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

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Cytarabine

Daunorubicin

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Within 14-33 days after the start of previous cycle of chemotherapy, patients receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3 in the absence of disease progression or unacceptable toxicity.

Liposome-encapsulated Daunorubicin-Cytarabine

The Ohio State University Comprehensive Cancer Center

Brian Jonas, MD, PhD

Gregory K. Behbehani, MD, PhD

Ana Swatzell

Gregory K Behbehani, MD, PhD

This phase II trial studies the side effects and how well Vyxeos works in treating patients with intermediate and high-risk acute myeloid leukemia who have failed an initial cycle of standard cytarabine and daunorubicin chemotherapy. Vyxeos is a combination of both chemotherapy drugs cytarabine and daunorubicin contained in a liposome. Drugs used in chemotherapy, such as cytarabine and daunorubicin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Cytarabine and daunorubicin given together in liposomes may have fewer side effects and work better than cytarabine and daunorubicin given alone in patients with acute myeloid leukemia.

PRIMARY OBJECTIVES:

I. To demonstrate the safety and estimate the efficacy of liposome-encapsulated daunorubicin-cytarabine (Vyxeos) in acute myeloid leukemia (AML) patients who have failed to achieve a hypocellular marrow after an initial course of 7+3.

SECONDARY AND/OR EXPLORATORY OBJECTIVES:

I. Determination of rate of morphologic leukemia-free state (MLFS). II. Determination of progression-free survival (PFS), and overall survival (OS) at 2 years.

III. Mass cytometric measurement relative clearance of quiescent leukemia stem/repopulating cells (LSCs) and blasts as compared to the same patient's preceding cycle of 7+3 and to a separate control population receiving re-induction with traditional 7+3.

IIIa. Measurement of blast cell cycle fraction before and after Vyxeos treatment.

IIIb. Relative clearance immunophenotypically abnormal blast and stem cells after Vyxeos.

IIIc. Comparison of efficacy of blast cell and LSC elimination in patients receiving Vyxeos re-induction compared to similar blast cells and LSCs in patients receiving standard 7+3 or 5+2 re-induction.

OUTLINE:

Within 14-33 days after the start of previous cycle of chemotherapy, patients receive liposome-encapsulated daunorubicin-cytarabine intravenously (IV) over 90 minutes on days 1 and 3 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up weekly for 60 days, then at least monthly for 2 years.

Vyxeos for Re-induction Treatment of Acute Myeloid Leukemia Patients With Persistent Disease After Induction

Open-Label Phase 2 Trial of Vyxeos in Patients With Intermediate and High-Risk Acute Myeloid Leukemia Who Have Failed an Initial Cycle of Standard Cytarabine and Daunorubicin Chemotherapy

Will be exploratory in nature with graphical methods and descriptive statistics provided to gather preliminary information. Nonparametric method such Mann-Whitney U test will be utilized to compare pre and post-treatment data, and box plot or spaghetti plot will be presented to help visualize the trend of change.

Will compare the efficacy of blast cell and LSC elimination in patients receiving Vyxeos re-induction compared to similar blast cells and LSCs in patients receiving standard 7+3 or 5+2 re-induction. Will be exploratory in nature with graphical methods and descriptive statistics provided to gather preliminary information. Nonparametric method such Mann-Whitney U test will be utilized to compare pre and post-treatment data, and box plot or spaghetti plot will be presented to help visualize the trend of change.

Will be measured and is exploratory in nature. It will be analyzed with descriptive statistics to gather preliminary information and compared to historical controls.

Will be measured by the time to count recovery, incidence of symptomatic cardiac dysfunction, incidence of hepatic or renal toxicity, incidence of severe hemorrhage, and incidence of severe infection. Will be summarized by National Cancer Institute Common Terminology Criteria for Adverse Events version 4, and frequency counts will be tabulated with a focus on severe (grade 3+) adverse events and toxicities that are deemed at least possibly related to study treatment. The incidence of specific toxicities will be calculated as the proportion of patients experience these toxicities over all patients who receive any study drug.

CR and CRi rate will be defined as the proportion of patients who achieve CR or CRi over all evaluable patients. The rates will be provided with 95% binomial confidence intervals.

Will be calculated by the method of Kaplan-Meier, with the 2-year estimate provided with 95% confidence interval.

Ohio State University Comprehensive Cancer Center

Principal Investigator

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Symptoms and General Pathology

Uterine Cervical Neoplasms

Recurrence

Carcinoma

Adenocarcinoma

Carcinoma, Squamous Cell

Carcinoma, Adenosquamous

Neoplasms, Glandular and Epithelial

Disease Attributes

Neoplasms, Squamous Cell

Patients receive brivanib alaninate PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Brivanib Alaninate

Laboratory Biomarker Analysis

John K Chan

This phase II trial studies how well brivanib alaninate works in treating patients with cervical cancer that has come back. Brivanib alaninate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor.

PRIMARY OBJECTIVES:

I. To estimate the proportion of patients with persistent or recurrent cervical cancer, who survive progression-free for at least 6 months and the proportion of patients who have objective tumor response (complete or partial), treated with brivanib (brivanib alaninate).

II. To determine the nature and degree of toxicity of brivanib in this cohort of patients.

SECONDARY OBJECTIVES:

I. To estimate the progression-free survival (PFS) and overall survival (OS) of patients with persistent or recurrent cervical cancer treated with brivanib.

TERTIARY OBJECTIVES:

I. To obtain the serum expression levels of surrogate markers of brivanib effects including angiogenic factors (vascular endothelial growth factor \[VEGF\] and basic fibroblast growth factor \[bFGF\]) and markers of endothelial damage (E-selectin, vascular cell adhesion molecule 1 \[VCAM-1\], and (intercellular adhesion molecule 1 \[ICAM-1\]). (exploratory) II. To determine whether these marker expression levels alone or in combination are associated with response, PFS, or overall survival. (exploratory)

OUTLINE:

Patients receive brivanib alaninate orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Brivanib Alaninate in Treating Patients With Persistent or Recurrent Cervical Cancer

A Phase II Evaluation of Brivanib (BMS582664) in the Treatment of Persistent or Recurrent Carcinoma of the Cervix (BMS Study CA182-048)

Surrogate markers will be associated with response, PFS, and OS.

Proportion of participants with objective tumor response. Objective tumor response is defined as complete or partial tumor response assessed by RECIST 1.1

Proportion of participants who survive progression-free for at least 6 months without non-protocol therapy from study entry. Progression is assessed by RECIST 1.1.

Number of participants with a maximum grade of 3 or higher during treatment period. Adverse events are graded and categorized using CTCAE v.4.0

Progression-free survival is the period of time from study entry to time of disease progression, death or date of last contact, whichever occurs first. Progression is assessed by RECIST 1.1

Overall survival is defined as the duration of time from study entry to time of death or the date of last contact..

National Cancer Institute (NCI)

Gynecologic Oncology Group

Brivanib 800mg administered orally every day on days 1 to 28 of each cycle until disease progression or adverse effects prohibit further treatment. One cycle is 28 days.

Brivanib

30-39 years

40-49 years

50-59 years

60-69 years

70-79 years

Age, Customized

Sex/Gender, Customized

Linda Gedeon for Wei Deng,PhD

Objective Tumor Response

PFS for at Least 6 Months Without Non-protocol Therapy From Study Entry.

Leukopenia

Thrombocytopenia

Neutropenia

Anemia

Other Investigations

Cardiac Disorders

Gastrointestinal Disorders

General disorders & administration site conditions

Hepatobiliary Disorders

Infections and infestations

Metabolism and nutrition disorders

Musculoskeletal & connective tissue disorders

Neoplasms benign, malignant & unspecified

Nervous system disorders

Renal and urinary disorders

Vascular Disorders

Adverse Events (Grade 3 or Higher) During Treatment Period

Progression-free Survival

Overall Survival

Serum Expression Levels of Surrogate Markers of Brivanib Alaninate Effects Including Angiogenic Factors (VEGF and bFGF) and Markers of Endothelial Damage (E-selectin, VCAM-1, and ICAM-1)

Overall Study

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Chronic Graft Versus Host Disease

Chronic Myeloid Leukemia

Chronic Myeloproliferative Disorders

Fludarabine

Fludarabine phosphate

Immunomodulating Agents

Busulfan

Alkylating Agents

Antineoplastic Agents, Alkylating

Unrelated Donor Transplant/ Cord Blood Transplant

Reduced Intensity Conditioning, Busulfan and Fludarabine

Mtchell S Cairo, MD

CML, a malignant disorder of stem cells, is characterized by increases in both immature and mature myeloid, erythroid, and lymphoid cells, as well as platelets in the peripheral blood. The cytogenetic hallmark of CML is the Philadelphia(Ph)chromosome found in the malignant cells of 95% of patients. CML comprises 7-20% of all leukemias with an overall incidence in the general population estimated at 1 to 2 per 100,000. The peak incidence occurs in the fifth decade, however, all age groups, including children, are affected. The only reported environmental risk factor is exposure to excessive ionizing radiation that is documented in only a very small percentage of patients. Clinically, CML is characterized by an initial chronic phase in which patients may report mild constitutional symptoms; however, 40-50% are asymptomatic and are diagnosed based upon abnormal blood counts discovered during a routine examination. The chronic phase typically lasts three to five years, and is followed by an accelerated phase distinguished by progressive systemic symptoms, an increasing resistance to conventional chemotherapy, and a rise in the peripheral blood and bone marrow blast count. This evolves rapidly into a blastic crisis characterized by immature cells resembling the blasts characteristic of acute leukemia. The presence of 30% or more blastic cells in the blood or marrow is diagnostic of this final blastic phase which is typically fatal within 3 to 6 months.

The primary treatment options for CML have traditionally been monotherapy with either busulfan or hydroxyurea. Both agents are able to control the clinical symptoms associated with CML, as well as induce hematological remissions in 80% of chronic phase patients. However, complete cytogenetic remissions with either agent are rare, and neither is able to prevent eventual progression to the terminal blastic phase; therefore, these therapies can only be considered palliative.

The primary purpose of this clinical research trial is to study the feasibility of a reduced intensity allogenic transplant for CML. This study will also determine the side effects as well as the response rate.

Further study details will be provided by Columbia University, Division of Pediatric Blood and Marrow Transplantation.

STUDY DESIGN:

Patients less than 30 years of age with CML in 1st or 2nd chronic phase or 1st accelerated phase and a matched related donor, an unrelated cord blood donor, or an unrelated adult donor, will receive 6 days of IV Fludarabine, 4 doses of IV Busulfex, and 5 doses of Alemtuzumab. Patients with persistant RT-PCR positive BCR-Abl and/or Philadelphia chromosome positivity by cytogentics after Day + 100 and a matched related donor would receive DLIx1. If still BCR-Abl or Philadelphia chromosome positive at Day +180 and a matched related donor, patients would receive a second dose of DLI. All patients will receive STI-571 (Gleevec) after hematological reconstitution. Studies for immune reconstitution, chimersim, and MRD will be performed postt AlloSCT.

Reduced Intensity AlloSCT in(CML) With Persistent Disease

A Pilot Study of Reduced Intensity Allogeneic Stem Cell Transplantation in Patients With Chronic Myeloid Leukemia (CML) and Adoptive Cellular Immunotherapy Only in Patients With Persistent Disease and Matched Family Donors

Columbia University

Mitchell Cairo, MD

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Vyxeos for Re-induction Treatment of Acute Myeloid Leukemia Patients With Persistent Disease After Induction	NCT04049539	Blasts More Tha... Persistent Dise... Refractory Acut...	Liposome-encaps...	18 Years - 75 Years	Ohio State University Comprehensive Cancer Center
Brivanib Alaninate in Treating Patients With Persistent or Recurrent Cervical Cancer	NCT01267253	Cervical Adenoc... Cervical Adenos... Cervical Squamo... Persistent Dise... Recurrent Cervi...	Brivanib Alanin... Laboratory Biom...	18 Years -	GOG Foundation
Reduced Intensity AlloSCT in(CML) With Persistent Disease	NCT00531310	Chronic Myeloid...	Reduced Intensi...	- 30 Years	Columbia University

Spots Global Cancer Trial Database for persistent disease