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

NCT ID: NCT00392782

Last Updated: 2017-12-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-07-31
• Study Completion Date: 2011-05-31

Brief 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. 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.

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.

Conditions

Leukemia; Myelodysplastic Syndromes

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Natural Killer Cell Kir Epitope

Group Type: EXPERIMENTAL

anti-thymocyte globulin

Intervention Type: BIOLOGICAL

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 phosphate

Intervention Type: DRUG

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).

thiotepa

Intervention Type: DRUG

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

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

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 irradiation

Intervention Type: RADIATION

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.

Interventions

anti-thymocyte globulin

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.

Intervention Type: BIOLOGICAL

fludarabine phosphate

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).

Intervention Type: DRUG

thiotepa

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

Intervention Type: DRUG

peripheral blood stem cell transplantation

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.

Intervention Type: PROCEDURE

total-body irradiation

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.

Intervention Type: RADIATION

Other Intervention Names

ATG; Fludara; PBSC; TBI

Eligibility Criteria

Inclusion Criteria

• 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

• 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

Exclusion Criteria

• 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.
• 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

• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Center for International Blood and Marrow Transplant Research

NETWORK

Sponsor Role: collaborator

Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Daniel J. Weisdorf, MD

Role: PRINCIPAL_INVESTIGATOR

Masonic Cancer Center, University of Minnesota

Locations

Moffitt Cancer Center

Tampa, Florida, United States

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, United States

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, United States

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

Columbus, Ohio, United States

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Medical College of Wisconsin Cancer Center

Milwaukee, Wisconsin, United States

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

Milwaukee, Wisconsin, United States

Countries

United States

Other Identifiers

UMN-MT2004-04

Identifier Type: OTHER

Identifier Source: secondary_id

UMN-0405M59662

Identifier Type: OTHER

Identifier Source: secondary_id

2004UC035

Identifier Type: -

Identifier Source: org_study_id