the JAK2 protein and appears to play an important role in the pathobiology of these conditions. However, not all patients with myeloproliferative disorders have this mutation and it may not be the primary cause of these diseases. The primary goal of this prospective natural history study is to investigate the molecular basis of these diseases in groups of patients who have JAK2 V617F and in those who do not. A second goal is to identify biomarkers for PV and the other myeloproliferative disorders that are easier to measure than JAK2 V617F. Approximately, 150 patients with myeloproliferative disorders will be studied over 3 years. The studies will involve the collection of 40 mL to 50 mL of peripheral blood from each subject. The blood will be used to assess neutrophil gene and protein expression, gene polymorphisms, and plasma protein levels.

Molecular Changes and Biomarkers in Chronic Myeloproliferative Disorders

National Institutes of Health Clinical Center (CC)

60 mg bid - 120 mg bid for an 18 weeks (126 days) treatment duration

lestaurtinib

This is an 18-week open-label, multicenter study to evaluate the efficacy and tolerability of CEP-701 (lestaurtinib) treatment in patients with Polycythemia Vera (PV) and patients with Essential Thrombocytosis (ET).

This is an 18-week open-label, multicenter study to evaluate the efficacy and tolerability of CEP-701 (lestaurtinib) treatment at a dosage of 80 mg bid for 18 weeks (126 days) in patients with Polycythemia Vera (PV) who have abnormal baseline neutrophil counts or require hydroxyurea therapy and patients with Essential Thrombocytosis (ET) who require hydroxyurea therapy for disease control.

Open-Label Study of Oral CEP-701 (Lestaurtinib) in Patients With Polycythemia Vera or Essential Thrombocytosis

An Open-Label Study of Oral CEP-701 in Patients With Polycythemia Vera or Essential Thrombocytosis With the JAK2 V617F Mutation

Cephalon

Immune System Diseases

Syndrome

Lymphoma

Hodgkin Disease

Preleukemia

Myelodysplastic Syndromes

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Hodgkin Lymphoma

Acute Graft Versus Host Disease

Antirheumatic Agents

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Total Body Irradiation 1200cGy (150cGy given in 8 fractions twice a day six hours apart on days -4, -3, -2 and -1.

Fludarabine 30 mg/m\^2 given once a day for 3 days on days -7, -6 and -5 Cyclophosphamide 50mg/kg given one a day on days +3 and +4

Peripheral Blood Stem Cell Transplant

Scott R Solomon, MD

In this study, patients will receive a myeloablative preparative regimen consisting of fludarabine and total body irradiation (TBI), followed by a T cell replete, mobilized peripheral blood stem cell (PBSC) allograft from a partially matched related donor. All patients will receive post-transplant Cy in addition to standard post transplant immunosuppression with tacrolimus and MMF. The treatment protocol will be essentially identical to the prior study, with the exception of the substitution of TBI for Busulfan. The investigators hypothesize that this change will significantly reduce the risk of HC, while maintaining the efficacy of the transplant.

Historically, haploidentical HSCT has been associated with significant risks of graft rejection and severe graft versus host disease (GVHD), leading to high treatment related mortality and poor outcomes. The risk of engraftment failure and GVHD may be reduced in intensively conditioned recipients of grafts that have been rigorously depleted of T cells, but the risks of serious infection and death from prolonged immune compromise in these patients remains high. Recently, investigators from Johns Hopkins University demonstrated a new approach to haploidentical transplantation, utilizing a nonmyeloablative preparative regimen, followed by a T cell-replete bone marrow infusion and post-transplantation immunosuppression with high dose Cyclophosphamide (Cy), tacrolimus, and MMF. Clinical studies have shown this approach to be safe and effective with a low incidence of graft rejection, GVHD, and treatment-related mortality. Relapse represents the major cause of treatment failure in these patients, particularly with high-risk myeloid malignancies.

In order to decrease this relapse risk in high-risk patients, the investigators initiated a myeloablative haploidentical HSCT study in January 2009 utilizing Busulfan-based conditioning, post-transplant Cy, and PBSC, instead of BM, as the stem cell source. Outcomes of the 15 patients transplanted to date have been promising with 100% engraftment, low rates of treatment-related mortality, relapse and GVHD, and excellent survival rates. An unexpected outcome of the study was a higher-than-expected rate of BK virus-induced hemorrhagic cystitis (HC) occurring in 7 of 14 evaluable patients. Although there were no deaths attributable to HC, it was associated with significant morbidity in some patients.

HC is a recognized complication of allogeneic transplant therapy. Late onset HC, occurring after engraftment, is due almost exclusively to reactivation of the polyoma BK virus (BKV). Other important risk factors associated with HC include Busulfan-based conditioning, acute GVHD, HLA mismatched transplants, and use of bone marrow as the stem cell source. TBI-based conditioning, prior to myeloablative allogeneic transplant, has been associated with significantly less HC than Busulfan-based conditioning in both retrospective and prospective randomized trials.

Eighteen patients will be accrued to this study. The primary end point of this study is the incidence of HC. The investigators will also examine the incidence of acute and chronic GVHD, engraftment, degree of donor-host chimerism, transplant related morbidity and mortality, as well as disease-free and overall survival. Stopping rules will minimize the risk of untoward or unexpected side effects.

Total Body Irradiation/Fludarabine Based Ablative Haploidentical Transplant for Hematologic Diseases

A Phase II Trial of Total Body Irradiation-Based Myeloablative Conditioning and Transplantation of Partially HLA-Mismatched Peripheral Blood Stem Cells for Patients With Hematologic Malignancies

1.1 To estimate the incidence of BK virus-associated hemorrhagic cystitis following a TBI-based myeloablative haploidentical HSCT in patients with high risk hematologic malignancies.

To obtain estimate of overall survival (OS)

Characterize donor hematopoietic chimerism in peripheral blood at day 30 after HSCT.

Blood and Marrow Transplant Group of Georgia

Northside Hospital, Inc.

Haplo transplant

Peripheral Blood Stem Cell Transplant: Total Body Irradiation 1200cGy (150cGy given in 8 fractions twice a day six hours apart on days -4, -3, -2 and -1.

Fludarabine 30 mg/m2 given once a day for 3 days on days -7, -6 and -5 Cyclophosphamide 50mg/kg given one a day on days +3 and +4

Myeloablative Haploidentical Transplant

Age, Categorical

Sex: Female, Male

White

Black/African America

Race/Ethnicity, Customized

Scott R. Solomon, MD (Principal Investigator)

Percentage of Patients Experiencing Hemorrhagic Cystitis Post Transplant

Survival

Percentage of Participatns With Donor Chimerism Post-transplant

Disease Free Survival (DFS) Percentage

Non-relapsed Mortality (NRM) Percentage

Relapse Rate

Cumulative Incidence of Chronic Graft-versus-host Disease

Haplo transplant

Peripheral Blood Stem Cell Transplant: Total Body Irradiation 1200cGy (150cGy given in 8 fractions twice a day six hours apart on days -4, -3, -2 and -1.

Fludarabine 30 mg/m\^2 given once a day for 3 days on days -7, -6 and -5 Cyclophosphamide 50mg/kg given one a day on days +3 and +4

Patient follow up x6 months

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pacritinib w/ Talazoparib in Pts w/ Myeloproliferative Neoplasms Unresponsive to JAK2 Inhibition	NCT06218628	Primary Myelofi... Post-polycythem... Post-essential ... Chronic Myelomo... Polycythemia Ve... Essential Throm...	Talazoparib pacritinib	18 Years -	Fox Chase Cancer Center
Open Label Study to Evaluate the Activity of Imetelstat in Patients With Essential Thrombocythemia or Polycythemia Vera	NCT01243073	Essential Throm... Polycythemia Ve...	Imetelstat	18 Years -	Geron Corporation
Molecular Changes and Biomarkers in Chronic Myeloproliferative Disorders	NCT00433862	Polycythemia Ve... Essential Throm... Idiopathic Myel... Neutrophils Chronic Myelopr...		18 Years -	National Institutes of Health Clinical Center (CC)
Open-Label Study of Oral CEP-701 (Lestaurtinib) in Patients With Polycythemia Vera or Essential Thrombocytosis	NCT00586651	Polycythemia Ve... Essential Throm...	lestaurtinib	18 Years - 99 Years	Teva Branded Pharmaceutical Products R&D, Inc.
Molecular Changes and Biomarkers in Chronic Myeloproliferative Disorders	NCT00433862	Polycythemia Ve... Essential Throm... Idiopathic Myel... Neutrophils Chronic Myelopr...		18 Years -	National Institutes of Health Clinical Center (CC)
Total Body Irradiation/Fludarabine Based Ablative Haploidentical Transplant for Hematologic Diseases	NCT01336712	Chronic Leukemi... Acute Leukemia Hodgkin's Disea... Non-Hodgkin's L... Myelodysplastic...	Peripheral Bloo...	18 Years - 60 Years	Northside Hospital, Inc.

Spots Global Cancer Trial Database for essential thrombocytosis