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

NCT00392782 | Terminated Phase 2 Results DMC

• 3 other identifiers: 2004UC035UMN-MT2004-04UMN-0405M59662
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 9

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.

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

Outcome Measures

Primary Outcomes (1)

• Incidence of Disease-free Survival

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

  1 Year

Secondary Outcomes (6)

• Incidence of Disease Relapse

  1 Year

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

  Day 100

• Incidence of Chronic Graft-versus-host Disease (GVHD)

  1 Year

• Incidence of Graft Failure

  Day 100

• Transplant-related Mortality

  1 Year

Study Arms (1)

Natural Killer Cell Kir Epitope

EXPERIMENTAL

Biological: anti-thymocyte globulin; Drug: fludarabine phosphate; Drug: thiotepa; Procedure: peripheral blood stem cell transplantation; Radiation: total-body irradiation

Interventions

anti-thymocyte globulin 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.

Also known as: ATG

Natural Killer Cell Kir Epitope

fludarabine phosphate 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).

Also known as: Fludara

Natural Killer Cell Kir Epitope

thiotepa DRUG

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

Natural Killer Cell Kir Epitope

peripheral blood stem cell transplantation 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.

Also known as: PBSC

Natural Killer Cell Kir Epitope

total-body irradiation 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.

Also known as: TBI

Natural Killer Cell Kir Epitope

Eligibility Criteria

• Age: Up to 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead
• Center for International Blood and Marrow Transplant Research: collaborator

Study Sites (9)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202-5289, United States

Location

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, 63110, United States

Location

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

Columbus, Ohio, 43210-1240, United States

Location

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104-4283, United States

Location

Medical College of Wisconsin Cancer Center

Milwaukee, Wisconsin, 53226, United States

Location

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

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes; Congenital Abnormalities; Leukemia, Myeloid, Acute; Leukemia, Myeloid, Accelerated Phase; Blast Crisis

Interventions

Antilymphocyte Serum; fludarabine phosphate; Thiotepa; Peripheral Blood Stem Cell Transplantation; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myeloproliferative Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Phosphoramides; Organophosphorus Compounds; Organic Chemicals; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Radiotherapy; Investigative Techniques

Results Point of Contact

• Title: Daniel Weisdorf, M.D.
• Organization: Masonic Cancer Center, University of Minnesota

weisd001@umn.edu

612-624-0123

Study Officials

• Daniel J. Weisdorf, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2006
• First Posted: October 26, 2006
• Study Start: July 1, 2005
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: December 28, 2017
• Results First Posted: July 15, 2011

Record last verified: 2017-12

Locations

US (9)