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LeukemiaPhase 2NCT00392782

Donor Stem Cell Transplant in Treating Patients With Myeloid Cancer or Other Disease

A Phase 2 study testing anti-thymocyte globulin, fludarabine phosphate and thiotepa in people with Leukemia and Myelodysplastic Syndromes, run by Masonic Cancer Center, University of Minnesota at 9 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

RATIONALE: Giving total-body irradiation and chemotherapy, such as fludarabine and thiotepa, before a donor stem cell transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. Read more about this study

Who is it for?
Ages Up to 60 years
Conditions the study is for
Leukemia, Myelodysplastic Syndromes
What is being tested?
anti-thymocyte globulin, fludarabine phosphate and thiotepa
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
9 sitesUnited States
Study dates
Jul 2005to May 2011
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

  • Primary acute myeloid leukemia (AML)
  • First complete remission (CR) with high risk features as defined by: failure to achieve remission by day 21 after induction chemotherapy, or the presence of chromosomal abnormalities involving any of the following: -5/de (5q), -7/del(7q), inversion 3q, abnormalities of 11q23, 20q, 21q, del(9q), translocation 6;9, translocation 9;22, abnormalities of 17p, or complex karyotype with > or = 3 abnormalities. Complete remission is defined as < 5% blasts in the marrow.
  • Second CR or subsequent in remission
  • Refractory or relapsed disease with absolute peripheral blood blasts < 2000/mcL
  • Secondary AML in remission or relapse
  • Chronic myelogenous leukemia (CML) in accelerated or blast phase
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  • Accelerated phase is defined by any one of the following:
  • Blasts 10% to 19% of peripheral blood white cells or bone marrow cells
  • Peripheral blood basophils at least 20%
  • Persistent thrombocytopenia (<100 x 10^9/L) unrelated to therapy, or persistent thrombocytosis (>1000 x 10^9/L) unresponsive to therapy
  • Increasing spleen size and increasing white blood cell (WBC) count unresponsive to therapy
  • Cytogenetic evidence of clonal evolution (i.e., the appearance of an additional genetic abnormality that was not present in the initial specimen at the time of diagnosis of chronic phase CML)
  • Resistance to tyrosine kinase inhibitors (imatinib or other) defined as no complete cytogenetic response even if the above criteria are not met.
  • Blast phase is defined by either of the following:
  • Blasts 20% or more of peripheral blood white cells or bone marrow cells
  • Extramedullary blast proliferation
  • Large foci or clusters of blasts in bone marrow biopsy
  • Primary myelodysplastic syndrome (MDS) with an IPSS score >1
  • Secondary MDS with any international prostate symptom score (IPSS)
  • Age ≤60 years
  • Co-Morbidity score 0-2
  • At least 35 days following start of preceding leukemia induction therapy

Who cannot join

  • Patients for whom a suitable HLA genotypically identical sibling or fully matched HLA-A, -B, -C, and -DRB1 unrelated donor is available.
  • Patients greater than 60 years of age.
  • Hypersensitivity to thymoglobulin.
  • Symptomatic uncontrolled coronary artery disease or congestive heart failure.
  • Hepatic disease with transaminases or bilirubin > 2 times upper limit of normal (ULN) except for isolated hyperbilirubinemia attributed to Gilbert's syndrome.
  • Severe hypoxemia with room air - Partial Pressure of Oxygen in Arterial Blood - (PAO2) < 70, supplemental oxygen-dependence, or carbon monoxide diffusing capacity (DLCO) < 50% predicted.
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  • Impaired renal function with creatinine > 2 times upper limit of normal (ULN) or creatinine clearance measured by 24-hour urine collection < 50% normal for age, gender, and weight.
  • Patients with central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy.
  • Patients who are human immunodeficiency virus (HIV) seropositive.
  • Patients who are pregnant or breast-feeding.
  • Patients with active infections that are untreated, or failing to respond to appropriate therapy.
  • Karnofsky performance status < 50%.
  • Prior allogeneic or autologous bone marrow, peripheral blood stem cell, or umbilical cord blood transplant.
  • Inability to provide informed consent.
  • Co-morbidity score >2
  • Less than 35 days from start of previous leukemia induction therapy

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

United States9 sites

  • Winship Cancer Institute of Emory University

    Atlanta, Georgia, 30322

  • Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210-1240

  • Indiana University Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202-5289

  • Medical College of Wisconsin Cancer Center

    Milwaukee, Wisconsin, 53226

  • Midwest Children's Cancer Center at Children's Hospital of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Masonic Cancer Center at University of Minnesota

    Minneapolis, Minnesota, 55455

  • Abramson Cancer Center of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104-4283

  • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

    St Louis, Missouri, 63110

  • Moffitt Cancer Center

    Tampa, Florida, 33612

Other trials in United States

About this study

Official title: A Multicenter, Prospective Trial to Evaluate the Role of NK Cell KIR Epitope Mismatch on Mortality and Disease Relapse in T-Cell Depleted Hematopoietic Stem Cell Transplantation From HLA-C Mismatched, Unrelated Donors for Myeloid Malignancies

RATIONALE: Giving total-body irradiation and chemotherapy, such as fludarabine and thiotepa, before a donor stem cell transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When 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 antithymocyte globulin and removing the T cells from the donor cells before transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well a donor stem cell transplant works in treating patients with myeloid cancer or other disease.

Read the detailed description

OBJECTIVES:

Primary

  • Determine the incidence of disease-free survival at 1 year in patients with acute or chronic myeloid leukemias undergoing T-cell-depleted hematopoietic stem cell transplantation from HLA-C mismatched, unrelated donors.

Secondary

  • Determine the incidence of disease relapse at 1 year in patients treated with this regimen.
  • Determine the incidence and severity of acute graft-vs-host disease (GVHD) at 100 days and chronic GVHD at 1 year in these patients.
  • Determine the incidence of graft failure at day 100.
  • Determine the transplant-related mortality of these patients at 1 year.
  • Determine the overall survival of these patients at 1 year.

OUTLINE: This is a prospective, multicenter study. Patients are stratified according to killer-cell immunoglobulin-like receptors (KIR) epitope mismatch (yes [experimental] vs no [control]).

  • Myeloablative preparative regimen: Patients undergo total body irradiation twice daily on days -10 and -9 and receive thiotepa intravenously (IV) over 4 hours on days -8 and -7, fludarabine phosphate IV over 30-60 minutes on days -7 to -3, and antithymocyte globulin IV over 4-6 hours on days -5 to -2.
  • Allogeneic peripheral blood stem cell (PBSC) transplantation: Patients undergo filgrastim (G-CSF)-mobilized, T-cell-depleted, CD34+-selected allogeneic PBSC transplantation on day 0.

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

Keywords
adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia in remission, childhood acute myeloid leukemia in remission, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), recurrent adult acute myeloid leukemia, recurrent childhood acute myeloid leukemia, secondary acute myeloid leukemia, accelerated phase chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia, childhood chronic myelogenous leukemia, relapsing chronic myelogenous leukemia, secondary myelodysplastic syndromes
Medical subject headings
Leukemia, Myelodysplastic Syndromes, Congenital Abnormalities, Leukemia, Myeloid, Acute, Leukemia, Myeloid, Accelerated Phase, Blast Crisis

What participants receive

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

  • anti-thymocyte globulinBiological

    Also called ATG

    Rabbit thymoglobulin will be given intravenously at a dose of 2.5 mg/kg on days -5,-4, -3, and -2. The first dose of thymoglobulin will be given over six (6) hours and subsequent doses over four (4) or more hours as tolerated or, per institutional anti-thymocyte globulin (ATG) administration guidelines.

  • fludarabine phosphateDrug

    Also called Fludara

    Fludarabine 40 mg/m^2/day intravenously (IV) over 30-60 minutes on days -7,-6,-5,-4,-3 (total dose 200 mg/m^2).

  • thiotepaDrug

    Thiotepa 5 mg/kg/day intravenously (IV) over 4 hours on days -8, -7 (total dose 10 mg/kg).

  • peripheral blood stem cell transplantationProcedure or surgery

    Also called PBSC

    Peripheral Blood Stem Cell (PBSC) Infusion. All patients will receive granulocyte colony-stimulating factor (G-CSF)-mobilized PBSC on day 0 (or day+1 when available) following CD34 cell selection for ex vivo T cell removal. PBSC is infused via a central venous catheter using blood infusion tubing.

  • total-body irradiationRadiation

    Also called TBI

    The total-body irradiation (TBI) will be given in 2 fractions of 400 cGy each administered on day -10 and -9 via anterior and posterior fields for a total dose of 800 cGy.

Study groups in NCT00392782
Study groupRoleWhat they receive
Natural Killer Cell Kir EpitopeExperimentalNot described
Receives: Biological: anti-thymocyte globulin; Drug: fludarabine phosphate; Drug: thiotepa; Procedure: peripheral blood stem cell transplantation; Radiation: total-body irradiation

What is being measured

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

  1. Incidence of Disease-free Survival

    Number of patients alive and without disease at 1 year after transplant.

    Measured: 1 Year

Secondary outcomes (6)

  1. Incidence of Disease Relapse

    Number of patients with disease at 1 year.

    Measured: 1 Year

  2. Incidence of Grade II-IV Acute Graft-vs-host Disease (GVHD)

    Number of patients with grade II-IV acute graft-versus-host disease at Day 100 post transplant. Graft-versus-host disease (GVHD) is a common complication of allogeneic bone marrow transplantation in which functional immune cells in the transplanted marrow recognize the recipient as "foreign" and mount an immunologic attack. Grade I=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening.

    Measured: Day 100

  3. Incidence of Chronic Graft-versus-host Disease (GVHD)

    Number of patients with chronic graft-versus-host disease at 1 year post transplant. Graft-versus-host disease (GVHD) is a common complication of allogeneic bone marrow transplantation in which functional immune cells in the transplanted marrow recognize the recipient as "foreign" and mount an immunologic attack. Grade I=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening. Chronic GVHD is an extension of acute GVHD.

    Measured: 1 Year

  4. Incidence of Graft Failure

    Number of patients with graft failure is defined by lack of neutrophil engraftment by 100 days after transplant in patients surviving a minimum of 14 days.

    Measured: Day 100

  5. Transplant-related Mortality

    Number of patients with treatment related death at 1 year post transplant.

    Measured: 1 Year

  6. Overall Survival

    Number of patients who were deceased at 1 year post transplant.

    Measured: 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 Oct 2006 (estimated)
  2. Study startJul 2005
  3. Primary completionMay 2011
  4. Study completionMay 2011

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
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00392782
Sponsor's protocol ID
2004UC035
Other IDs
UMN-MT2004-04, UMN-0405M59662
Status last verified
Dec 2017
First submitted
25 Oct 2006
Last updated
28 Dec 2017
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing anti-thymocyte globulin, fludarabine phosphate and thiotepa in people with Leukemia and Myelodysplastic Syndromes, run by Masonic Cancer Center, University of Minnesota at 9 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 22 inclusion and 16 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: stopped early, as of the sponsor's last update on 28 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 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 15 Jul 2011). 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?

Incidence of Disease-free Survival (time frame: 1 Year). 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 NCT00392782.

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 28 Dec 2017.

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