Fludarabine Phosphate, Clofarabine, and Busulfan With Vorinostat in Treating Patients With Acute Leukemia in Remission or Relapse Undergoing Donor Stem Cell Transplant

NCT ID: NCT02083250

Last Updated: 2022-01-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

70 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-03-06

Study Completion Date

2021-11-12

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This phase I trial studies the side effects and best dose of vorinostat when given together with fludarabine phosphate, clofarabine, and busulfan in treating patients with acute leukemia that is under control (remission) or has returned (relapse) undergoing donor stem cell transplant. Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fludarabine phosphate, clofarabine, and busulfan, 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. Giving vorinostat together with fludarabine phosphate, clofarabine, and busulfan before a donor stem cell transplant may be a better treatment for patients with acute leukemia.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of SAHA (vorinostat) in combination with the preparative regimen fludarabine (fludarabine phosphate), clofarabine, and busulfan followed by allogeneic hematopoietic stem cell transplantation (SCT) for patients with advanced acute leukemia.

SECONDARY OBJECTIVES:

I. To determine the rate of graft versus host disease (GVHD), engraftment, progression-free survival (PFS) and overall survival (OS) for this treatment regimen.

OUTLINE: This is a dose-escalation study of vorinostat.

CONDITIONING REGIMEN: Patients receive vorinostat orally (PO) once daily (QD), fludarabine phosphate intravenously (IV) over 1 hour, clofarabine IV over 1 hour, and busulfan IV over 3 hours on days -6 to -3. Patients receiving a transplant from a human leukocyte antigen (HLA)-matched unrelated donor, receive anti-thymocyte globulin IV over 4 hours on days -3 to -1.

TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell or bone marrow transplant on day 0.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Acute Lymphoblastic Leukemia in Remission Acute Myeloid Leukemia in Remission Allogeneic Hematopoietic Stem Cell Transplantation Recipient Myelodysplastic Syndrome Previously Treated Myelodysplastic Syndrome Recurrent Acute Lymphoblastic Leukemia Recurrent Acute Myeloid Leukemia

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Treatment (vorinostat, chemotherapy, SCT)

CONDITIONING REGIMEN: Patients receive vorinostat PO QD, fludarabine phosphate IV over 1 hour, clofarabine IV over 1 hour, and busulfan IV over 3 hours on days -6 to -3. Patients receiving a transplant from a HLA-matched unrelated donor, receive anti-thymocyte globulin IV over 4 hours on days -3 to -1.

TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell or bone marrow transplant on day 0.

Group Type EXPERIMENTAL

Allogeneic Bone Marrow Transplantation

Intervention Type PROCEDURE

Undergo allogeneic peripheral blood stem cell or bone marrow transplant

Allogeneic Hematopoietic Stem Cell Transplantation

Intervention Type PROCEDURE

Undergo allogeneic peripheral blood stem cell or bone marrow transplant

Anti-Thymocyte Globulin

Intervention Type BIOLOGICAL

Given IV

Busulfan

Intervention Type DRUG

Given IV

Clofarabine

Intervention Type DRUG

Given IV

Fludarabine Phosphate

Intervention Type DRUG

Given IV

Peripheral Blood Stem Cell Transplantation

Intervention Type PROCEDURE

Undergo allogeneic peripheral blood stem cell or bone marrow transplant

Pharmacological Study

Intervention Type OTHER

Correlative studies

Vorinostat

Intervention Type DRUG

Given PO

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Allogeneic Bone Marrow Transplantation

Undergo allogeneic peripheral blood stem cell or bone marrow transplant

Intervention Type PROCEDURE

Allogeneic Hematopoietic Stem Cell Transplantation

Undergo allogeneic peripheral blood stem cell or bone marrow transplant

Intervention Type PROCEDURE

Anti-Thymocyte Globulin

Given IV

Intervention Type BIOLOGICAL

Busulfan

Given IV

Intervention Type DRUG

Clofarabine

Given IV

Intervention Type DRUG

Fludarabine Phosphate

Given IV

Intervention Type DRUG

Peripheral Blood Stem Cell Transplantation

Undergo allogeneic peripheral blood stem cell or bone marrow transplant

Intervention Type PROCEDURE

Pharmacological Study

Correlative studies

Intervention Type OTHER

Vorinostat

Given PO

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Allo BMT Allogeneic BMT Allogeneic Hematopoietic Cell Transplantation Allogeneic Stem Cell Transplantation HSC HSCT Antithymocyte Globulin Antithymocyte Serum ATG ATGAM ATS Thymoglobulin 1, 4-Bis[methanesulfonoxy]butane BUS Bussulfam Busulfanum Busulfex Busulphan CB 2041 CB-2041 Glyzophrol GT 41 GT-41 Joacamine Methanesulfonic Acid Tetramethylene Ester Methanesulfonic acid, tetramethylene ester Mielucin Misulban Misulfan Mitosan Myeleukon Myeloleukon Myelosan Mylecytan Myleran Sulfabutin Tetramethylene Bis(methanesulfonate) Tetramethylene bis[methanesulfonate] WR-19508 Clofarex Clolar 2-F-ara-AMP 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)- Beneflur Fludara SH T 586 PBPC transplantation PBSCT Peripheral Blood Progenitor Cell Transplantation Peripheral Stem Cell Support Peripheral Stem Cell Transplant Peripheral Stem Cell Transplantation L-001079038 MSK-390 SAHA Suberanilohydroxamic Acid Suberoylanilide Hydroxamic Acid Zolinza

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Patients with biopsy-proven acute lymphoblastic leukemia, acute myeloid leukemia, or myelodysplastic syndrome in remission or relapse
* Estimated creatinine clearance at least 50 ml/min
* Bilirubin equal or less than 1.5 (unless Gilbert's syndrome)
* Serum glutamate pyruvate transaminase (SGPT) \< 3 x upper limit of normal
* Alkaline phosphatase \< 2 x upper limit of normal
* Pulmonary function with forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO) at least 45% of expected corrected for hemoglobin; children unable to perform pulmonary functions must have an oxygen saturation greater than 92% at room air
* Left ventricular ejection fraction at least 45% on appropriate medical therapy; no uncontrolled arrhythmias or symptomatic cardiac disease
* Zubrod performance status 0-1 or Lansky/Karnofsky performance status (PS) equal or greater to 80%
* Patients must have a related, genotypically HLA identical donor, or they must have an unrelated donor who is 8/8 HLA match by high resolution typing
* Patient or patient's legal representative, parent(s) or guardian should provide written informed consent; assent of a minor if participant's age is at least seven and less than eighteen years
* Negative beta human chorionic gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 12 months and no previous surgical sterilization

Exclusion Criteria

* Patients with active central nervous system (CNS) disease
* Evidence of acute or chronic active hepatitis or cirrhosis
* Uncontrolled infection, including human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV)-1, hepatitis B or hepatitis C viremia
* Prior allogeneic SCT
* Prior autologous SCT in last 12 months
* Patients with acute myeloid leukemia (AML) in first remission after one course of induction and with favorable cytogenetics (t\[8;21\], inv 16, or t\[15;17\]) and/or molecular profile (nucleophosmin \[NPM\]1)
* Prior radiation to liver in form of total body or involved field
Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Partow Kebriaei

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

M D Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

Related Links

Access external resources that provide additional context or updates about the study.

http://www.mdanderson.org

MD Anderson Cancer Center Website

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

NCI-2014-01982

Identifier Type: REGISTRY

Identifier Source: secondary_id

2012-0999

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA016672

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2012-0999

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.