Fludarabine/Clofarabine/Busulfan Combined With SAHA in Acute Leukemia
Information source: M.D. Anderson Cancer Center
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Leukemia
Intervention: Fludarabine (Drug); Clofarabine (Drug); Busulfan (Drug); SAHA (Drug); Stem Cell Infusion (SCT) (Procedure); Thymoglobulin (Drug)
Phase: Phase 1
Status: Recruiting
Sponsored by: M.D. Anderson Cancer Center Official(s) and/or principal investigator(s): Partow Kebriaei, MD, Principal Investigator, Affiliation: M.D. Anderson Cancer Center
Overall contact: Partow Kebriaei, MD, Phone: 713-745-0663
Summary
The goal of this clinical research study is to evaluate the safety of combining vorinostat
(also called SAHA) with fludarabine, clofarabine, and busulfan.
Clinical Details
Official title: Fludarabine/Clofarabine/Busulfan Combined With SAHA in Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation for Acute Leukemia
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Maximum Tolerated dose (MTD) of SAHA in Combination with Fludarabine, Clofarabine, and Busulfan
Detailed description:
Study Groups:
All participants will receive the same dose levels of fludarabine, clofarabine, and
busulfan. You will be assigned to a dose level of vorinostat based on when you joined this
study. Up to 6 dose levels of vorinostat may be tested. Up to 3 participants may be
enrolled at each dose level.
The first group of participants will receive the first dose level of vorinostat. Each new
group will receive a higher dose than the group before it, if no intolerable side effects
are seen. When the highest tolerated dose level is found, more participants may be enrolled
at that level.
For a stem cell transplant, the days before you receive your stem cells are called minus
days. The day you receive the stem cells is called Day 0. The days after you receive the
stem cells are called plus days.
Study Drug Administration and Procedures:
All groups will receive a "test" dose of busulfan by vein over about 45 minutes to 1 hour.
This low-level test dose of busulfan is to check how fast busulfan is processed by your body
and cleared from your blood. This information will determine the amount of busulfan you
will receive. You may receive the busulfan test dose as an outpatient during the week
before you are admitted to the hospital or as an inpatient 8 days before your stem cell
transplant.
About 11 samples of blood (about 1 teaspoon each time) will be drawn for pharmacokinetic
(PK) testing. PK testing measures the amount of study drug in the body at different time
points and will also help determine your dose of busulfan. These blood samples will be
drawn at various times before you receive the test dose of busulfan and over the next 11
hours. These blood draws will be repeated again on the first day of high-dose busulfan
treatment (Day - 6, which is 6 days before the transplant).
A heparin lock line will be placed in your vein to lower the number of needle sticks needed
for these draws. If it is not possible for the PK tests to be performed for technical or
scheduling reasons, you will receive the standard fixed dose of busulfan.
On Days - 6 through -3, you will receive vorinostat as a tablet by mouth once a day, then
fludarabine by vein over 1 hour, then clofarabine by vein over 1 hour, and then busulfan by
vein over 3 hours.
If you are going to be receiving a transplant from an HLA-matched unrelated donor, you will
also receive antithymocyte globulin (ATG) by vein over 4 hours on the 3 days before the
transplant. This drug is designed to further weaken your immune system to reduce the risk
of rejecting the transplant.
You will be given standard drugs to help decrease the risk of side effects. You may ask the
study staff for information about how the drugs are given and their risks.
While you are in the hospital, you will be checked for any side effects as part of your
standard of care. Blood (about 2 teaspoons) will be drawn every day to check for side
effects, for routine tests, to check your blood counts, kidney and liver function, and to
check for infections. Tests may be repeated, if your doctor thinks it is needed.
As part of standard care, you will remain in the hospital for about 3-4 weeks after the
transplant. After you are released from the hospital, you must remain in the Houston area
to be monitored for infections and other transplant side effects until about 3 months after
transplant. During this time, you will return to the clinic at least 1 time each week. The
following tests and procedures will be performed:
- Blood (about 2 teaspoons) will be drawn for routine tests.
Around 14-30 days after the transplant (when the transplant "engrafts", or "takes"), you
will have a bone marrow aspirate to check the status of the disease. To collect a bone
marrow aspirate, an area of the hip or other site is numbed with anesthetic, and a small
amount of bone marrow is withdrawn through a large needle.
Around Day 30, if you have ALL, you will have a lumbar puncture to check the status of the
disease. To perform a lumbar puncture (also called a spinal tap), a special needle is
inserted into the lower back through the space between the bones. The needle is used to
draw a sample of the fluid that surrounds the spinal cord.
Around Day 30, and about 3, 6, and 12 months after the transplant, the following tests and
procedures will be performed:
- You will have a physical exam.
- Blood (about 2 teaspoons) will be drawn to see how well the transplant has taken.
- You will have a bone marrow aspiration to check the status of the disease.
After the first year from transplant through the end of your participation in the study, the
study staff may also call you and your local doctor to ask about your health. This call may
take about 10 minutes.
Length of Study:
You will be taken off study 5 years after the end of treatment. You may be taken off study
early if the disease gets worse, if you have any intolerable side effects, if the stem cell
transplant does not "take", if the disease relapses (returns), or if you are unable to
follow study directions.
You should talk to the study doctor if you want to leave the study early. If you are taken
off study early, you still may need to return for routine post-transplant follow-up visits,
if your transplant doctor decides it is needed.
It may be life-threatening to leave the study after you have begun to receive the study
drugs but before you receive the stem cells.
This is an investigational study. Fludarabine, clofarabine, and vorinostat are FDA approved
and commercially available for the treatment of cancer. Busulfan is also FDA approved for
use with stem cell transplants. The use of these drugs together with a stem cell transplant
is investigational. The study doctor can explain how the study drugs are designed to work.
Up to 72 patients will take part in this study. All will be enrolled at MD Anderson.
Eligibility
Minimum age: N/A.
Maximum age: 60 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. Patients with biopsy-proven acute lymphoblastic leukemia, acute myeloid leukemia, or
myelodysplastic syndrome in remission or relapse.
2. Estimated creatinine clearance at least 50 ml/min.
3. Bilirubin equal or less than 1. 5 (unless Gilbert's Syndrome), SGPT <3 X upper limit
of normal and alkaline phosphatase <2 X upper limit of normal.
4. Pulmonary function with FEV1, FVC and 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.
5. Adequate cardiac function with left ventricular ejection fraction at least 45% on
appropriate medical therapy. No uncontrolled arrhythmias or symptomatic cardiac
disease.
6. Zubrod performance status 0-1 or Lansky/Karnofsky PS equal or greater to 80%.
7. Patients must have a related, genotypically HLA identical donor, or they must have a
unrelated donor who is 8/8 HLA match by high resolution typing.
8. 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.
9. Negative Beta HCG test in a woman with child bearing potential defined as not
post-menopausal for 12 months and no previous surgical sterilization.
Exclusion Criteria:
1. Patients with active CNS disease.
2. Evidence of acute or chronic active hepatitis or cirrhosis.
3. Uncontrolled infection, including HIV, HTLV-1, hepatitis B or hepatitis C viremia.
4. Patients greater than 60 years-old.
5. Prior allogeneic SCT.
6. Prior autologous SCT in last 12 months.
7. Patients with 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 (NPM1).
8. Patients with ALL in first complete remission after one course of induction without
minimal residual disease.
9. Prior radiation to liver in form of total body or involved field.
Locations and Contacts
Partow Kebriaei, MD, Phone: 713-745-0663
University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States; Recruiting
Additional Information
University of Texas MD Anderson Cancer Center Website
Starting date: March 2014
Last updated: August 7, 2015
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