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Accelerated Phase Chronic Myelogenous LeukemiaPhase 2NCT01056614

Fludarabine Phosphate, Busulfan, and Anti-Thymocyte Globulin Followed By Donor Peripheral Blood Stem Cell Transplant, Tacrolimus, and Methotrexate in Treating Patients With Myeloid Malignancies

A Phase 2 study testing fludarabine phosphate, busulfan and anti-thymocyte globulin in people with Accelerated Phase Chronic Myelogenous Leukemia and Adult Acute Myeloid Leukemia in Remission, run by Fred Hutchinson 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 II trial is studying the side effects and how well giving fludarabine phosphate, busulfan, anti-thymocyte globulin followed by donor peripheral blood stem cell transplant, tacrolimus, and methotrexate works in treating patients with myeloid malignancies. Read more about this study

Who is it for?
Ages Up to 60 years
What is being tested?
fludarabine phosphate, busulfan and anti-thymocyte globulin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
23 participants
Where
1 siteUnited States
Study dates
Sep 2004to Apr 2016
Phase
Phase 2
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

  • Chronic myelogenous leukemia in chronic phase, accelerated phase and treated blast phase (CP2)
  • Acute myeloid leukemia (AML) in remission or early relapse (< 10% marrow blasts)
  • Myelodysplastic syndromes (MDS) ( all risk groups)
  • Other myeloproliferative disorders
  • DONOR: related or unrelated donors matched for human leukocyte antigen (HLA)-A, B, C, DRB1, and DQB1 defined by high resolution deoxyribonucleic acid (DNA) typing or mismatched for a single HLA-A, B, C, DRB1 or DQB1 allele
  • DONOR: donor must consent to peripheral blood stem cell (PBSC) mobilization with granulocyte colony-stimulating factor (G-CSF) and leukapheresis; related donors will be collected at Fred Hutchinson Cancer Research Center (FHCRC), while unrelated donors will be collected through the National Marrow Donor Program (NMDP) or other donor centers
  • DONOR: Age 12-75 yrs

Who cannot join

  • Cardiac insufficiency requiring treatment or symptomatic coronary artery disease
  • Hepatic disease, with aspartate aminotransferase (AST) > 2 times normal
  • Severe hypoxemia, oxygen partial pressure (pO2) < 70 mm Hg, with decreased diffusion capacity of carbon monoxide (DLCO) < 70% of predicted; or mild hypoxemia, pO2 < 80 mm Hg with severely decreased DLCO < 60% of predicted
  • Impaired renal function (creatinine > 2 times normal or estimated creatinine clearance < 60 ml/min)
  • MALE: ([140 -age in years] x ideal body weight [kg])/72 x serum creatinine (SCr) (mg/dL)
  • FEMALE: .85 x ([140-age in years] x ideal body weight [kg])/72 x SCr (mg/dL)
Show all 12Show fewer
  • Human immunodeficiency virus (HIV)-positive patients due to risk of reactivation or acceleration of HIV replication
  • Female patients who are pregnant or breast feeding
  • Life expectancy severely limited by diseases other than malignancy
  • DONOR: donors who for any reason are unable to tolerate the mobilization and leukapheresis procedure
  • DONOR: donors who are HIV-positive, or hepatitis B or C antigen-positive
  • DONOR: female donors who have a positive pregnancy test

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: Conditioning for Hematopoietic Cell Transplantation With Fludarabine Plus Targeted IV Busulfan and GVHD Prophylaxis With Thymoglobulin, Tacrolimus and Methotrexate in Patients With Myeloid Malignancies

This phase II trial is studying the side effects and how well giving fludarabine phosphate, busulfan, anti-thymocyte globulin followed by donor peripheral blood stem cell transplant, tacrolimus, and methotrexate works in treating patients with myeloid malignancies. Giving chemotherapy, such as fludarabine phosphate and busulfan, before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving anti-thymocyte globulin before transplant and tacrolimus and methotrexate after transplant may stop this from happening.

Read the detailed description

PRIMARY OBJECTIVE:

  1. Determine the incidence and severity of acute graft-versus-host disease (GvHD).

SECONDARY OBJECTIVES:

  1. Determine the pharmacokinetics of intravenous (IV) busulfan including interdose variability and evaluation of a limited sampling strategy.

II. Determine thymoglobulin (anti-thymocyte globulin) pharmacokinetics.

III. Determine the incidence of donor engraftment.

IV. Determine system toxicities >= grade 3 per Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 3.

  1. Determine the incidence and severity of chronic GvHD.

VI. Determine the incidence of non-relapse mortality at day +100 and at 1 year (yr).

VII. Determine the incidence of relapse.

VIII. Determine relapse-free survival.

IX. Determine the incidence of Epstein-Barr virus (EBV) activation.

OUTLINE:

Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -9 to -6, busulfan IV over 3 hours on days -5 to -2, and anti-thymocyte globulin IV over 6 hours on days -3 and -2 and over 4 hours on day -1. Patients undergo allogeneic peripheral blood stem cell (PBSC) transplant on day 0. Patients then receive tacrolimus IV continuously or orally (PO) every 12 hours beginning on day -1 and taper to day 180 and methotrexate IV on days 1, 3, 6, and 11.

After completion of study treatment, patients are followed at 1 year.

Being tested
fludarabine phosphate, busulfan, anti-thymocyte globulin, tacrolimus, methotrexate
Medical subject headings
Leukemia, Myeloid, Accelerated Phase, Congenital Abnormalities, Blast Crisis, Leukemia, Myeloid, Chronic-Phase, Hematologic Neoplasms, Myeloproliferative Disorders, Leukemia, Myeloid, Acute

What participants receive

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

  • fludarabine phosphateDrug

    Also called 2-F-ara-AMP, Beneflur, Fludara

    Given IV

  • busulfanDrug

    Also called BSF, BU, Misulfan, Mitosan

    Given IV

  • anti-thymocyte globulinBiological

    Also called ATG, ATGAM, lymphocyte immune globulin, Thymoglobulin

    Given IV

  • tacrolimusDrug

    Also called FK 506, Prograf

    Given IV and orally

  • methotrexateDrug

    Also called amethopterin, Folex, methylaminopterin, Mexate

    Given IV

  • peripheral blood stem cell transplantationProcedure or surgery

    Also called PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell

    Undergo allogeneic PBSC transplant

  • allogeneic hematopoietic stem cell transplantationProcedure or surgery

    Undergo allogeneic PBSC transplant

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT01056614
Study groupRoleWhat they receive
Treatment (chemotherapy, PBSC transplant)ExperimentalPatients receive fludarabine phosphate IV over 30 minutes on days -9 to -6, busulfan IV over 3 hours on days -5 to -2, and anti-thymocyte globulin IV over 6 hours on days -3 and -2 and over 4 hours on day -1. Patients undergo allogeneic PBSC transplant on day 0. Patients then receive tacrolimus IV continuously or PO every 12 hours beginning on day -1 and taper to day 180 and methotrexate IV on days 1, 3, 6, and 11.
Receives: Drug: fludarabine phosphate; Drug: busulfan; Biological: anti-thymocyte globulin; Drug: tacrolimus; Drug: methotrexate; Procedure: peripheral blood stem cell transplantation; Procedure: allogeneic hematopoietic stem cell transplantation; Other: laboratory biomarker analysis

What is being measured

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

  1. Incidence of acute GvHD

    Maximum grade of acute GVHD and the number of therapies required to treat GVHD will be determined.

    Measured: Day 100 post-transplant

Secondary outcomes (10)

  1. Pharmacokinetics of IV busulfan including interdose variability and evaluation of a limited sampling strategy

    Measured: At 3.25, 4.5, 6, 8, 11, and 24-hours after the beginning of infusion on days -5, -4, and -3

  2. Thymoglobulin pharmacokinetics

    Measured: On day -3 prior to the first dose, on day -1 one hour after completion of infusion and on day 1 at 0900

  3. Incidence of donor cell engraftment

    Measured: By day 100

  4. Incidence of system toxicities >= grade 3 as graded per CTCAE v.3

    Measured: Up to day 100 after transplantation

  5. Incidence of chronic GvHD

    Measured: Day 100

  6. Incidence of non-relapse mortality defined as death without history of post-transplant relapse

    Measured: At day 100

  7. Incidence of non-relapse mortality defined as death without history of post-transplant relapse

    Measured: At 1 year

  8. Incidence of relapse

    Defined by either morphological or cytogenetic evidence of chronic myelogenous leukemia (CML), AML, MDS or other myeloproliferative disease in marrow, blood, or other sites, or laboratory evidence of residual disease.

    Measured: At 1 year

  9. Relapse-free survival

    Measured: At 1 year

  10. Incidence of EBV activation defined as an increase in plasma EBV DNA to >= 1000 copies/mL as determined by quantitative polymerase chain reaction (PCR)

    Measured: Up to 1 year

Timeline

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

  1. First posted26 Jan 2010 (estimated)
  2. Study startSep 2004
  3. Primary completionAug 2005
  4. Study completionApr 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
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01056614
Sponsor's protocol ID
1913.00
Other IDs
NCI-2009-01785, 1913.00, P30CA015704, P01HL036444
Status last verified
May 2016
First submitted
22 Jan 2010
Last updated
6 May 2016
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing fludarabine phosphate, busulfan and anti-thymocyte globulin in people with Accelerated Phase Chronic Myelogenous Leukemia and Adult Acute Myeloid Leukemia in Remission, run by Fred Hutchinson 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 7 inclusion and 12 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 May 2016. 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?

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?

Incidence of acute GvHD (time frame: Day 100 post-transplant). 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 NCT01056614.

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 May 2016.

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