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Acute Myeloid LeukemiaPhase 2NCT00469014

Busulfan, Fludarabine, Clofarabine With Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia

A Phase 2 study testing Clofarabine, Busulfan and Fludarabine in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome, 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 find the best dose of clofarabine and fludarabine that can be given with busulfan followed by an allogeneic blood stem cell transplant. Researchers will study whether this combination can help to control the disease, and look at the safety of this combination. Read more about this study

Who is it for?
Ages Up to 60 years
What is being tested?
Clofarabine, Busulfan and Fludarabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
72 participants
Where
1 siteUnited States
Study dates
Sep 2006to Mar 2013
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 60 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Diagnosis or 1) Acute myeloid leukemia past first remission, in first or subsequent relapse, or induction failures, 2) Myelodysplastic syndromes with intermediate or high risk International Prognostic Scoring System score (IPSS scores) (16), and having failed previous chemotherapy, or 3) Chronic Myeloid Leukemia, Philadelphia-chromosome positive and having failed / being resistant to therapy based on Gleevec or other tyrosine kinase inhibitors.
  • Patient has not been administered intensive systemic chemotherapeutic drugs within 21 days prior to trial enrollment (bone marrow transplant (BMT) Day -9). Gleevec, alternative tyrosine kinase inhibitors, other nonmyelosuppressive agents, low dose cytarabine, hydroxyurea is permitted if indicated to control the leukemia. All tyrosine inhibitor- or other non-myelosuppressive agents have to be terminated at least one week prior to admission for this treatment.
  • No uncontrolled infection. Protocol principal investigator (PI) will be final arbiter if there is uncertainty regarding whether a previous infection is resolved on appropriate antibiotics therapy.
  • age </= 60
  • A related or unrelated donor who is HLA-matched or mismatched in 1 HLA, A, B, C, DR or DQ locus is acceptable (i.e. at least a 9/10 matched related or unrelated donor, matched with molecular high-resolution technique per current standard for the BMT program).
  • ZUBROD performance status <2
Show all 13Show fewer
  • Life expectancy is not severely limited by concomitant illness.
  • Left ventricular ejection fraction >/=45% No uncontrolled arrhythmias or symptomatic cardiac disease.
  • Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and carbon monoxide diffusing capacity (DLCO) >/= 50% of expected corrected for hemoglobin. In patients </= 7 years pulmonary function will be assessed per pediatric BMT routine
  • Serum creatinine </= 1.5 mg%.
  • Serum glutamic pyruvic transaminase (SGPT) </= 200 IU/ml, serum bilirubin and alkaline phosphatase within accepted laboratory standard normal limits or considered not clinically significant. No evidence of chronic active hepatitis or cirrhosis. If positive hepatitis serology, discuss with Study Chairman and perform liver biopsy pror to determining study eligibility.
  • Female patient is not pregnant (negative human chorionic gonadotropin (hCG) pregnancy test in all women of child-bearing-potential in accordance with departmental routine).
  • Patient or patient's legal representative, parent(s) or guardian able to sign informed consent.

Who cannot join

  • Effusion or ascites estimated to be >1L prior to drainage.
  • HIV-positive.
  • Hepatitis C or HBsAg positive
  • Prior stem cell transplant after a myeloablative conditioning program (such as busulfan-based using a total dose of >/= 12 mg/kg given by mouth or >/= 10 mg/kg IV, or a total-body irradiation-based program.
  • Active or prior Central Nervous System (CNS) leukemia
  • Biphenotypic acute leukemia.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • UT MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Busulfan-Fludarabine-Clofarabine With Allogeneic Stem Cell Transplantation for Advanced Refractory Acute Myeloid Leukemia, Myelodysplastic Syndrome, and Advanced, Gleevec Refractory Chronic Myeloid Leukemia. A Randomized Phase II Study.

The goal of this clinical research study is to find the best dose of clofarabine and fludarabine that can be given with busulfan followed by an allogeneic blood stem cell transplant. Researchers will study whether this combination can help to control the disease, and look at the safety of this combination. Researchers also want to find out if combining busulfan with clofarabine alone or combining busulfan with both fludarabine and clofarabine will improve the treatment, compared with the previous standard method using busulfan and fludarabine alone.

Read the detailed description

Busulfan is a chemotherapy drug that kills cancer cells by binding to DNA (the genetic material of cells). Clofarabine is designed to interfere with the growth and development of cancer cells. Fludarabine is designed to interfere with DNA repair enzymes so that the leukemic cells cannot repair damaged DNA. This may increase the likelihood of the cell dying. These drugs are being given to try to kill cancerous cells and weaken your immune system in order to lower the risk of stem cell transplant rejection.

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to 1 of 4 study groups. Three (3) of the groups will receive busulfan, fludarabine, and clofarabine at different dose levels. The 4th group will only receive busulfan and clofarabine. As the study continues, participants will be assigned using a method called adaptive randomization. This method works by increasing the chances of being assigned to the group that has had the best results in the study so far. You will know which group you have been assigned to.

Participants will receive busulfan, fludarabine, and/or clofarabine once a day for 4 doses. You will first receive an additional low-level "test" dose of busulfan given by vein to check how your blood levels change over time. This information will be used to decide the next dose needed to reach a target blood level of busulfan. You will have a total of about 6 and 1/2 tablespoons of blood drawn over time to check your busulfan blood levels following one or more of the busulfan treatments. Up to 11 samples of blood will be drawn to check your blood levels of busulfan during the next 11 hours following the test dose and the first high-dose busulfan treatment. Each sample will require about 1 teaspoon of blood. A heparin lock line will be placed in a vein to lower the number of needle sticks needed for these draws. If it is not possible for these blood level tests to be performed for technical or scheduling reasons, you will receive the standard fixed (unchanging) dose of busulfan.

Clofarabine and fludarabine (if applicable) will be given through a central venous catheter (CVC) over 1 hour, once a day, for 4 days. Busulfan will also be given through the CVC over 3 hours.

If you are going to be receiving a transplant from an HLA-nonidentical or unrelated donor, you will also receive thymoglobulin (ATG) over 4 hours on the 3 days before the transplant to further weaken your immune system to reduce the risk of rejecting of the transplant. After the transplant, you will receive tacrolimus, methotrexate, or other immunosuppressive (lowering the immune system) drugs in the standard manner to lower the risk of graft-vs-host disease (GVHD), a reaction of the donor's immune cells against the recipient's body.

The allogeneic stem cells (bone marrow or peripheral blood stem cells) will also be given through the CVC. You will receive the drug G-CSF (filgrastim) as an injection under the skin once a day, starting 1 week after the transplant, until your blood cell levels return to normal.

Patients usually stay in the hospital for about 4 weeks after stem cell transplantation. After you are released from the hospital, you will continue to be monitored as an outpatient for infections and transplant-related complications for at least 100 days after the transplant.

You will have blood tests (about 4 tablespoons of blood) and bone marrow aspirations performed at 1, 3, 6, and 12 months after the transplant, to check if the disease is in remission (has not come back). Your health status will be followed with the help of your local doctor to find out if the leukemia or MDS comes back, as well as to check the length of your survival.

This is an investigational study. All of the drugs used in this study are approved by the FDA for treatment of cancer. Busulfan has been approved for use in stem cell transplantation. The use of these drugs together with stem cell transplant is experimental. Up to 70 patients will take part in this study. All will be enrolled at the M. D. Anderson Cancer Center.

Being tested
Clofarabine, Busulfan, Fludarabine, Stem Cell Infusion, Thymoglobulin (ATG)
Keywords
Acute Myeloid Leukemia, AML, Myelodysplastic Syndrome, MDS, Chronic Myeloid Leukemia, CML, Busulfan, Busulfex, Myleran, Fludarabine, Fludara, Fludarabine Phosphate, Clofarabine, Clofarex, Clolar, Allogeneic stem cell transplantation, ASCT, Stem Cell, Gleevec, Imatinib Mesylate
Medical subject headings
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Leukemia, Myelogenous, Chronic, BCR-ABL Positive

What participants receive

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

  • ClofarabineDrug

    Also called Clofarex, Clolar

    Day -6 to Day -3 for Arm 1 = 10 mg/m^2 intravenous (IV) Daily; Arm 2 = 20 mg/m^2 IV Daily; Arm 3 = 30 mg/m^2 IV Daily; Arm 4 = 40 mg/m^2 IV Daily

  • BusulfanDrug

    Also called Busulfex, Myleran

    Day -6 to Day -3 for Arm 1: 30 mg/m^2 IV Daily; Arm 2: 20 mg/m^2 IV Daily; Arm 3: 10 mg/m^2 IV Daily; Arm 4: 40 mg/m^2 IV Daily.

    Test dose Day -8 32 mg/ m^2 IV over 45 min, rest on Day -7.

  • FludarabineDrug

    Also called Fludarabine Phosphate, Fludara

    Day -6 to Day -3 for Arm 1: 30 mg/m^2 IV Daily; Arm 2: 20 mg/m^2 IV Daily; Arm 3: 10 mg/m^2 IV Daily

  • Stem Cell InfusionOther

    Also called Bone Marrow Transplant, BMT, peripheral blood progenitor cells, PBPC

    Day 0 stem cell infusion (Bone marrow or peripheral blood progenitor cells (PBPC))

  • Thymoglobulin (ATG)Drug

    Also called Thymoglobulin, Antithymocyte Globulin

    Day -3 to Day -1 at 0.5 mg/kg IV on Day -3; 1.5 mg/kg on Day -2 and 2.0 mg/kg on Day -1.

  • FilgrastimDrug

    Also called G-CSF, Granulocyte colony-stimulating factor, GCSF

    Subcutaneous injection daily, starting 1 week after Stem Cell Transplant.

Study groups in NCT00469014
Study groupRoleWhat they receive
Arm 1: Busulfan + Fludarabine (30 mg/m^2) + ClofarabineActive comparator4-day Treatment Period Day -6 to Day -2: Busulfan 30 mg/m^2 intravenous (IV) Daily + Fludarabine 30 mg/m^2 IV Daily; + Clofarabine 10 mg/m^2 IV Daily; Thymoglobulin Day -3 to Day -1, and Stem Cell Infusion Day 0.
Receives: Drug: Clofarabine; Drug: Busulfan; Drug: Fludarabine; Other: Stem Cell Infusion; Drug: Thymoglobulin (ATG); Drug: Filgrastim
Arm 2: Busulfan + Fludarabine (20 mg/m^2) + ClofarabineExperimental4-day Treatment Period Day -6 to Day -2: Busulfan 20 mg/m^2 IV + Fludarabine 20 mg/m^2 IV Daily + Clofarabine 20 mg/m^2 IV Daily. Thymoglobulin Day -3 to Day -1, and Stem Cell Infusion Day 0.
Receives: Drug: Clofarabine; Drug: Busulfan; Drug: Fludarabine; Other: Stem Cell Infusion; Drug: Thymoglobulin (ATG); Drug: Filgrastim
Arm 3: Busulfan + Fludarabine (10 mg/m^2) + ClofarabineExperimental4-day Treatment Period Day -6 to Day -2: Busulfan 10 mg/m^2 IV Daily + Fludarabine 10 mg/m^2 IV Daily + Clofarabine 30 mg/m^2 IV Daily. Thymoglobulin Day -3 to Day -1, and Stem Cell Infusion Day 0.
Receives: Drug: Clofarabine; Drug: Busulfan; Drug: Fludarabine; Other: Stem Cell Infusion; Drug: Thymoglobulin (ATG); Drug: Filgrastim
Arm 4: Busulfan + ClofarabineExperimental4-day Treatment Period Day -6 to Day -2: Busulfan 40 mg/m^2 IV Daily + Clofarabine 40 mg/m^2 IV Daily. Thymoglobulin Day -3 to Day -1, and Stem Cell Infusion Day 0.
Receives: Drug: Clofarabine; Drug: Busulfan; Other: Stem Cell Infusion; Drug: Thymoglobulin (ATG); Drug: Filgrastim

What is being measured

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

  1. Treatment Related Mortality

    Number of participants with treatment related mortality (death) within the first 30 days following transplantation.

    Measured: First 30 Days

Timeline

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

  1. First posted4 May 2007 (estimated)
  2. Study startSep 2006
  3. Primary completionMar 2013
  4. Study completionMar 2013

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
72 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00469014
Sponsor's protocol ID
2006-0200
Status last verified
Jan 2021
First submitted
3 May 2007
Last updated
26 Jan 2021
Data monitoring committee
Yes

Publications

  • Andersson BS, Valdez BC, de Lima M, Wang X, Thall PF, Worth LL, Popat U, Madden T, Hosing C, Alousi A, Rondon G, Kebriaei P, Shpall EJ, Jones RB, Champlin RE. Clofarabine +/- fludarabine with once daily i.v. busulfan as pretransplant conditioning therapy for advanced myeloid leukemia and MDS. Biol Blood Marrow Transplant. 2011 Jun;17(6):893-900. doi: 10.1016/j.bbmt.2010.09.022. Epub 2010 Oct 11.

    PubMed 20946966

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Clofarabine, Busulfan and Fludarabine in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome, 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 13 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 26 Jan 2021. 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 26 Jan 2021). 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 (time frame: First 30 Days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00469014, which also lists 1 linked publication.

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 26 Jan 2021.

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