Donor Peripheral Stem Cell Transplant and Donor Natural Killer Cell Transplant After Total-Body Irradiation, Thiotepa, Fludarabine, and Muromonab-CD3 in Treating Patients With Leukemia or Other Blood Diseases

NCT00450983 | Terminated Phase 2 Results

• 5 other identifiers: 1965.00R01AI053193P30CA015704FHCRC-1965.00CDR0000533834
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 2

Brief Summary

RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell and donor natural killer cell transplant helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When certain 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. Removing the T cells from the donor cells before transplant may stop this from happening. PURPOSE: This phase II trial is studying how well giving a donor peripheral stem cell transplant and a donor natural killer cell transplant after total-body irradiation, thiotepa, fludarabine, and muromonab-CD3 works in treating patients with leukemia or other blood diseases.

Conditions

Graft Versus Host Disease; Leukemia; Myelodysplastic Syndromes

Keywords

graft versus host disease; adult acute lymphoblastic leukemia in remission; recurrent adult acute lymphoblastic leukemia; childhood acute lymphoblastic leukemia in remission; recurrent childhood acute lymphoblastic leukemia; adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia in remission; recurrent adult acute myeloid leukemia; childhood acute myeloid leukemia in remission; recurrent childhood acute myeloid leukemia; secondary acute myeloid leukemia; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; accelerated phase chronic myelogenous leukemia; blastic phase chronic myelogenous leukemia; childhood chronic myelogenous leukemia; relapsing chronic myelogenous leukemia; 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); childhood myelodysplastic syndromes

Outcome Measures

Primary Outcomes (1)

• Risk of Developing Grades III-IV Acute Graft-vs-host Disease (GVHD)

  Count of participants with acute GVHD grades III-IV.

  Up to day 100

Secondary Outcomes (8)

• Risk for Mortality From Infection Before Day 180

  Up to day 180

• Risk for Graft Failure

  Engraftment documented day +20

• Risk for Life-threatening Infections

  Up to day 100

• Concentration of NK, NK-T, T-cells, and Dendritic Cell Subsets in the CD34+ NK/NK-T-enriched Graft

  Up to 5 years

• Cytomegalovirus-specific T Cells in Product and Donor Graft

  Up to 5 years

Interventions

muromonab-CD3 BIOLOGICAL

natural killer cell therapy BIOLOGICAL

fludarabine phosphate DRUG

methotrexate DRUG

thiotepa DRUG

gene expression analysis GENETIC

flow cytometry OTHER

immunologic technique OTHER

allogeneic hematopoietic stem cell transplantation PROCEDURE

in vitro-treated peripheral blood stem cell transplantation PROCEDURE

total-body irradiation RADIATION

Eligibility Criteria

• Age: Up to 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

DISEASE CHARACTERISTICS: * Diagnosis of 1 of the following life-threatening hematological malignancies: * Acute lymphoblastic leukemia meeting 1 of the following criteria: * Advanced beyond first remission * In first remission with high-risk prognostic features, including any of the following: * Philadelphia chromosome-positive disease * Chromosome 11q23 abnormality * Hypodiploid * Failed to achieve first remission within 1 month after induction * Acute myeloid leukemia (AML) meeting 1 of the following criteria: * Advanced beyond first remission * First remission with high-risk prognostic features, including any of the following: * Chromosome 11q23 abnormality * Chromosome del 7q * Secondary AML * Failed to achieve first remission within 1 month after induction * Myelodysplastic syndromes with International Prognostic Score \> 1 * Chronic myelogenous leukemia in accelerated or blastic phase * No active CNS disease * No suitable HLA-matched related or unrelated donor available * Haploidentical family member available as donor of partially HLA-matched peripheral blood stem cells * Least degree of mismatch to HLA-A, B, C, DRB1, and DQB1 * No mismatch for a single HLA-A, B, C, DRB1, or DQB1 antigen * Donor killer cell immunoglobulin-like receptor ligand group expression preferably different than patient PATIENT CHARACTERISTICS: * LVEF ≥ 45% * DLCO ≥ 60% of predicted * AST and ALT ≤ 2 times upper limit of normal (ULN) (unless due to malignancy) * Bilirubin ≤ 2 times ULN (unless due to malignancy) * No life expectancy \< 6 months due to coexisting disease other than the malignancy * No active infection (e.g., polymerase chain reaction \[PCR\] evidence for cytomegalovirus, human herpes virus 6, or invasive fungal infection) * No prior infections without evidence of resolution by PCR or imaging studies within the past 2 months * No hypersensitivity to murine antibodies * No known HIV positivity * Not pregnant or nursing * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: * No prior marrow transplantation with total body irradiation \> 400 cGy * No concurrent therapies for seizure disorder * No growth factors for 21 days after transplantation

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (2)

Seattle Cancer Care Alliance

Seattle, Washington, 98109-1023, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109-1024, United States

Location

MeSH Terms

Conditions

Graft vs Host Disease; Leukemia; Myelodysplastic Syndromes; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Congenital Abnormalities; Leukemia, Myeloid, Acute; Leukemia, Myeloid, Accelerated Phase; Blast Crisis

Interventions

Muromonab-CD3; fludarabine phosphate; Methotrexate; Thiotepa; Gene Expression Profiling; Flow Cytometry; Immunologic Techniques; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; 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)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Immunoglobulin G; Immunoglobulin Isotypes; Serum Globulins; Globulins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phosphoramides; Organophosphorus Compounds; Organic Chemicals; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Genetic Techniques; Investigative Techniques; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry; Chemistry Techniques, Analytical; Radiotherapy; Therapeutics

Results Point of Contact

• Title: Ann Woolfrey, MD
• Organization: Fred Hutchinson Cancer Research Center

awoolfre@fredhutch.org

206-667-4453

Study Officials

• Ann Woolfrey, MD

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 20, 2007
• First Posted: March 22, 2007
• Study Start: December 1, 2006
• Primary Completion: July 1, 2010
• Study Completion: July 1, 2010
• Last Updated: May 24, 2017
• Results First Posted: May 24, 2017

Record last verified: 2017-04

Locations

US (2)