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Acute Lymphoblastic Leukemia in RemissionPhase 1NCT02083250

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

A Phase 1 study testing Allogeneic Bone Marrow Transplantation, Allogeneic Hematopoietic Stem Cell Transplantation and Anti-Thymocyte Globulin in people with Acute Lymphoblastic Leukemia in Remission and Acute Myeloid Leukemia in Remission, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages Up to 60 years
What is being tested?
Allogeneic Bone Marrow Transplantation, Allogeneic Hematopoietic Stem Cell Transplantation and Anti-Thymocyte Globulin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
70 participants
Where
1 siteUnited States
Study dates
6 Mar 2014to 12 Nov 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 60 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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
Show all 11Show fewer
  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site
  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: 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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
Allogeneic Bone Marrow Transplantation, Allogeneic Hematopoietic Stem Cell Transplantation, Anti-Thymocyte Globulin, Busulfan, Clofarabine
Medical subject headings
Myelodysplastic Syndromes, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Allogeneic Bone Marrow TransplantationProcedure or surgery

    Also called Allo BMT, Allogeneic BMT

    Undergo allogeneic peripheral blood stem cell or bone marrow transplant

  • Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery

    Also called Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT

    Undergo allogeneic peripheral blood stem cell or bone marrow transplant

  • Anti-Thymocyte GlobulinBiological

    Also called Antithymocyte Globulin, Antithymocyte Serum, ATG, ATGAM

    Given IV

  • BusulfanDrug

    Also called 1, 4-Bis[methanesulfonoxy]butane, BUS, Bussulfam, Busulfanum

    Given IV

  • ClofarabineDrug

    Also called Clofarex, Clolar

    Given IV

  • Fludarabine PhosphateDrug

    Also called 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara

    Given IV

  • Peripheral Blood Stem Cell TransplantationProcedure or surgery

    Also called PBPC transplantation, PBSCT, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support

    Undergo allogeneic peripheral blood stem cell or bone marrow transplant

  • Pharmacological StudyOther

    Correlative studies

  • VorinostatDrug

    Also called L-001079038, MSK-390, SAHA, Suberanilohydroxamic Acid

    Given PO

Study groups in NCT02083250
Study groupRoleWhat they receive
Treatment (vorinostat, chemotherapy, SCT)ExperimentalCONDITIONING 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.
Receives: Procedure: Allogeneic Bone Marrow Transplantation; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Biological: Anti-Thymocyte Globulin; Drug: Busulfan; Drug: Clofarabine; Drug: Fludarabine Phosphate; Procedure: Peripheral Blood Stem Cell Transplantation; Other: Pharmacological Study; Drug: Vorinostat

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 30 days

Secondary outcomes (2)
  1. Recurrence-free survival

    Will be estimated by the Kaplan and Meier method.

    Measured: Up to 5 years

  2. Overall survival

    Will be estimated by the Kaplan and Meier method.

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Mar 2014 (estimated)
  2. Study start6 Mar 2014
  3. Primary completion12 Nov 2021
  4. Study completion12 Nov 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
70 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02083250
Sponsor's protocol ID
2012-0999
Other IDs
NCI-2014-01982, 2012-0999, P30CA016672
Status last verified
Dec 2021
First submitted
7 Mar 2014
Last updated
6 Jan 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Allogeneic Bone Marrow Transplantation, Allogeneic Hematopoietic Stem Cell Transplantation and Anti-Thymocyte Globulin in people with Acute Lymphoblastic Leukemia in Remission and Acute Myeloid Leukemia in Remission, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2022.

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