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Accelerated Phase Chronic Myelogenous LeukemiaPhase 2NCT00860574

Treosulfan, Fludarabine Phosphate, and Total-Body Irradiation Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Myelodysplastic Syndrome, Acute Lymphoblastic Leukemia

A Phase 2 study testing treosulfan, fludarabine phosphate and total-body irradiation in people with Accelerated Phase Chronic Myelogenous Leukemia and Adult Acute Lymphoblastic Leukemia in Remission, run by Fred Hutchinson Cancer Center at 3 sites 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 how well giving treosulfan together with fludarabine phosphate and total-body irradiation followed by donor stem cell transplant works in treating patients with high-risk acute myeloid leukemia, myelodysplastic syndrome, acute lymphoblastic leukemia. Read more about this study

Who is it for?
Ages Up to 60 years
What is being tested?
treosulfan, fludarabine phosphate and total-body irradiation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
96 participants
Where
3 sitesUnited States
Study dates
Feb 2009to Feb 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

  • Acute myeloid leukemia (AML):
  • All AML patients beyond 1st remission;
  • Intermediate or high risk AML patients (based on South West Oncology Group [SWOG] cytogenetic criteria) in 1st complete remission
  • Myelodysplastic syndrome (MDS)
  • Other myeloid malignancies as chronic myelogenous leukemia (CML), CML accelerated phase, CML blast crisis, chronic myelomonocytic leukemia (CMML) (to be approved by patient care conference [PCC])
  • With Karnofsky Index or Lansky Play-Performance Scale > 70% on pre-transplant evaluation
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  • Able to give informed consent (if > 18 years), or with a legal guardian capable of giving informed consent (if < 18 years)
  • Previous autologous or allogeneic HCT is allowed
  • Donors must be:
  • Human leukocyte antigen (HLA)-identical related donors or
  • Unrelated donors matched for HLA-A, B, C, DRB1, and DQB1 defined by high resolution deoxyribonucleic acid (DNA) typing or mismatched for one HLA allele, except for HLA-C where no mismatch is allowed
  • Able to undergo peripheral blood stem cell collection or bone marrow harvest
  • In good general health, with a Karnofsky or Lansky Play Performance score > 90%
  • Able to give informed consent (if > 18 years), or with a legal guardian capable of giving informed consent (if < 18 years)
  • Acute lymphoblastic leukemia (ALL): all ALL patients not eligible for other protocols

Who cannot join

  • Receiving umbilical cord blood
  • With impaired cardiac function as evidenced by ejection fraction < 35% or cardiac insufficiency requiring treatment or symptomatic coronary artery disease
  • With impaired pulmonary function as evidenced by partial pressure of oxygen (pO2) < 70 mm Hg and diffusing capacity of the lung for carbon monoxide (DLCO) < 70% of predicted or pO2 < 80 mm Hg and DLCO < 60% of predicted; or receiving supplementary continuous oxygen
  • With impaired renal function as evidenced by creatinine-clearance < 50% for age, weight, height or serum creatinine > 2x upper normal limit or dialysis-dependent
  • With hepatic dysfunction as evidenced by total bilirubin or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.0 x upper normal limit or evidence of synthetic dysfunction or severe cirrhosis
  • With active infectious disease requiring deferral of conditioning, as recommended by an Infectious Disease specialist
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  • With human immunodeficiency virus (HIV)-positivity or active infectious hepatitis because of possible risk of lethal infection when treated with immunosuppressive therapy
  • With central nervous system (CNS) leukemic involvement not clearing with intrathecal chemotherapy and/or cranial radiation prior to initiating conditioning (day -6)
  • With life expectancy severely limited by diseases other than malignancy
  • Women who are pregnant or lactating because of possible risk to the fetus or infant
  • With known hypersensitivity to treosulfan and/or fludarabine
  • Receiving another experimental drug within 4 weeks before initiation of conditioning (day -6)
  • Unable to give informed consent (if > 18 years) or with a legal guardian (if < 18 years) unable to give informed consent
  • Ineligible donors will be those:
  • Deemed unable to undergo marrow harvesting or PBSC mobilization and leukapheresis
  • Who are HIV-positive
  • With active infectious hepatitis
  • Females with a positive pregnancy test
  • Unable to give informed consent (if > 18 years) or with a legal guardian (if < 18 years) unable to give informed consent

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • University of Colorado

    Denver, Colorado, 80217-3364

  • Oregon Health and Science University

    Portland, Oregon, 97239

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

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: A Multi-Center Study of Conditioning With Treosulfan, Fludarabine and Escalating Doses of TBI for Allogeneic Hematopoietic Cell Transplantation in Patients With Acute Myeloid Leukemia (AML) Myelodysplastic Syndrome (MDS), and Acute Lymphoblastic Leukemia (ALL)

This phase II trial is studying how well giving treosulfan together with fludarabine phosphate and total-body irradiation followed by donor stem cell transplant works in treating patients with high-risk acute myeloid leukemia, myelodysplastic syndrome, acute lymphoblastic leukemia. Giving chemotherapy, such as treosulfan and fludarabine phosphate, and total-body irradiation before a donor bone marrow or 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. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus and methotrexate before and after transplant may stop this from happening

Read the detailed description

PRIMARY OBJECTIVES:

  1. Decrease the incidence of relapse to < 15% at 6 month post transplant in patients with high risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) transplanted from related or unrelated donors, without unacceptably increasing toxicity (10% non-relapse mortality [NRM] at 6 months).

SECONDARY OBJECTIVES:

  1. Evaluate the incidence of NRM at 180 days and 1 year after hematopoietic cell transplantation (HCT).

II. Evaluate overall survival (OS) and relapse-free survival (RFS). III. Incidence of grades II-IV acute graft-versus-host disease (GVHD). IV. Incidence of chronic GVHD. V. Donor chimerism on days +28 and +100.

OUTLINE:

CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -6 to day -2 and treosulfan IV over 2 hours on days -6 to day -4. Patients also undergo total-body irradiation on day 0.

TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0.

GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously or orally (PO) twice daily (BID) on days -1 to 56, followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11.

After completion of study treatment, patients are followed up periodically.

Medical subject headings
Leukemia, Myeloid, Accelerated Phase, Congenital Abnormalities, Blast Crisis, Leukemia, Myelomonocytic, Chronic, 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.

  • treosulfanDrug

    Also called dihydroxybusulfan, Ovastat, tresulfon

    Given IV

  • fludarabine phosphateDrug

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

    Given IV

  • total-body irradiationRadiation

    Also called TBI

    Low dose starting at 2Gy

  • peripheral blood stem cell transplantationProcedure or surgery

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

    Given IV per institutional standard practice

  • tacrolimusDrug

    Also called FK 506, Prograf

    Given IV or PO

  • allogeneic bone marrow transplantationProcedure or surgery

    Also called bone marrow therapy, allogeneic, bone marrow therapy, allogenic, transplantation, allogeneic bone marrow, transplantation, allogenic bone marrow

    Given IV per institutional standard practice

  • allogeneic hematopoietic stem cell transplantationProcedure or surgery

    Given IV per institutional standard practice

  • methotrexateDrug

    Also called amethopterin, Folex, methylaminopterin, Mexate

    Given IV

Study groups in NCT00860574
Study groupRoleWhat they receive
Treatment (allogeneic transplantation)ExperimentalCONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to day -2 and treosulfan IV over 2 hours on days -6 to day -4. Patients also undergo total-body irradiation on day 0. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously or PO BID on days -1 to 56, followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
Receives: Drug: treosulfan; Drug: fludarabine phosphate; Radiation: total-body irradiation; Procedure: peripheral blood stem cell transplantation; Drug: tacrolimus; Procedure: allogeneic bone marrow transplantation; Procedure: allogeneic hematopoietic stem cell transplantation; Drug: methotrexate

What is being measured

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

  1. Relapse Incidence

    Measured: At 6 months

  2. Non Relapse Mortality (NRM) Incidence

    Cumulative incidence of NRM at 6 months. NRM includes all deaths without relapse or disease progression.

    Measured: At 6 months

Secondary outcomes (6)

  1. Non Relapse Mortality Incidence

    Measured: 1 year after HCT

  2. Overall Survival (OS)

    Measured: at 2 years

  3. Relapse-free Survival

    Measured: at 2 years

  4. Incidence of Grades II-IV Acute GVHD

    Measured: at 6 months

  5. Incidence of Chronic GVHD

    Measured: at 6 months

  6. Median Donor CD3 + T Lymphocyte Chimerism in Peripheral Blood

    Donor chimerism was evaluated in peripheral blood T cells

    Measured: Day 28 after HCT

Timeline

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

  1. First posted12 Mar 2009 (estimated)
  2. Study startFeb 2009
  3. Primary completionFeb 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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
96 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00860574
Sponsor's protocol ID
2272.00
Other IDs
NCI-2010-00315, P01HL036444
Status last verified
Feb 2021
First submitted
11 Mar 2009
Last updated
22 Jun 2021
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing treosulfan, fludarabine phosphate and total-body irradiation in people with Accelerated Phase Chronic Myelogenous Leukemia and Adult Acute Lymphoblastic Leukemia in Remission, run by Fred Hutchinson Cancer Center at 3 sites 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 15 inclusion and 19 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 22 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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 Feb 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?

Relapse Incidence (time frame: At 6 months). The study lists 2 primary outcomes in all. 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 NCT00860574.

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 22 Jun 2021.

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