Symptoms and General Pathology

All Conditions

Neoplasms

Immune System Diseases

Blood and Lymph Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Syndrome

Mastocytosis

Leukemia

Leukemia, Myeloid

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Hematologic Neoplasms

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Philadelphia Chromosome

Mastocytosis, Systemic

Hypereosinophilic Syndrome

Blast Crisis

Lymphoma

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Translocation, Genetic

Chromosome Aberrations

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Mast Cell Activation Disorders

Eosinophilia

Leukocyte Disorders

Myeloid Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Graft Versus Host Disease

Chronic Myeloid Leukemia

Acute Graft Versus Host Disease

Systemic Mastocytosis

Lymphosarcoma

Chronic Myeloproliferative Disorders

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Nilotinib

Imatinib Mesylate

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Imatinib-resistant / intolerant PH+ CML-CP patients

Imatinib-resistant / intolerant PH+ CML-AP patients

Novartis Pharmaceuticlas

The purpose of this trial is to assess the efficacy, safety, tolerability, biologic activity, and pharmacokinetics of AMN107 in six groups of patients with one of the following conditions:

Relapsed/refractory Ph+ Acute lymphoblastic leukemia (ALL) (arm 1)

Group A - Imatinib failure only (arms 2, 3 and 4)

* imatinib-resistant or intolerant CML - Chronic Phase (CP)
* imatinib-resistant or intolerant CML - Accelerated Phase (AP)
* imatinib-resistant or intolerant CML - Blast Crisis (BC)

Group B - Imatinib and other TKI failure (arms 2, 3 and 4)

* imatinib-resistant or intolerant CML - Chronic Phase (CP)
* imatinib-resistant or intolerant CML - Accelerated Phase (AP)
* imatinib-resistant or intolerant CML - Blast Crisis (BC)

Hypereosinophilic syndrome/chronic eosinophilic leukemia (HES/CEL) (arm 5)

Systemic mastocytosis (Sm) (arm 6)

A Study of Oral AMN107 in Adults With Chronic Myelogenous Leukemia (CML) or Other Hematologic Malignancies

A Phase IA/II Multicenter, Dose-escalation Study of Oral AMN107 on a Continuous Daily Dosing Schedule in Adult Patients With Imatinib-resistant/Intolerant CML in Chronic or Accelerated Phase or Blast Crisis, Relapsed/Refractory Ph+ ALL, and Other Hematologic Malignancies.

Major Cytogenetic Response (MCyR) is defined as Complete Cytogenetic Response (CCyR: 0% Ph-chromosome-positive cells in metaphase in bone marrow) or Partial Cytogenetic Response (PCyR: 1-35% Ph-chromosome-positive cells in metaphase in bone marrow).

Hematologic response is defined as the percentage of participants in complete hematologic response (defined as the following present for at least 4 weeks: WBC count \<10 x 109/L, Platelet count \<450 x 109/L, Basophils \<5%, No blasts and promyelocytes in peripheral blood, Myelocytes + metamyelocytes \< 5% in peripheral blood, No evidence of extramedullary disease, including spleen and liver).

Hematological response was a primary outcome measure for Arm CML-AP with prior imatinib only.

Cytogenetic responses (CyRs) in CML are based on the percentage of Ph+ metaphases in bone marrow; a value of 0% Ph+ metaphases defines a complete cytogenetic response (CCyR) and \>0% to 35% defines a major cytogenetic response (MCyR). Achievement of CCyR is associated with a significant survival advantage in participants with CML-CP. MCyR was categorized as either CCyR or partial cytogenetic response (PCyR).

A Complete Hematologic Response (CHR) is obtained when all the following criteria are met: WBC ≤ institutional ULN; platelets ≤ 450,000/mm3; ≤20% basophils in peripheral blood; no blasts or promyelocytes in PB cells; \< 5% myelocytes plus metamyelocytes in PB cells; no extra-medullary involvement including no hepatomegaly or splenomegaly.

MMR was defined for participants who demonstrated a reduction in BCR-ABL/control gene % transcripts to ≤0.1% based on international scale. The control gene used may have been either BCR or ABL.

Time to Progression was defined as the time from the start of nilotinib to the earliest date of Disease Progression (PD), discontinuation due to PD or death.

Disease progression was defined as an increase in the number of circulating leukemic cells via cytogenetic assessment using real-time quantitative reverse transcriptase polymerase chain reaction (PCR).

OS was calculated for all participants as the time between the start of nilotinib and death. Participants were followed for survival after discontinuation, every 3 months, and were included in the analysis of OS. Censoring was at the date of the last contact for discontinued participants and followed up for survival.

Adverse events (AEs) were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events (SAEs) were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards.

Novartis Pharmaceuticals

Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.

Adult participants PH+ CML-CP without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).

CML-CP With Prior Imatinib Only

Adult participants Ph+ CML-AP without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).

CML-AP With Prior Imatinib Only

Adult participants Ph+ CML-CP in addition to prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).

CML-CP

Adult participants PH+ CML-AP without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).

Adult participants PH+ CML-CP in addition to prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).

Total

<35 years

≥35 to <55 years

≥55 to <65 years

≥65 years

Age, Customized

Sex: Female, Male

Study Director

Adult participants PH+ CML-AP (Accelerated Phase Chronic Myeloid Leukemia) without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).

Full Analysis Set (FAS): All participants who received at least one dose of study medication

Number of Participants With Major Cytogenetic Response (MCyR)

Full Analysis Set (FAS): All participants who received at least one dose of study medication.

Number of Participants Confirmed Overall Hematological Response (Phase II)

Number of Participants With Overall Major Cytogenetic Responses (Phase II)

Number of Participants With Complete Hematologic Response (Phase II)

Full Analysis Set (FAS): All participants who received at least one dose of study medication.

Major molecular response was not an efficacy variable for participants who received the CML-CP with prior imatinib and other TKI (Group B E8)

Participants With (MMR) Major Molecular Response (Phase II)

Full Analysis Set (FAS): All participants who received at least one dose of study medication.

Time to progression was not an efficacy variable for participants who received the CML-CP with prior imatinib and other TKI (Group B E8).

Time to Progression (TTP) (Phase II)

Overall Survival (OS) (Phase II)

Serious Adverse Events

Adverse Events

Adult participants PH+ CML-CP ( Chronic Phase Chronic Myeloid Leukemia) without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).

Number of Participants With Adverse Events and Serious Adverse Events to Evaluate Long Term Safety

Overall Study

Leukemia, Mast-Cell

Analgesics

Denileukin diftitox

Interleukin-2

Analgesics, Non-Narcotic

Ontak administered intravenously on Days 1-5 at the dose of 9 µg/kg/day, with a rest period from Days 6-21.

9 µg/kg by vein Days 1-5 of a 21 day cycle.

Ontak (Denileukin Diftitox)

Srdan Verstovsek, MD

Primary Objective:

1. To assess the response rate of ONTAK in Systemic Mastocytosis (SM) patients.

Secondary Objectives:

1. To assess the safety of ONTAK in SM patients.
2. To evaluate the time to progression and duration of response following treatment with ONTAK.

Denileukin diftitox has been used for the treatment of a variety of disorders, in particular, malignant lymphoma, another blood-related disease. Denileukin diftitox is believed to be able to specifically attach to and kill malignant mast cells.

Before you can start treatment on this study, you will have what are called "screening tests". These tests will help the doctor decide if you are eligible to take part in the study. You will have blood (around 2 teaspoons) and bone marrow samples collected. To collect a bone marrow sample, an area of the hip bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle. These samples will be used for tests to confirm the diagnosis of the disease. Women who are able to have children must have a negative blood pregnancy test.

If you are found to be eligible, you will receive denileukin diftitox as an injection by vein once a day for 5 days in a row. This will be repeated every 3 weeks (1 cycle). You will receive treatment on an outpatient basis. Treatment will continue as long as there is evidence that therapy is affecting the disease and is beneficial to you. If the disease gets worse or you experience any intolerable side effects, you will be taken off the study and your doctor will discuss other treatment options with you.

During treatment you will have blood (around 1 teaspoon) collected twice during every 3-week period. You will also have bone marrow samples collected every 3 months during the treatment.

After the end of treatment, blood and bone marrow samples will be collected every 3 months until the disease gets worse or you start a different therapy. The blood and bone marrow samples will be used to look at response to therapy.

This is an investigational study. Denileukin diftitox has been approved by the FDA for the treatment of skin T-cell lymphoma and is commercially available. The use of denileukin diftitox in this study is investigational. You will be provided denileukin diftitox free of charge. Up to 25 participants will take part in this study. All be enrolled at M. D. Anderson.

Ontak (Denileukin Diftitox) in Patients With Systemic Mastocytosis (SM)

ONTAK (Denileukin Diftitox) in Patients With Systemic Mastocytosis

Bone marrow samples used to look at response to therapy collected every 3 months until disease progression or different therapy started. Clinical efficacy assessed as objective response (major and partial response) for responding patients analyzed by the Kaplan-Meier method.

M.D. Anderson Cancer Center

Obatoclax

30 mg by vein over 3 hours Days 1-3, 14-day cycle

30 mg given by vein over 3 hours on Days 1-3 of each 14-day study cycle.

Obatoclax Mesylate

The goal of this clinical research study is to learn if obatoclax mesylate can help to control systemic mastocytosis. The safety of this drug will also be tested.

The Study Drug:

Obatoclax mesylate is designed to block the growth of malignant mast cells. This may cause cancer cells to die.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive obatoclax mesylate through a peripheral intravenous catheter (a needle in the vein of your arm). The drug will be given over 3 hours each day on Days 1-3 of each 14-day study cycle.

If the study doctor thinks it is needed, you might receive the study drug though a silicone-based central venous catheter (CVC). A central venous catheter is a sterile flexible tube that will be placed into a large vein while you are under local anesthesia. Some catheters cannot be used with the study drug. If you already have one of these catheters in your body, it may need to be replaced before you can begin receiving the study drug. You will sign a separate consent that will describe the procedure and its risks in detail.

Study Visits:

One (1) time during each study cycle, the following tests and procedures will be performed:

* You will be asked about any side effects you may be having and about any other drugs you may be taking.
* Blood (about 2 tablespoons) will be drawn for routine tests.

Every 3 months while you are taking the study drug, you will have a bone marrow biopsy/aspirate to check the status of the disease.

Length of Study:

You will be able to continue receiving the study drug for as long as you are benefitting. You will be taken off study if you have intolerable side effects or if the disease gets worse.

Follow-Up:

Three months after your last dose of study drug, your doctor will call you to ask you how you are feeling. This call should take about 10 minutes.

Additional Information:

* You must tell your doctor about any drug allergies you may have.
* You must tell your doctor about how much alcohol you consume and about any other drugs you may be taking, including vitamins, herbal remedies, and over-the-counter, prescription, and/or illegal drugs. Some of these will interact with the study drug.
* You must arrange to have someone drive you home after each treatment. You must not drive or operate machinery (including kitchen appliances) after you have received the study drug until any possible side effects have gone away.
* If you feel you any side effects or symptoms while you are on study, you must contact your doctor right away.

This is an investigational study. Obatoclax mesylate is not FDA approved or commercially available. At this time, obatoclax mesylate is only being used in research.

Up to 25 patients will take part in this study. All will be enrolled at M. D. Anderson.

Obatoclax for Systemic Mastocytosis

Evaluation of Obatoclax Mesylate as Therapy for Patients With Systemic Mastocytosis

Response rate is defined as number of participants with objective response divided by number of participants evaluated. Objective response is complete response and partial response where 'complete response' constitutes total elimination of a symptom or sign of the disease; 'partial response' constitutes at least 50% improvement in a symptom or sign of the disease. Objective response definitions of response evaluated following guidelines proposed by Valent et al. (International working group consensus criteria).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Oral AMN107 in Adults With Chronic Myelogenous Leukemia (CML) or Other Hematologic Malignancies	NCT00109707	Chronic Myeloge... Acute Lymphobla... Hypereosinophil... Systemic Mastoc...	Nilotinib	18 Years -	Novartis
Ontak (Denileukin Diftitox) in Patients With Systemic Mastocytosis (SM)	NCT00493129	Leukemia Systemic Mastoc...	Ontak (Denileuk...	-	M.D. Anderson Cancer Center
Obatoclax for Systemic Mastocytosis	NCT00918931	Leukemia Systemic Mastoc...	Obatoclax Mesyl...	18 Years -	M.D. Anderson Cancer Center
Ontak (Denileukin Diftitox) in Patients With Systemic Mastocytosis (SM)	NCT00493129	Leukemia Systemic Mastoc...	Ontak (Denileuk...	-	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for sm

Every month we try and update this database with for sm 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.

Spots Global Cancer Trial Database for sm

Every month we try and update this database with for sm 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.

Every month we try and update this database with for sm 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.