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LeukemiaPhase 2NCT00990249

Busulfan Plus Clofarabine Followed by Allogeneic Hematopoietic Stem Cell Transplantation

A Phase 2 study testing Busulfan, Clofarabine and Thymoglobulin in people with Leukemia and Lymphoma, 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

The goal of this clinical research study is to test the safety of giving clofarabine in combination with busulfan, followed by an allogeneic (from a donor) stem cell transplant, in patients with advanced leukemia or lymphoma. Read more about this study

Who is it for?
Ages Up to 65 years
What is being tested?
Busulfan, Clofarabine and Thymoglobulin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
120 participants
Where
1 siteUnited States
Study dates
Oct 2009to May 2016
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 65 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Patients with biopsy-proven acute lymphoblastic leukemia, acute lymphoblastic lymphoma, or acute biphenotypic leukemia in remission or relapse.
  • Adequate renal function, as defined by estimated serum creatinine clearance >60 ml/min.
  • Bilirubin equal or less than 1.5 (unless Gilbert's Syndrome), serum glutamate pyruvate transaminase (SGPT) <3 X upper limit of normal and alkaline phosphatase <2 X upper limit of normal.
  • Adequate pulmonary function with forced expiratory volume at one second (FEV1), forced vital capacity (FVC) and diffusion capacity of lung 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.
  • Adequate cardiac function with left ventricular ejection fraction at least 45% on appropriate medical therapy. No uncontrolled arrhythmias or symptomatic cardiac disease.
  • Zubrod performance status <2 or Lansky/Karnofsky PS equal or greater to 70%.
Show all 9Show fewer
  • 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.
  • 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 unresolved grade >2 non-hematologic toxicity from previous therapy. Patients with grade 2 toxicity will be eligible at the discretion of the PI.
  • Patients with active central nervous system (CNS) disease.
  • Evidence of acute or chronic active hepatitis or cirrhosis.
  • Uncontrolled infection, including HIV, HTLV-1, hepatitis B or hepatitis C viremia.
  • Patients greater than 65 years-old.
  • Prior autologous or allogeneic hematopoietic stem cell transplant.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Busulfan Plus Clofarabine Followed by Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Acute Lymphoblastic Leukemia or Lymphoma, or Biphenotypic Leukemia

The goal of this clinical research study is to test the safety of giving clofarabine in combination with busulfan, followed by an allogeneic (from a donor) stem cell transplant, in patients with advanced leukemia or lymphoma.

Read the detailed description

Study Treatment:

Busulfan is designed to bind to DNA (the genetic material of cells), which may cause cancer cells to die. It is commonly used in stem cell transplants.

Clofarabine is designed to interfere with the growth and development of cancer cells.

A stem cell transplant is designed to help your body attack the cancer cells that may remain in your body after chemotherapy.

Central Venous Catheter Placement:

If you are found to be eligible to take part in this study, you will have a central venous catheter (CVC) placed. A CVC is a sterile flexible tube that will be placed into a large vein while you are under local anesthesia. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form for it.

The study drugs and stem cells will be given by vein through your CVC. The CVC will remain in your body for about 3 months.

Study Drug Administration and Stem Cell Transplant:

You will first receive a low-level "test" dose of busulfan by vein, either over 45 or 60 minutes, on Day -8 (8 days before the transplant).

A heparin lock will be placed in your vein to lower the number of needle sticks needed for the blood draws. This will involve placing an intravenous (IV) line in your lower arm that will remain in place from Day -8 through Day -6.

Blood (about 1 teaspoon each time) will be drawn for pharmacokinetic (PK) testing up to 11 times over the 11 hours after the busulfan dose on Day -8. PK testing measures the amount of study drug in the body at different time points. This PK testing will be done to find the dose of busulfan needed for your body size on the other days that you receive busulfan.

Each day from Day -6 through Day -3, you will receive clofarabine by vein over 1 hour and your body-specific dose of busulfan by vein over 3 hours. If for any reason you could not have the PK tests performed, you will receive the standard busulfan dose on these days.

The PK testing will be repeated on Day -6. Blood (about 1 teaspoon each time) will be drawn for PK testing up to 11 times over the 11 hours after the busulfan dose.

If your donor is not related to you or his/her tissue is not HLA-matched (genetically matched), you will receive antithymocyte globulin (ATG) by vein over 4 hours each day on Day -3 through Day -1. ATG is designed to weaken your immune system in order to lower the risk that your body will reject the transplant.

On Day 0, you will receive the donor's bone marrow or blood stem cells by vein. The infusion will last anywhere from about 30 minutes to several hours.

You will also receive tacrolimus and methotrexate to weaken the immune system and lower the risk of graft-versus-host disease (GVHD). GVHD is a reaction of the donor's immune cells against the recipient's body.

  • Tacrolimus will be given by vein over 24 hours every day, starting on Day -2 and continuing until you are able to take tacrolimus by mouth. Once you can take tacrolimus by mouth, you will take it every day for about 6 months. If you develop GVHD, the doctor may decide you need to take tacrolimus longer than 6 months.
  • Methotrexate will be given by vein over 15 minutes on Days 1, 3, 6, and 11 after the transplant.

Starting 1 week after the transplant, you will receive filgrastim (G-CSF) as an injection under the skin once a day until your blood cell levels return to normal.

Other Possible Treatments:

If you have a history of leukemia or lymphoma in the brain, you will receive spinal taps and chemotherapy several times over the 12 months after the transplant. The chemotherapy drug will be infused over a few minutes, during the spinal tap, directly into the space around the spinal cord. Based on standard care, the doctor will decide how often this occurs and which chemotherapy drug will be used (either methotrexate or cytarabine).

If you have a certain type of leukemia (Philadelphia chromosome positive acute lymphoblastic leukemia [ALL]), you will receive an additional drug to help prevent the cancer from returning. The drug will be imatinib mesylate or another similar type of drug that the doctor decides. It will be given by mouth, every day for up to 1 year after the transplant.

Length of Study Participation:

You will be in the hospital for about 4 weeks after the transplant. You will be taken off study if the disease gets worse. The study drugs will be stopped if intolerable side effects occur.

Follow-Up:

At 1, 3, 6, and 12 months after the transplant, the following tests and procedures will be performed:

  • Blood (about 4 tablespoons) will be drawn for routine tests.
  • You will have a bone marrow aspiration to check the status of the disease. To collect a bone marrow aspirate, an area of the hip is numbed with anesthetic, and a small amount of bone marrow is withdrawn through a large needle.
  • If the disease was not in your bone marrow at the time of diagnosis, you will have a CT and/or positron emission computed tomography (PET) scan to check the status of the disease.

The study staff will stay in contact with your local doctor to find out if the leukemia or lymphoma comes back, as well as to check how you are doing.

This is an investigational study. Busulfan and clofarabine are commercially available and FDA approved 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.

Up to 150 patients will take part in this study. All will be enrolled at M. D. Anderson.

Being tested
Busulfan, Clofarabine, Thymoglobulin, Stem Cell Transplant
Keywords
Acute Lymphoblastic Leukemia, ALL, Acute lymphoblastic lymphoma, acute biphenotypic leukemia, Allogeneic hematopoietic cell transplantation, HCT, Stem Cell Transplant, Treatment-related mortality, Tyrosine kinase inhibitors, TKI, Busulfan, Busulfex, Myleran, Clofarabine, Clolar, Clofarex, Gleevec, Imatinib Mesylate
Medical subject headings
Leukemia, Lymphoma, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Biphenotypic, Acute

What participants receive

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

  • BusulfanDrug

    Also called Busulfex, Myleran

    Test Dose 32 mg/m^2 by vein over 45 minutes on Day -8; following doses on Days -6 to -3 derived from pharmacokinetic (PK) testing done up to 11 times over 11 hours after test dose.

  • ClofarabineDrug

    Also called Clolar, Clofarex

    40 mg/m^2 by vein over 1 hour daily Day -6 through Day -3

  • ThymoglobulinDrug

    Also called Anti-thymocyte globulin, ATG

    0.5 mg/kg on Day -3, 1.5 mg/kg on Day -2 and 2.0 mg/kg on Day -1; only patients with HLA nonidentical or unrelated donors

  • Stem Cell TransplantProcedure or surgery

    Also called Allogeneic hematopoietic cell transplant, HCT

    Stem cell infusion on Day 0.

Study groups in NCT00990249
Study groupRoleWhat they receive
Busulfan + Clofarabine + Stem Cell TransplantExperimentalBusulfan test dose 32 mg/m^2 by vein over 45 minutes on Day -8; following doses on Days -6 to -3 derived from pharmacokinetic (PK) testing done up to 11 times over 11 hours after test dose. Clofarabine 40 mg/m^2 by vein over 1 hour daily Day -6 through Day -3. Thymoglobulin 0.5 mg/kg on Day -3, 1.5 mg/kg on Day -2 and 2.0 mg/kg on Day -1; only patients with HLA nonidentical or unrelated donors. Stem cell infusion on Day 0.
Receives: Drug: Busulfan; Drug: Clofarabine; Drug: Thymoglobulin; Procedure: Stem Cell Transplant

What is being measured

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

  1. Treatment-Related Mortality (TRM) Defined as Non Relapse Mortality (NRM)

    NRM was defined as death from any cause other than disease progression or relapse and reported as percentage of participant deaths. Treatment related deaths after transplant are defined either by deaths which could not be attributed to disease relapse or progression or by deaths without previous relapse or progression. For TRM at day 100, Bayesian method of Thall, Simon, and Estey used to perform interim monitoring.

    Measured: 100 Days

Timeline

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

  1. First posted6 Oct 2009 (estimated)
  2. Study startOct 2009
  3. Primary completionMay 2016
  4. Study completionMay 2016

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
120 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00990249
Sponsor's protocol ID
2009-0209
Other IDs
NCI-2012-01270
Status last verified
May 2017
First submitted
2 Oct 2009
Last updated
7 Aug 2018
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Busulfan, Clofarabine and Thymoglobulin in people with Leukemia and Lymphoma, 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 9 inclusion and 6 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 7 Aug 2018. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Aug 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Treatment-Related Mortality (TRM) Defined as Non Relapse Mortality (NRM) (time frame: 100 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 7 Aug 2018.

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