Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Promyelocytic, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Acute Graft Versus Host Disease

Acute Promyelocytic Leukemia

Antineoplastic Agents

All Drugs and Chemicals

Idarubicin

Arsenic Trioxide

Arsenic trioxide

ATRA

Lionel ADES, MD

Lionel ADES, MD,PhD

To assess the role of Arsenic trioxide and/or ATRA during consolidation course in APL. It is hoped that the investigational arms will further increase the event-free survival at 2 years, with reduced toxicity and without increasing the relapse rate by comparison with a classical anthracycline-AraC consolidation regimen.

Definition: Extended description of the protocol, including information not already contained in other fields, such as comparison(s) studied.

APL is a specific type of acute myeloid leukemia (AML) characterized by its morphology (M3 or M3v in the FAB classification), t(15;17) translocation leading to PML-RARa fusion gene, and by a specific coagulopathy combining D.I.C., fibrinolysis and non specific proteolysis. ATRA can differentiate APL blasts in VITRO and in vivo. The combination of ATRA and anthracycline based chemotherapy yields CR rates greater than 90% in newly diagnosed APL. With early introduction of anthracycline AraC chemotherapy during induction treatment, and maintenance combining continuous 6MP and MTX to intermittent ATRA, the relapse risk in APL therefore now appears to be in the range of 10 to 15%.

Nevertheless, 5 to 10% of the patients do not achieve CR and 10% to 15% still relapse. Another subset of patients (5 to 7% in APL 93 trial including 17% of patients aged greater than 65 years) die in CR, from complications of the consolidation treatment phase, mainly from infection during chemotherapy induced aplasia. Failure to achieve CR with current treatment approaches is almost exclusively due to early death during induction treatment. Causes of death are predominantly bleeding, ATRA syndrome and less often infection. Early deaths predominate in elderly patients and patients with high WBC counts. Reducing the amount of chemotherapy administered to newly diagnosed APL patients diminishes this toxicity. The Spanish PETHEMA group reported results of two successive phase II trials in newly diagnosed APL with ATRA and chemotherapy with intercalating agents (idarubicin and mitoxantrone) without AraC followed by maintenance combining ATRA and low dose chemotherapy (LPA96 and LPA99 trials). Results appeared similar to those of the best arm of APL 93 trial, but with less toxicity and only 2 to 3 % death in CR were seen, including in elderly patients.

Arsenic trioxide (As2O3 or ATO) is an effective agent in relapsing or refractory APL, which induced 85% hematological and 79% molecular CR rates in a pivotal US study. The interest of ATO in the front-line therapy of newly-diagnosed APL has been strongly suggested in three studies which showed high complete remission rate, low incidence of relapse and limited toxicity.

In this study, patients will be stratified based on age (≤ 70 years and \> 70 years) and WBC count at diagnosis (WBC\<10.000/mm3 and \>10.000 /mm3).

-Patients aged 70 years or less with WBC\<10.000/mm3.

In this population (about 70 % of APL) the best treatment group of APL2000 trial (ATRA with early introduction of anthracycline-AraC chemotherapy but where Idarubicin will be substituted for Daunorubicin, followed by 2 anthracycline-AraC consolidation courses and maintenance combining continuous chemotherapy and intermittent ATRA) will be compared to the same regimen, but without AraC during consolidation courses which will be replaced by:

* either ATO
* or ATRA It is hoped that the investigational arms will further increase the event-free survival at 2 years, with reduced toxicity and without increasing the relapse rate by comparison with a classical anthracycline-AraC consolidation regimen.

  * Patients aged 70 years or less with WBC\>10.000/mm3 Patients ages 70 years or less with initial WBC counts \> 10000/mm3 (ie very high counts for APL), which represent about 20% of APL, remain at relatively high risk of relapse even with the current reference treatment. The main objective of the study will be to test the addition of ATO during consolidation courses to our current standard ATRA and chemotherapy regimen. Patients will receive the best treatment group of APL 2000 trial (but where Idarubicin will be substituted for Daunorubicin) with or without ATO during the 2 consolidation cycles.
  * Patients older than 70 years with WBC\<10.000 /mm3. Elderly patients with initial WBC ≤ 10000/m3 (about 8% of APL) and no contra indication to this treatment will receive a regimen with reduced cumulative dose of chemotherapy but addition of ATO during consolidation courses and during the first year of maintenance treatment. The main purpose of this non randomized part of the trial is to reduce the early death mortality and death in CR observed in elderly patients, without increasing the relapse rate.
  * Patients older than 70 years with WBC\>10.000 /mm3. Elderly patients with initial WBC \> 10000/m3 (about 2 to 3% of APL) and no contra indication to intensive regimen will receive the same regimen as those with low WBC but with moderate doses of Aracytine during the induction and during the first consolidation course. The main purpose of this non randomized part of the trial is to reduce the early death mortality and death in CR observed in elderly patients, without increasing the relapse rate.

Acute Promyelocytic Leukemia 2006 (APL)

A Randomized Trial Assessing the Role of Arsenic Trioxide and/or ATRA During Consolidation Course in Newly Diagnosed Acute Promyelocytic Leukemia (APL)

For Patients aged 70 years or less with WBC\<10.000/mm3, The primary end point

For patients older than 70 years with WBC\>10.000 /mm3, The primary end point will be EFS at 2 years from diagnosis

For Patients aged 70 years or less with WBC\<10.000/mm3 :

Kinetics of decrease of PML-RARA transcript level during and after consolidation course.

Side effects of the treatment, including treatment-related mortality and morbidity of consolidation treatment.

Days on antibiotics, transfusion requirement and nights spent in Hospital

For Patients aged 70 years or less with WBC\>10.000/mm3

event free survival at 2 years from CR achievement

For Patients older than 70 years with WBC\<10.000 /mm3

Kinetics of decrease of PML-RARA transcript level during and after

Side effects of the treatment, including mortality and morbidity of

For patients older than 70 years with WBC\>10.000 /mm3

Assistance Publique - Hôpitaux de Paris

Anti-Infective Agents

Anti-Inflammatory Agents

Antiemetics

Neuroprotective Agents

Gastrointestinal Agents

Cytarabine

Daunorubicin

Prednisolone

Methylprednisolone

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

Patients aged ≤ 60 years and with initial WBC ≤ 10000/mm3 Induction treatment

a) ATRA and chemotherapy ATRA 45 mg/m2/d until hematological CR first intensive chemotherapy course : DNR 60 mg/m2/d during 3 days AraC 200 mg/m2/d during 7 days

2) Consolidation treatment

1. First consolidation course (=2nd chemotherapy course) DNR 60 mg/m2/d d1-3 (intravenous bolus injection) AraC 200 mg/m2/d d1-7 (continuous infusion)
2. Second consolidation course AraC 1g/m2/12h d1-4 (1 hour infusion) Daunorubicin 45 mg/m2/d d1-3 (intravenous bolus injection) 3) Maintenance treatment

Consists of the combination of continuous low dose chemotherapy and intermittent ATRA, during 2 years

1. Continuous low dose chemotherapy
2. Intermittent ATRA

Patients aged ≤ 60 years and with initial WBC ≤ 10000/mm3 (Group B) Same treatment as Group A but without AraC.

1. First consolidation course (=2nd chemotherapy course) DNR 60 mg/m2/d d1-3 (intravenous bolus injection) AraC 200 mg/m2/d d1-7 (continuous infusion)
2. Second consolidation course AraC 1g/m2/12h d1-4 (1 hour infusion) Daunorubicin 45 mg/m2/d d1-3 (intravenous bolus injection)

CNS prophylaxis : consists of 5 intrathecal (IT) injections of MTX 15mg and AraC 50 mg (12 mg/m2 maximum 15 mg, and 30mg/m2, maximum 50 mg, respectively, in children) + depomedrol IT. I

3) Maintenance treatment

Patients aged \>60 years and initial WBC ≤ 10000/mm3 Induction treatment

a) ATRA and chemotherapy ATRA 45 mg/m2/d until hematological CR first intensive chemotherapy course : DNR 60 mg/m2/d during 3 days (intravenous bolus injection) NO ARA C DURING THIS FIRST COURSE

2) Consolidation treatment

1. First consolidation course DNR 60 mg/m2/d d1-3 AraC 100 mg/m2/d d1-5 G-CSF
2. Second consolidation course DNR45 mg/m2/d d1-3 AraC 100 mg/m2/d d1-5 G-CSF

   3) maintenance treatment: similar to other groups

Arac

Pierre Fenaux, MD

The first purpose of this randomized trial will be to compare the best treatment group of APL 93 trial (ATRA with early introduction of anthracycline-AraC chemotherapy, followed by 2 consolidation anthracycline-AraC courses and maintenance combining continuous chemotherapy and intermittent ATRA) to the same regimen, but without AraC. It is hoped that the investigational arm, with anthracycline alone chemotherapy (without AraC), will have reduced toxicity without increasing the incidence of relapse, by comparison with a classical induction/consolidation anthracycline-AraC regimen

Thus :

the main end point for this first randomization is relapse at 2 years secondary end points are : complete remission rate ; survival and event free survival at 2 years, and quality-adjusted survival (Q-TWiST).

2) Because patients with initial WBC counts \> 10000/mm3 (ie very high counts for APL) appear to remain at relatively high risk of relapse even with the current reference treatment, they will not be included in this trial that assesses the reduction of chemotherapy. On the contrary: i) they will all receive the standard chemotherapy (best treatment group of APL 93 trial);

Thus :

the main end point for this second randomization is relapse at 2 years secondary end points are : survival and event free survival at 2 years 3)Elderly patients with initial WBC ≤ 10000/m3 will receive consolidation chemotherapy without AraC during the first chemotherapy course, and reduced doses of AraC during the second and third course, followed by G-CSF.

All patients will receive induction treatment with ATRA and a first chemotherapy course, followed by two consolidation chemotherapy courses and maintenance with continuous low dose chemotherapy and intermittent ATRA. Initial stratification will be based on age and WBC count.

Patients aged 60 years with initial WBC 10 00 will all receive the reference AraC+ group (Group A ) (no randomization).

Patients with initial WBC \> 10000/mm3 will initially all be treated according to the AraC+ group.

Patients \> 60 years and with initial WBC ≤ 10000/mm3) will be only registered, without randomization (Group D) and will receive the reference AraC+ group ,but without AraC during the first chemotherapy course ,and with reduced doses of AraC during the second and third course, followed by G-CSF. .

A Randomized Trial Assessing the Roles of AraC in Newly Diagnosed APL Promyelocytic Leukemia (APL)

A Randomized Trial Assessing the Roles of AraC in Newly Diagnosed Acute Promyelocytic Leukemia (APL)

University Hospital, Lille

Groupe d'etude et de travail sur les leucemies aigues promyelocytaires

Centre Hospitalier Universitaire (CHU) of Lille, France.

Symptoms and General Pathology

Death

Martha Arellano, MD

Acute promyelocytic leukemia (APL) is a very rare type of leukemia. Because it is so rare, many doctors do not have experience treating it. APL has been shown to be curable most of the time. Unfortunately, some patients die early after they become sick with APL, sometimes even before starting treatment. The early period is from the time of diagnosis through the first treatments for the disease. This is approximately 30 days. Early deaths are often due to complications caused by of the effects of leukemia and the treatments of it. These complications may not be noticed quickly by doctors who don't have much experience with managing APL.

The purpose of this study is to collect information about the diagnosis and management of APL patients by review of their medical records. This information will be stored in a central database at Emory University. This data will be analyzed to discover the impact of increased physician knowledge of recommended management of APL. The goal is to reduce the events of early death of APL patients.

The investigators propose to collect data on patients with APL treated predominantly across the states of Georgia and South Carolina but will also extend it to cover patients from neighboring states. The treatment will be as per the treating physician and would be standard of care and no new drugs or changes to standard of care are being proposed in educating the treating physicians.

This is a multi-center study. At the lead sites, patients will sign the consent form and data will be collected at those respective sites. The sites outside of Emory are centers in the catchment area that treat leukemia. The lead investigators are available around the clock to co-manage the APL patients.

The objective of the study is to collect data to assess for improvement in mortality at the primary centers as well as at the local treatment centers. This change in mortality would depend on educating the community physicians and nursing staff and requires regular visits both by the physicians and the nurse coordinator. The community hematologists/oncologists in the catchment area will be educated by sending emails from investigators at 3 month intervals to inform them of the high early death rate associated with APL. In addition, a brief pamphlet will be mailed to them once every 3 months as a reminder. The lead investigators in each state will make presentations in regional meetings, visit practices, and also call local practices. In addition, a nurse coordinator will be instrumental in calling upon nursing staff in outlying hospitals in the catchment area to apprise them of early deaths in APL and also make them aware of the study and resources available. This will be done aggressively during the first 6 months prior to initiating the trial and will be continued during the three-year study period.

Impact of a Simplified Patient Care Strategy to Decrease Early Deaths in Acute Promyelocytic Leukemia (APL) by Maintaining a Database

Assessing the Impact of a Simplified Patient Care Strategy to Decrease Early Deaths In Acute Promyelocytic Leukemia (APL) By Maintaining A Database

Assessment of the severity and duration of coagulopathy, including presence or absence of clinically evident bleeding or bruising, and laboratory data including prothrombin time, activated partial thromboplastin time, international normalized ratio (INR), D-dimer, and fibrinogen

Correlation of mortality with the severity and duration of coagulopathy

Correlation of bleeding and infections and length of stay in hospital

Correlation of differentiation syndrome (dyspnea, unexplained fever, weight gain, peripheral edema, unexplained hypotension, acute renal failure \[ARF\], congestive heart failure \[CHF\], pleuropericardial effusions and interstitial pulmonary infiltrates) and length of hospital stay

Assessment of safety by grade 3 or 4 toxicity

Correlation of outcomes with time to initiation of treatment from diagnosis

Comparison of outcomes across different treatment centers.

The Leukemia and Lymphoma Society

Emory University

Principal Investigator

Analgesics

Mitoxantrone

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

all-trans retinoid acid

idarubicin

mitoxantrone

daunorubicin

cytarabine

Markus Schaich, MD

Silke Soucek

Gerhard Ehninger, MD

In AIDA 2000 therapy of acute promyelocytic leukemia (APL) is given in a risk-adapted manner. Risk factors are age and white-blood-cell (WBC)-count at diagnosis. Induction therapy is done with ATRA and idarubicin followed by postremission therapy with daunorubicin and mitoxantrone in age adapted dosages. Patients with an high WBC were additionally treated with cytarabine. Finally a two year period of maintenance therapy with 6-mercaptopurine, methotrexate and ATRA is performed.

AIDA2000 - Risk-Adapted Therapy for Patients With Acute Promyelocytic Leukemia

AIDA2000 - Risk-Adapted Therapy for Patients With Acute Promyelocytic Leukemia(APL)

Technische Universität Dresden

Prof. Dr. Gerhard Ehninger

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Methotrexate

Mercaptopurine

Tretinoin

Keratolytic Agents

Patients 65 years of age with a WBC count less than 5,000 were randomized to receive the reference ATRA treatment of our previous trial (APL91 trial), ie, 45 mg/m2/d ATRA followed by CT or ATRA plus CT (ATRA+CT). In the ATRA followed byCT group, patients received 45 mg/m2/d ATRA orally until CR, with a maximum of 90 days. After CR achievement, they received a course of 60 mg/m2/d daunorubicin (DNR) for 3 days and 200 mg/m2/d AraC for 7 days (course I). However, course I was added to ATRA if the WBC count was increased to greater than 6,000, 10,000, or 15,000 by day 5, 10, and 15 of ATRA treatment, respectively, because, from our experience, patients were at risk of ATRA syndrome above those thresholds.

Patients randomized to the ATRA+CT group received the same combination of ATRA and CT, with course I of CT starting on day 3 of ATRA treatment. This 48-hour interval before onset of CT was based on our previous report, because it allowed correction of coagulopathy.

Patients with a WBC count greater than 5,000 at presentation (irrespective of their age) and patients 66 to 75 years of age with a WBC count 5,000 were not randomized but received ATRA plus CT course I from day 1 (high WBC group) and the same schedule as in the ATRA-\>CT group (elderly group), respectively.

continuous CT with 6 mercaptopurine (90 mg/m2/d, orally) and methotrexate (15 mg/m2/wk, orally) as maintenance

continuous CT with 6 mercaptopurine (90 mg/m2/d, orally) and methotrexate (15 mg/m2/wk, orally) AND ATRA as maintenance

patients were randomized both to receive or not receive intermittent ATRA (45 mg/m2/d, 15 days every 3 months) and to receive or not receive continuous CT with 6 mercaptopurine (90 mg/m2/d, orally) and methotrexate (15 mg/m2/wk, orally), according to a 2-by-2 factorial design stratified on the initial induction treatment group

ATRA and or Chemo as maintenance

pierre fenaux, mD

Objectives of the trial were to assess the optimal timing of chemotherapy with or after ATRA and the role of maintenance therapy.

Induction treatment was stratified by age and initial WBC count. Patients ≤65 years of age with a WBC count less than 5,000/µL were randomized to receive the reference ATRA treatment of our previous trial (APL91 trial) {Fenaux, 1993 #2088}, ie, 45 mg/m2/d ATRA followed by CT (ATRA→CT group) or ATRA plus CT (ATRA+CT). In the ATRA→CT group, patients received 45 mg/m2/d ATRA orally until CR, with a maximum of 90 days. After CR achievement, they received a course of 60 mg/m2/d daunorubicin (DNR) for 3 days and 200 mg/m2/d AraC for 7 days (course I). However, course I was added to ATRA if the WBC count was increased to greater than 6,000/µL, 10,000/µL, or 15,000/µL by day 5, 10, and 15 of ATRA treatment, respectively, be-cause, from our experience, patients were at risk of ATRA syndrome above those thresholds{de Botton, 2003 #1127; De Botton, 1998 #1604}. Patients randomized to the ATRA+CT group received the same combination of ATRA and CT, with course I of CT starting on day 3 of ATRA treatment.

Patients with a WBC count greater than 5,000/µL at presentation (irrespective of their age) and patients 66 to 75 years of age with a WBC count ≤ 5,000/µL were not ran-domized but received ATRA plus CT course I from day 1 (high WBC group) and the same schedule as in the ATRA→CT group (elderly group), respectively.

Treatment of coagulopathy during the induction phase was based on platelet support to maintain the platelet count at a level greater than 50,000 /µL until the disappea-rance of coagulopathy. The use of heparin, tranexamic acid, fresh frozen plasma, and fibrinogen transfusions was optional.

CR patients received 2 CT consolidation courses, including course II (identical to course I) and course III, consisting of 45 mg/m2/d DNR for 3 days and 1 g/m2 AraC every 12 hours for 4 days. The elderly group only received course II.

Three to 4 weeks after hematological recovery from this consolidation CT, patients who were still in CR were randomized both to receive or not receive intermittent ATRA (45 mg/m2/d, 15 days every 3 months) and to receive or not receive continuous CT with 6 mercaptopurine (90 mg/m2/d, orally) and methotrexate (15 mg/m2/wk, oral-ly), according to a 2-by-2 factorial design stratified on the initial induction treatment group. Maintenance treatment was scheduled for 2 years. Randomizations for induc-tion and maintenance, stratified on center, were performed through a centralized tele-phone assignment procedure.

APL93: Timing of CxT and Role of Maintenance

Assessment of the Optimal Timing of Chemotherapy With or After ATRA and the Role of Maintenance

DRC lille, France

DRC Lille

Syndrome

Preleukemia

Myelodysplastic Syndromes

Bone Marrow Diseases

Precancerous Conditions

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Sorafenib

Vorinostat

Protein Kinase Inhibitors

Histone Deacetylase Inhibitors

This is a single-arm, non-randomized feasibility and safety Phase I trial of a combination of Sorafenib and Vorinostat, both administered orally.

Patients will be entered in successive cohorts. The first cohort will receive Sorafenib at 400 mg bid (800 mg daily) and Vorinostat at 100 mg bid (200 mg daily).

Sorafenib-Vorinostat

Hamid Sayar, MD

The purpose of this study is to test the safety of sorafenib and vorinostat when given together to see what effects (good and bad) it has on the patient and their acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). This study is also being done to find the highest dose of sorafenib and vorinostat that can be given together without causing severe side effects.

Combination of Sorafenib and Vorinostat in Poor-risk Acute Myelogenous Leukemia (AML) and High Risk Myelodysplastic Syndrome (MDS)

Phase I, Open-label, Dose-escalation Study of the Combination of Sorafenib and Vorinostat in Poor-risk Acute Myelogenous Leukemia (AML) and High Risk Myelodysplastic Syndrome (MDS)

Bayer

Indiana University School of Medicine

Immune System Diseases

Nervous System Diseases

Diseases and Abnormalities at or Before Birth

Musculoskeletal Diseases

Skin and Connective Tissue Diseases

Wounds and Injuries

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Sarcoma

Lymphoma

Neurofibromatoses

Neurofibromatosis 1

Neurofibroma

Neurofibroma, Plexiform

Giant Cell Tumors

Giant Cell Tumor of Tendon Sheath

Neoplasms, Connective and Soft Tissue

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Nerve Sheath Neoplasms

Neoplasms, Nerve Tissue

Neoplastic Syndromes, Hereditary

Neurocutaneous Syndromes

Heredodegenerative Disorders, Nervous System

Neurodegenerative Diseases

Genetic Diseases, Inborn

Peripheral Nervous System Diseases

Neuromuscular Diseases

Nervous System Neoplasms

Peripheral Nervous System Neoplasms

Neoplasms, Connective Tissue

Synovitis

Joint Diseases

Tendinopathy

Muscular Diseases

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Soft Tissue Sarcoma

Lymphosarcoma

Neurofibromatosis

Neurofibromatosis Type 1

Pigmented Villonodular Synovitis

TURALIO(R)

Elaine W Thomas

Rosandra N Kaplan, M.D.

Background:

- Some people with cancer have solid tumors. Others have refractory leukemia. This may not go away after treatment. Researchers want to see if a drug called TURALIO(R) can shrink tumors or stop them from growing.

Objectives:

- To find the highest safe dose and side effects of TURALIO(R). To see if it helps treat certain types of cancer.

Eligibility:

- People ages 3-35 with a solid tumor or leukemia that has returned or not responded to cancer therapies.

Design:

* Participants will be screened with:
* Medical history
* Physical exam
* Blood and urine tests
* Heart tests
* Scans or other tests of the tumor
* Participants will take TURALIO(R) as a capsule once daily for a 28-day cycle. They can do this for up to 2 years.
* During the study, participants will have many tests and procedures. They include repeats of the screening tests. Participants will keep a diary of symptoms.
* Participants with solid tumors will have scans or x-rays.
* Participants with leukemia will have blood tests. They may have a bone marrow sample taken.
* Some participants may have a biopsy.
* When finished taking TURALIO(R), participants will have follow-up visits. They will repeat the screening tests and note side effects.

Background

* Traditional therapeutic approaches to pediatric cancer have focused on cytotoxic agents and, more recently, targeted inhibition of cellular signaling pathways through the use of small molecule kinase inhibitors. Despite these interventions, significant numbers of pediatric cancer patients develop recurrent and resistant disease. Targeting the tumor microenvironment is a promising but incompletely explored strategy for the treatment of pediatric cancer and non-cancer tumors.
* This trial will begin to explore the disruption of the interaction between neoplastic cells and the myeloid component of the tumor microenvironment as a treatment strategy for pediatric cancers and neurofibromatosis type 1 (NF1) related plexiform neurofibromas (PN) and malignant peripheral nerve sheath tumor (MPNST).
* TURALIO(R) is an orally available small molecule inhibitor of class III protein tyrosine kinases including Kit, CSF1R (colony stimulating factor 1 receptor)/Fms (Feline McDonough Sarcoma), and oncogenic Flt3 (Fms like tyrosine kinase).

Primary Objectives

-Evaluate the safety and tolerability of TURALIO(R) and determine a recommended phase II dose of TURALIO(R) in pediatric patients with refractory solid tumors including NF1 MPNST and brain tumors or refractory leukemias, limited to acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL).

Eligibility

-\>= 3 and \<= 35 years of age

* Recurrent or refractory solid tumors including primary neoplasms of the central nervous system and patients with NF1 and MPNST, or refractory leukemias (AML or ALL).
* Subjects must have adequate performance status, be able to swallow tablets, may not be pregnant or breastfeeding, and have adequate major organ function. Subjects with history of severe or uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic cardiovascular or pulmonary disease, or history of prolonged QT syndrome will be excluded.

Design

* Using a rolling-six phase I design with 2-6 subjects per dose level and standard definitions of MTD (during cycle 1) and DLT.
* TURALIO(R) will be administered orally (125 mg capsules) once daily on a continuous basis for cycles of 28 days without a rest period between cycles. Patients must be able to swallow intact capsules. Dosing will be based on body surface area (BSA), and the total weekly dose will be rounded to within 10% of calculated dose using a dosing nomogram.
* At the MTD, the recommended phase II dose level will be expanded to up to 12 patients with attempts made to enroll at least 3 patients with refractory solid tumors and 3 patients with refractory acute leukemia (ALL and AML) to gain more experience with the toxicities and pharmacokinetics of TURALIO(R) in these disease cohorts. Attempts will be made to enroll equal numbers of patients between the ages of 3 and 12 years and over 12 years of age to gain pharmacokinetic and safety data over a broad age range.

Phase I Trial of TURALIO(R) (Pexidartinib, PLX3397) in Children and Young Adults With Refractory Leukemias and Refractory Solid Tumors Including Neurofibromatosis Type 1 (NF1) Associated Plexiform Neurofibromas (PN) and Tenosynovial Giant Cell Tumor ...

Phase I Trial of TURALIO (Pexidartinib, PLX3397) in Children and Young Adults With Refractory Leukemias and Refractory Solid Tumors Including Neurofibromatosis Type 1 (NF1) Associated Plexiform Neurofibromas (PN) and Tenosynovial Giant Cell Tumor (TGCT)

.All IPD recorded in the medical record will be shared with intramural investigators upon request. All collected IPD will be shared with collaborators under the terms of collaborative agreements.

Evaluate the safety and tolerability of TURALIO(R)

Evaluate biologic activity and extended tolerability of TURALIO(R)

Preliminarily determine the antitumor activity within the confines of a phase 1 study for recurrent or refractory pediatric solid tumors and leukemia (AML and ALL)

Evaluate patient reported and functional outcomes

Determine effect of TURALIO(R) on circulating biomarkers

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Acute Promyelocytic Leukemia 2006 (APL)	NCT00378365	Leukemia, Promy...	Arsenic trioxid... ATRA	18 Years -	Assistance Publique - Hôpitaux de Paris
A Randomized Trial Assessing the Roles of AraC in Newly Diagnosed APL Promyelocytic Leukemia (APL)	NCT00591526	Leukemia, Promy...	Arac	-	Groupe d'etude et de travail sur les leucemies aigues promyelocytaires
Impact of a Simplified Patient Care Strategy to Decrease Early Deaths in Acute Promyelocytic Leukemia (APL) by Maintaining a Database	NCT02309333	Leukemia, Promy...		-	Emory University
AIDA2000 - Risk-Adapted Therapy for Patients With Acute Promyelocytic Leukemia	NCT00180128	Leukemia, Promy...	all-trans retin... idarubicin mitoxantrone daunorubicin cytarabine	16 Years -	Technische Universität Dresden
APL93: Timing of CxT and Role of Maintenance	NCT00599937	Leukemia, Promy...	ATRA ATRA and or Che...	-	Groupe d'etude et de travail sur les leucemies aigues promyelocytaires
Acute Promyelocytic Leukemia 2006 (APL)	NCT00378365	Leukemia, Promy...	Arsenic trioxid... ATRA	18 Years -	Assistance Publique - Hôpitaux de Paris
Combination of Sorafenib and Vorinostat in Poor-risk Acute Myelogenous Leukemia (AML) and High Risk Myelodysplastic Syndrome (MDS)	NCT00875745	Leukemia, Myelo... Leukemia, Promy... Myelodysplastic...	Sorafenib-Vorin...	18 Years -	Indiana University
A Randomized Trial Assessing the Roles of AraC in Newly Diagnosed APL Promyelocytic Leukemia (APL)	NCT00591526	Leukemia, Promy...	Arac	-	Groupe d'etude et de travail sur les leucemies aigues promyelocytaires
Phase I Trial of TURALIO(R) (Pexidartinib, PLX3397) in Children and Young Adults With Refractory Leukemias and Refractory Solid Tumors Including Neurofibromatosis Type 1 (NF1) Associated Plexiform Neurofibromas (PN) and Tenosynovial Giant Cell Tumor ...	NCT02390752	Neurofibroma, P... Precursor Cell ... Leukemia, Promy... Sarcoma	TURALIO(R)	3 Years - 35 Years	National Institutes of Health Clinical Center (CC)
Impact of a Simplified Patient Care Strategy to Decrease Early Deaths in Acute Promyelocytic Leukemia (APL) by Maintaining a Database	NCT02309333	Leukemia, Promy...		-	Emory University

Spots Global Cancer Trial Database for leukemia, promyelocytic, acute