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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT01056614
Other study ID # 1913.00
Secondary ID NCI-2009-0178519
Status Active, not recruiting
Phase Phase 2
First received January 22, 2010
Last updated November 3, 2015
Start date September 2004

Study information

Verified date November 2015
Source Fred Hutchinson Cancer Research Center
Contact n/a
Is FDA regulated No
Health authority United States: Federal Government
Study type Interventional

Clinical 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. 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.


Description:

PRIMARY OBJECTIVE:

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

SECONDARY OBJECTIVES:

I. 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.

V. 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.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 23
Est. completion date
Est. primary completion date August 2005
Accepts healthy volunteers No
Gender Both
Age group N/A to 60 Years
Eligibility Inclusion Criteria:

- 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

Exclusion Criteria:

- 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)

- 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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms

  • Accelerated Phase Chronic Myelogenous Leukemia
  • Adult Acute Myeloid Leukemia in Remission
  • Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
  • Adult Acute Myeloid Leukemia With Del(5q)
  • 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)
  • Blast Crisis
  • Blastic Phase Chronic Myelogenous Leukemia
  • Childhood Acute Myeloid Leukemia in Remission
  • Childhood Chronic Myelogenous Leukemia
  • Childhood Myelodysplastic Syndromes
  • Chronic Phase Chronic Myelogenous Leukemia
  • de Novo Myelodysplastic Syndromes
  • Hematopoietic/Lymphoid Cancer
  • Leukemia
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Leukemia, Myeloid
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid, Chronic-Phase
  • Myelodysplastic Syndromes
  • Myelodysplastic-Myeloproliferative Diseases
  • Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
  • Myeloproliferative Disorders
  • Preleukemia
  • Previously Treated Myelodysplastic Syndromes
  • Recurrent Adult Acute Myeloid Leukemia
  • Recurrent Childhood Acute Myeloid Leukemia
  • Relapsing Chronic Myelogenous Leukemia
  • Syndrome

Intervention

Drug:
fludarabine phosphate
Given IV
busulfan
Given IV
Biological:
anti-thymocyte globulin
Given IV
Drug:
tacrolimus
Given IV and orally
methotrexate
Given IV
Procedure:
peripheral blood stem cell transplantation
Undergo allogeneic PBSC transplant
allogeneic hematopoietic stem cell transplantation
Undergo allogeneic PBSC transplant
Other:
laboratory biomarker analysis
Correlative studies

Locations

Country Name City State
United States Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Seattle Washington

Sponsors (3)

Lead Sponsor Collaborator
Fred Hutchinson Cancer Research Center National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Incidence of acute GvHD Maximum grade of acute GVHD and the number of therapies required to treat GVHD will be determined. Day 100 post-transplant No
Secondary Pharmacokinetics of IV busulfan including interdose variability and evaluation of a limited sampling strategy At 3.25, 4.5, 6, 8, 11, and 24-hours after the beginning of infusion on days -5, -4, and -3 No
Secondary Thymoglobulin pharmacokinetics On day -3 prior to the first dose, on day -1 one hour after completion of infusion and on day 1 at 0900 No
Secondary Incidence of donor cell engraftment By day 100 No
Secondary Incidence of system toxicities >= grade 3 as graded per CTCAE v.3 Up to day 100 after transplantation Yes
Secondary Incidence of chronic GvHD Day 100 No
Secondary Incidence of non-relapse mortality defined as death without history of post-transplant relapse At day 100 No
Secondary Incidence of non-relapse mortality defined as death without history of post-transplant relapse At 1 year No
Secondary 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. At 1 year No
Secondary Relapse-free survival At 1 year No
Secondary Incidence of EBV activation defined as an increase in plasma EBV DNA to >= 1000 copies/mL as determined by quantitative polymerase chain reaction (PCR) Up to 1 year No
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