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

December 15, 2021 updated by: M.D. Anderson Cancer Center

Fludarabine/Clofarabine/Busulfan Combined With SAHA in Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation for Acute Leukemia

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

70

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • M D Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 56 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Other: Pharmacological Study
Correlative studies
Drug: Clofarabine
Given IV
Other Names:
  • Clofarex
  • Clolar
Biological: Anti-Thymocyte Globulin
Given IV
Other Names:
  • ATGAM
  • ATG
  • Antithymocyte Globulin
  • Antithymocyte Serum
  • ATS
  • Thymoglobulin
Drug: Fludarabine Phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
  • 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
  • SH T 586
Drug: Busulfan
Given IV
Other Names:
  • Busulfex
  • Misulfan
  • Mitosan
  • Myeloleukon
  • Myelosan
  • 1, 4-Bis[methanesulfonoxy]butane
  • BUS
  • Bussulfam
  • Busulfanum
  • Busulphan
  • CB 2041
  • CB-2041
  • Glyzophrol
  • GT 41
  • GT-41
  • Joacamine
  • Methanesulfonic Acid Tetramethylene Ester
  • Methanesulfonic acid, tetramethylene ester
  • Mielucin
  • Misulban
  • Myeleukon
  • Mylecytan
  • Myleran
  • Sulfabutin
  • Tetramethylene Bis(methanesulfonate)
  • Tetramethylene bis[methanesulfonate]
  • WR-19508
Drug: Vorinostat
Given PO
Other Names:
  • SAHA
  • Suberoylanilide Hydroxamic Acid
  • MSK-390
  • Zolinza
  • L-001079038
  • Suberanilohydroxamic Acid
Procedure: Allogeneic Bone Marrow Transplantation
Undergo allogeneic peripheral blood stem cell or bone marrow transplant
Other Names:
  • Allo BMT
  • Allogeneic BMT
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic peripheral blood stem cell or bone marrow transplant
Other Names:
  • Allogeneic Hematopoietic Cell Transplantation
  • Allogeneic Stem Cell Transplantation
  • HSC
  • HSCT
Procedure: Peripheral Blood Stem Cell Transplantation
Undergo allogeneic peripheral blood stem cell or bone marrow transplant
Other Names:
  • PBPC transplantation
  • Peripheral Blood Progenitor Cell Transplantation
  • Peripheral Stem Cell Support
  • Peripheral Stem Cell Transplantation
  • PBSCT
  • Peripheral Stem Cell Transplant

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum tolerated dose of vorinostat when given in combination with fludarabine phosphate, clofarabine, and busulfan before stem cell transplant assessed using Common Terminology Criteria for Adverse Events version 4
Time Frame: 30 days
The 2-stage time-to-event continual reassessment method will be used. Toxicity will be tabulated by dose, type, and grade. The probability of toxicity over 30 days as a function of dose will be estimated by fitting a Bayesian binary outcome regression model.
30 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recurrence-free survival
Time Frame: Up to 5 years
Will be estimated by the Kaplan and Meier method.
Up to 5 years
Overall survival
Time Frame: Up to 5 years
Will be estimated by the Kaplan and Meier method.
Up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

M.D. Anderson Cancer Center

Collaborators

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 6, 2014

Primary Completion (Actual)

November 12, 2021

Study Completion (Actual)

November 12, 2021

Study Registration Dates

First Submitted

March 7, 2014

First Submitted That Met QC Criteria

March 7, 2014

First Posted (Estimate)

March 11, 2014

Study Record Updates

Last Update Posted (Actual)

January 6, 2022

Last Update Submitted That Met QC Criteria

December 15, 2021

Last Verified

December 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2012-0999 (Other Identifier: M D Anderson Cancer Center)
  • P30CA016672 (U.S. NIH Grant/Contract)
  • NCI-2014-01982 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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