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

Primary Purpose

Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia in Remission, Allogeneic Hematopoietic Stem Cell Transplantation Recipient

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Allogeneic Bone Marrow Transplantation
Allogeneic Hematopoietic Stem Cell Transplantation
Anti-Thymocyte Globulin
Busulfan
Clofarabine
Fludarabine Phosphate
Peripheral Blood Stem Cell Transplantation
Pharmacological Study
Vorinostat
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Lymphoblastic Leukemia in Remission

Eligibility Criteria

undefined - 60 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (vorinostat, chemotherapy, SCT)

Arm Description

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.

Outcomes

Primary Outcome Measures

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
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.

Secondary Outcome Measures

Recurrence-free survival
Will be estimated by the Kaplan and Meier method.
Overall survival
Will be estimated by the Kaplan and Meier method.

Full Information

First Posted
March 7, 2014
Last Updated
December 15, 2021
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT02083250
Brief Title
Fludarabine Phosphate, Clofarabine, and Busulfan With Vorinostat in Treating Patients With Acute Leukemia in Remission or Relapse Undergoing Donor Stem Cell Transplant
Official Title
Fludarabine/Clofarabine/Busulfan Combined With SAHA in Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation for Acute Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
December 2021
Overall Recruitment Status
Completed
Study Start Date
March 6, 2014 (Actual)
Primary Completion Date
November 12, 2021 (Actual)
Study Completion Date
November 12, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
70 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (vorinostat, chemotherapy, SCT)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Allogeneic Bone Marrow Transplantation
Other Intervention Name(s)
Allo BMT, Allogeneic BMT
Intervention Description
Undergo allogeneic peripheral blood stem cell or bone marrow transplant
Intervention Type
Procedure
Intervention Name(s)
Allogeneic Hematopoietic Stem Cell Transplantation
Other Intervention Name(s)
Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT
Intervention Description
Undergo allogeneic peripheral blood stem cell or bone marrow transplant
Intervention Type
Biological
Intervention Name(s)
Anti-Thymocyte Globulin
Other Intervention Name(s)
Antithymocyte Globulin, Antithymocyte Serum, ATG, ATGAM, ATS, Thymoglobulin
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Busulfan
Other Intervention Name(s)
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
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Clofarabine
Other Intervention Name(s)
Clofarex, Clolar
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Fludarabine Phosphate
Other Intervention Name(s)
2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
Peripheral Blood Stem Cell Transplantation
Other Intervention Name(s)
PBPC transplantation, PBSCT, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplant, Peripheral Stem Cell Transplantation
Intervention Description
Undergo allogeneic peripheral blood stem cell or bone marrow transplant
Intervention Type
Other
Intervention Name(s)
Pharmacological Study
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
Vorinostat
Other Intervention Name(s)
L-001079038, MSK-390, SAHA, Suberanilohydroxamic Acid, Suberoylanilide Hydroxamic Acid, Zolinza
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
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
Description
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.
Time Frame
30 days
Secondary Outcome Measure Information:
Title
Recurrence-free survival
Description
Will be estimated by the Kaplan and Meier method.
Time Frame
Up to 5 years
Title
Overall survival
Description
Will be estimated by the Kaplan and Meier method.
Time Frame
Up to 5 years

10. Eligibility

Sex
All
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Partow Kebriaei
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mdanderson.org
Description
MD Anderson Cancer Center Website

Learn more about this trial

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

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