Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Lawrence Druhan, PH.D.

The purpose of this study is to obtain high quality specimens for molecular studies for the identification and characterization of genetic mutations involved in the pathogenesis of familial myeloid malignancies. Specimens obtained will be de-identified, linked to basic clinical data, and sent to Washington University (Division of Oncology, St. Louis, MO) for molecular analyses. Some specimens sent to Washington University may also be used for quality control analyses.

This is a specimen collection study for patients receiving standard of care treatment for AML. Specimens collected will be 1) bone marrow biopsy and aspiration, 2) peripheral blood, 3) skin punch biopsy, and 4) oral rinse. Collection of these specimens will be at timepoints determined by the patient's standard of care and their physician Investigator.

LCI-HEM-SPEC-001: Tissue Collection for Genetic Analysis of Acute Myelogenous Leukemia

LCI-HEM-SPEC-001: Tissue Collection for Familial Acute Myelogenous Leukemia Genetic Analysis

Wake Forest University Health Sciences

Immune System Diseases

Symptoms and General Pathology

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Neoplasm, Residual

Lymphoma

Neoplastic Processes

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Lymphosarcoma

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Micronutrients

Hematinics

Vitamins

Cytarabine

Fludarabine

Fludarabine phosphate

Methotrexate

Vidarabine

Clofarabine

Antimetabolites

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Immunosuppressive Agents

Immunologic Factors

Antiviral Agents

Folinic Acid

Folate

Vitamin B9

A maximum of two courses of the following regimen will be administered.

* Clofarabine: 20 mg/m2/day intravenously (IV) over 2 hours (given at hours 0 to 2) on days 1 through 5.
* Cytarabine intravenous: 1 gram/m2/day intravenously (IV) over 2 hours to be given 4 hours after the initiation of clofarabine on days 1 through 5.
* Methotrexate: to be given intrathecally (IT) to all acute lymphoblastic leukemia (ALL) patients on day 1 at the dose defined by age.
* Intrathecal (IT) cytarabine: is optional for acute myelogenous leukemia (AML) patients.

20 mg/m2/day intravenously (IV) over 2 hours (given at hours 0 to 2) on days 1 through 5.

1 gram/m2/day intravenously (IV) over 2 hours to be given 4 hours after the initiation of clofarabine on days 1 through 5.

Cytarabine intravenous

Methotrexate to be given intrathecally (IT) to all acute lymphoblastic leukemia (ALL) patients on day 1 at the dose defined by age below:

* 8 mg for patients age 1-1.99
* 10 mg for patients age 2-2.99
* 12 mg for patients 3-8.99 years of age
* 15 mg for patients \>9 years of age

Intrathecal (IT) cytarabine is optional for acute myelogenous leukemia (AML) patients.

If intrathecal cytarabine is to be given, it must be given at least 72 hours but not more than 7 days prior to the initiation of intravenous cytarabine.

Dose should be given according to age as defined below:

* 30 mg for patients age 1-1.99
* 50 mg for patients age 2-2.99
* 70 mg for patients \>3 years of age

Intrathecal (IT) Cytarabine

Blythe Thomson, MD

This study will test the ability of clofarabine + cytarabine to eliminate minimal residual disease (MRD) in acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) patients whose bone marrows exhibit complete remission by morphology. The toxicity profile of this regimen will be evaluated in addition to toxicity experienced by patients who proceed to stem cell transplant. Overall length of remission will also be collected.

Recent studies have demonstrated that even low levels of minimum residual disease (MRD) (\>0.01% abnormal blasts) after aggressive re-induction therapy indicate a relatively poor outcome in relapsed acute lymphoblastic leukemia (ALL) patients, including those who proceed to allogeneic stem cell transplant (alloSCT). A similarly poor prognosis was seen in pediatric acute myelogenous leukemia patients with sub-morphologic disease prior to alloSCT. Studies to identify therapies that can eliminate persistent leukemia, have low toxicity profiles and can serve as a bridge to transplant are needed.

This study will test the ability of clofarabine + cytarabine to eliminate minimal residual disease (MRD) in acute myelogenous leukemia and acute lymphoblastic leukemia patients whose bone marrows exhibit complete remission by morphology. The toxicity profile of this regimen will be evaluated in addition to toxicity experienced by patients who proceed to stem cell transplant. Overall length of remission will also be collected.

Clofarabine With Cytarabine for Patients With Minimal Residual Disease Positive Leukemia

Clofarabine With Cytarabine for MRD Positive Leukemia

To be assessed in acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) patients whose bone marrows exhibit complete remission by morphology. Patient's bone marrow will be evaluated for the amount of minimal residual disease (MRD) present after treatment on courses 1 and 2.

Treatment related toxicities that preclude proceeding to HSCT by day 56 of the treatment course.

After the patient completes therapy on this protocol, data will continue to be collected regarding whether the patient proceeded to HCT. Toxicity and adverse event information will be collected.

Genzyme, a Sanofi Company

Therapeutic Advances in Childhood Leukemia Consortium

The definition of AE and SAE used to collect adverse event information does not differ from the clinicaltrials.gov definitions.

Clofarabine, Cytarabine, Methotrexate

See detailed description in Interventions section.

Single Arm

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

The study only enrolled two patients and closed early due to low accrual.

Peggy Romano, BA, CCRP

Study was closed prematurely and none of the patients treated were eligible for analysis of disease response.

Minimal Residual Disease (MRD)

All patients treated on Treatment Course 1.

Number of Patients With Dose-Limiting Toxicity (DLT)

None of the patients treated on Treatment Course 1 proceeded to HCT. 1 patient upon completion of Treatment Course 1 proceeded with Bone Marrow Transplant and 1 patient was removed early from protocol treatment during Course 1 due to progressive disease.

Occurrence of Toxicity During Hematopoietic Cell Transplant (HCT) for Patients Who Achieve Remission and Proceed to Transplant

Treatment Course 1

Treatment Course 2

Syndrome

Preleukemia

Myelodysplastic Syndromes

Bone Marrow Diseases

Precancerous Conditions

Combretastatin

Tubulin Modulators

Antimitotic Agents

Dosing of OXi4503 will be an intravenous infusion (IV) over 10 minutes on Days 1, 8, 15, and 22 of each 28 day cycle.

Two safety cohorts treating two (2) patients at a dose of 2.5 mg/m2 followed by two patients at 3.75 mg/m2 will be completed prior to beginning at the dose level of 5 mg/m2.

Dosing of OXi4503 will be an intravenous infusion (IV) over 10 minutes on Days 1, 8, 15, and 22 of each 28 day cycle.

Dose escalations and de-escalations of 25% will be made until the maximum tolerated dose is reached.

Number of cycles: After Cycle 1, subjects who achieve stable disease (SD) or greater response may continue to receive additional cycles of treatment until either disease progression (defined as greater than 25% increase in leukemia myeloblasts in the bone marrow compared to baseline examination) or unacceptable toxicity due to the investigational agent.

OXi4503

Christopher R. Cogle, MD

This study is intended to determine the safety and maximum tolerated dose of a drug, OXi4503 (combretastatin A1 diphosphate, CA1P, OXiGENE), in patients with relapsed and refractory AML and MDS.

Despite initial disease remissions with cytotoxic chemotherapies, patients with AML and MDS often relapse and die of their disease. Novel strategies for targeting dependent pathways are needed. AML and MDS depend on blood vessels for survival and proliferation. OXi4503 is a novel microtubule targeting agent that selectively destroys cancer-associated blood vessels, induces cancer cell apoptosis via an ortho-quinone moiety and results in significant regressions of solid tumors. OXi4503 is currently being tested in phase I clinical trials of advanced solid tumors. In preclinical studies with human AML, OXi4503 was cytotoxic to leukemia cells, decreased size of chloromas, regressed leukemic cell engraftment in bone marrow and brought about phenotypic and molecular remissions. Given these results, we hypothesize that OXi4503 has disease remitting effects in myeloid malignancies such as AML and MDS. Before evaluating efficacy, safety and maximum tolerated dose of OXi4503 will be defined in AML and MDS patients. In addition, assessments of pharmacokinetic (PK) and pharmacokinetic (PD) parameters will be made, and relationships between dose and biologic activity will be defined. Results from this trial will provide new clinical data and biologic insight regarding the effects of OXi4503 in AML and MDS, and will serve as the basis for future efficacy trials.

A Phase I Clinical Trial of OXi4503 for Relapsed and Refractory AML and MDS

A Phase I Clinical Trial of OXi4503 for Relapsed and Refractory Acute Myelogenous Leukemia (AML) and Myelodysplastic Syndromes (MDS)

The Leukemia and Lymphoma Society

University of Florida

Graft vs Host Disease

Leukemia, Myelomonocytic, Juvenile

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Myeloproliferative Disorders

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Homologous Wasting Disease

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Chronic Myeloproliferative Disorders

Anticonvulsants

Antiemetics

Central Nervous System Depressants

Psychotropic Drugs

Gastrointestinal Agents

Etoposide

Cyclophosphamide

Lorazepam

Etoposide phosphate

Busulfan

Total Body Irradiation (TBI) 1200 cGy will be given on days -8,-7,-6 and -5 in eight sessions, delivering 150cGy in each session.

Etoposide 1000 mg/m2 as a 24 hour continuous infusion started on day -4.

Cyclophosphamide 60 mg/kg/day IV given over 1 hour daily on days -3, -2.

Myeloablative Chemotherapy Regimen for Lymphoid Malignancies or Cord Blood Unit Recipients

Busulfan administration:

* For children \>/= 4 years of age, Busulfan 0.8 mg/kg/dose will be given every 6 hours over days -8,-7, -6, and -5 for a total of 16 doses.
* For children \< 4 years of age, Busulfan 1 mg/kg/dose will be given every 6 hours over days -8, -7, -6, -5 for a total of 16 doses.
* Pharmacokinetic analysis will guide dose modifications targeted to receive an average AUC of 800-1200 microMols\*min for the 16 doses.

Lorazepam (0.05 mg/kg) IV will be administered one half hour before the initial dose of Busulfan is given and every 6 hours through day -4.

Etoposide 1000 mg/m2 as a 24 hour continuous infusion started on day -4.

Cyclophosphamide 60 mg/kg/day IV given over 1 hour daily on days -3 and -2.

Myeloablative Chemotherapy Regimen for Non-Cord Blood Unit Recipients with Myeloid Malignancies

Hematopoietic progenitor cells (HPCs) will be infused on day 0. Source of cells may be bone marrow, peripheral blood cells, or cord blood units, from matched related or unrelated donors.

Hematopoietic Progenitor Cell Transplantation (HPCT)

Patients with prior CNS disease over the age of 1 year will be treated with 600 cGy of cranial irradiation in addition to 1200 cGy of TBI.

Patients diagnosed with ALL with CNS disease (at the time of diagnosis or relapse) \< 1 year of age will receive CNS treatment as Intrathecal Methotrexate as follows:

* Infants ≤ 1 year of age at the time of Intrathecal Therapy will receive a dosing of 7.5 mg once a month for 6 months after transplant beginning at day +30 with an adequate white count
* Children 1-2 years of age at the time of Intrathecal Therapy will receive 8 mg once a month for 6 months after transplant beginning at day +30 with an adequate white count

CNS radiation treatment for ALL with prior CNS disease patients

Morris Kletzel, MD

Terriss Conterato

The purpose of this study is to show that myeloablative hematopoietic progenitor cell transplantation (HPCT) continues to offer acceptable disease-free survival for select patients requiring HPCT.

Myeloablative hematopoietic progenitor cell transplantation (HPCT) remains the standard of care for patients requiring HPCT. The purpose of this study is to evaluate the morbidity and mortality of myeloablative HPCT at Children's Memorial Hospital. It will also look to determine the toxicity of a single conditioning regimen consisting of total body irradiation (TBI), etoposide (VP-16), and Cyclophosphamide for patients with transplant eligible lymphoid malignant conditions or with transplant eligible myeloid malignant conditions who are receiving cord blood units, or to determine the toxicity of a single conditioning regimen consisting of Busulfan and Cyclophosphamide for patients with transplant eligible myeloid malignant conditions who are not receiving cord blood units.

Myeloablative Hematopoietic Progenitor Cell Transplantation (HPCT) for Pediatric Malignancies

Ann & Robert H Lurie Children's Hospital of Chicago

Neoplasm Metastasis

Analgesics

Interleukin-2

Mesna

Denileukin diftitox

Antineoplastic Agents, Alkylating

Alkylating Agents

Analgesics, Non-Narcotic

Patients are treated with donor natural killer cells, fludarabine, cyclophosphamide, Denileukin diftitox, Donor lymphapheresis and IL-2.

Given by infusion on Day 0. The product is T cell-depleted (CD3-) and B cell-depleted (CD19). Target dose for infusion is \< or = 8 x 10\^7 nucleated cells/kilogram.

Natural Killer Cells

Administered as a 1 hour intravenous infusion once a day for 5 doses beginning on day -6.

Administered as a 2 hour intravenous infusion with high volume fluid flush and mesna per institutional guidelines on day -5 and -4 one hour after fludarabine infusion. (Day -4 administration may be omitted if patient has had a transplant in the previous 4 months.)

12 ug/kg/day will be administered on day -1 and day -2 intravenously.

Day -1 before planned NK cell infusion, the donor will undergo lymphapheresis (Removal of lymphocytes from donated blood, with the remainder of the blood retransfused into the donor).

Donor lymphapheresis

Administered after NK cell infusion, 10 million units every other day for a total of 6 doses. (Patients weighing less than 45 kilograms will receive a dose of 5 million units/m\^2 every other day for 6 doses).

IL-2

Jeffrey S. Miller, M.D.

This is a phase II therapeutic study of related donor HLA-haploidentical NK-cell based therapy after a high dose of fludarabine/cyclophosphamide with denileukin diftitox preparative regimen for the treatment of poor prognosis acute myelogenous leukemia (AML).

Patients achieving a complete remission and neutrophil recovery (ANC \> 500) for at least 4 weeks will be considered for allogeneic transplant to prolong remission (independent of this study).

All patients, including those who go on to transplant, will be followed to determine disease free survival, treatment related mortality, and time to relapse.

Haploidentical Natural Killer Cells to Treat Refractory or Relapsed Acute Myelogenous Leukemia (AML)

Adoptive Transfer of Haploidentical Natural Killer Cells to Treat Refractory or Relapsed AML MT2010-02

The primary objective of this study was to estimate the incidence of in vivo expansion of natural killer (NK) cells 14 days after infusion of an allogeneic donor product enriched for NK progenitors. Successful in vivo donor NK cell expansion was defined by measuring an absolute circulating donor-derived NK cell count of \>100 cells/ul in the patient's peripheral blood 14 days after infusion.

Disease response was defined as complete remission (disease response) by morphologic criteria including \<5% blasts in a moderately cellular or cellular marrow. Complete remission was also correlated with NK cell expansion in vivo, IL-15 levels and donor/recipient KIR B genotyping, and Treg depletion.

Number of patients alive and disease free at 6 months. The length of time after treatment ends that a patient survives without any signs or symptoms of that cancer or any other type of cancer. In a clinical trial, measuring the disease-free survival is one way to see how well a new treatment works.

Number of patients who have had a relapse(the return of disease after its apparent recovery/cessation) after obtaining a complete remission of their disease.

Number of patients who died within the first 100 days of treatment due to toxicity.

Association between in vivo natural killer (NK) cell expansion and complete response without platelet recovery (CRp) with donor killer immunoglobulin-like (KIR) genotype and Treg depletion. In vivo donor NK cell expansion was correlated with regulatory T-cell (Treg) depletion as detected on flow cytometry.

Masonic Cancer Center, University of Minnesota

Due to chemotherapy as prep for the NK cell infusion, it is expected that all patients will experience severe depression of their blood counts and other related toxicities. Adverse event (AE) collection will focus on targeted AEs and unexpected AEs at specific time points in relation to the NK cell infusion and IL-2 injections.

Patients with acute myeloid leukemia (AML) are treated with donor natural killer cells, fludarabine, cyclophosphamide, Denileukin diftitox, Donor lymphapheresis and IL-2.

Treated Patients

Evaluable (Treated) Patients

Age, Continuous

United States

Region of Enrollment

Patients with acute myeloid leukemia (AML) were treated with donor natural killer cells, fludarabine, cyclophosphamide, Denileukin diftitox, Donor lymphapheresis and IL-2.

Percent of Patients With Successful Expansion of Natural Killer Cells After Infusion

Percent of Patients With Complete Remission of Disease

Percent of Patients With Disease Free Survival

Percent of Patients With Incidence of Relapse

Number of Patients With Treatment-Related Death

KIR matched: Patients with acute myeloid leukemia (AML) were treated with donor natural killer cells, fludarabine, cyclophosphamide, Denileukin diftitox, Donor lymphapheresis and IL-2.

Evaluable (Treated) Patients (Expansion=No)

KIR mismatched: Patients with acute myeloid leukemia (AML) were treated with donor natural killer cells, fludarabine, cyclophosphamide, Denileukin diftitox, Donor lymphapheresis and IL-2.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
LCI-HEM-SPEC-001: Tissue Collection for Genetic Analysis of Acute Myelogenous Leukemia	NCT01999556	Leukemia, Myelo...		18 Years -	Wake Forest University Health Sciences
Clofarabine With Cytarabine for Patients With Minimal Residual Disease Positive Leukemia	NCT01158885	Minimal Residua... Leukemia, Lymph... Leukemia, Myelo...	Clofarabine Cytarabine intr... Methotrexate Intrathecal (IT...	1 Year - 21 Years	Therapeutic Advances in Childhood Leukemia Consortium
A Phase I Clinical Trial of OXi4503 for Relapsed and Refractory AML and MDS	NCT01085656	Leukemia, Myelo... Myelodysplastic...	OXi4503	18 Years -	University of Florida
Myeloablative Hematopoietic Progenitor Cell Transplantation (HPCT) for Pediatric Malignancies	NCT00619879	Leukemia, Myelo... Leukemia, Lymph... Leukemia, Myelo... Myeloproliferat... Lymphoma, Malig...	Myeloablative C... Myeloablative C... Hematopoietic P... CNS radiation t...	- 21 Years	Ann & Robert H Lurie Children's Hospital of Chicago
Haploidentical Natural Killer Cells to Treat Refractory or Relapsed Acute Myelogenous Leukemia (AML)	NCT01106950	Leukemia, Myelo...	Natural Killer ... Fludarabine Cyclophosphamid... Denileukin dift... Donor lymphaphe... IL-2	2 Years -	Masonic Cancer Center, University of Minnesota

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