Busulfan, Cyclophosphamide, & Antithymocyte Globulin Followed by Stem Cell Transplant in Treating Hematologic Cancer

October 5, 2023 updated by: University of Nebraska

Matched Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplantation With a Conditioning Regimen of Targeted Busulfan, Cyclophosphamide, and Thymoglobulin

RATIONALE: Giving chemotherapy before a donor bone marrow transplant or peripheral stem cell transplant helps stop the growth of cancer 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. Giving tacrolimus and mycophenolate mofetil after the transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving busulfan together with cyclophosphamide and antithymocyte globulin followed by donor stem cell transplant works in treating patients with hematologic cancer.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • To determine the incidence of grade II-IV acute graft-versus-host disease in patients with hematologic cancer or other diseases treated with a myeloablative conditioning regimen comprising targeted (steady-state concentration of 800-1,000 ng/mL) busulfan, cyclophosphamide, and anti-thymocyte globulin followed by matched unrelated donor allogeneic hematopoietic stem cell transplantation.
  • To determine the day +100 transplantation-related mortality in these patients.

Secondary

  • To determine the effect of cyclophosphamide pharmacokinetic parameters on day +100 transplantation-related mortality in these patients.
  • To determine the ability of low-dose anti-thymocyte globulin administered on day +5 to induce activation-induced cell death of activated donor lymphocytes.
  • To determine the incidence of chronic graft-versus-host disease in patients treated with this regimen.
  • To determine event-free and overall survival of patients treated with this regimen.
  • To evaluate pharmacogenomic associations between genetic polymorphisms in drug disposition enzymes with the pharmacokinetics of busulfan and cyclophosphamide.

OUTLINE:

  • Myeloablative conditioning regimen: Patients receive busulfan IV over 2 hours on days -8 to -5; cyclophosphamide IV over 4 hours on days -3 to -2; and anti-thymocyte globulin IV over 6 hours on day -3 and then over 4 hours on days -2, -1, and 5.
  • Allogeneic hematopoietic stem cell transplantation: Patients undergo allogeneic bone marrow or peripheral blood stem cell infusion on day 0.
  • Graft-versus-host-disease prophylaxis: Patients receive tacrolimus IV continuously or orally on days 6 to150, followed by an even taper to day 180 in the absence of graft-versus-host-disease. Patients also receive mycophenolate mofetil IV or orally beginning on day 6 and continuing to day 28.

Patients undergo blood collection periodically during study for pharmacokinetic, pharmacogenomic, and other translational studies. Genomic DNA extracted from blood samples is analyzed by polymerase chain reaction for genetic polymorphisms in cyclophosphamide/busulfan disposition enzymes. Activated donor lymphocytes are assessed using flow cytometry to measure activation-induced cell death, as reflected by apoptosis in activated T cells. Chimerism on or around day 100 is also assessed using fluorescence in situ hybridization analysis and DNA fingerprinting.

After completion of study treatment, patients are followed periodically.

Study Type

Interventional

Enrollment (Actual)

5

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • Unversity of Nebraska Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

17 years to 63 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Pathologically confirmed diagnosis of 1 of the following:

    • Acute myeloid leukemia
    • Acute lymphocytic leukemia
    • Chronic myelogenous leukemia beyond first chronic phase (i.e., 2nd chronic phase, accelerated phase, or blast crisis)
    • Multiple myeloma
    • Myelodysplastic syndromes
    • Malignant lymphoma
    • Myelofibrosis
  • Requirement for myeloablative conditioning regimen confirmed by attending physician

  • Available donor must meet the following criteria:

    • HLA phenotypically identical unrelated donor by low, intermediate, or high resolution for HLA class I antigens, and by high resolution for HLA class II antigens
    • Matched at the A, B, and DRβ1 loci
    • Single HLA-A or HLA-B antigen mismatch allowed
    • Meets all National Marrow Donor Program or foreign registry criteria for allogeneic bone marrow/stem cell donors
    • Peripheral blood stem cells are the preferred product on this study but bone marrow is allowed
  • Karnofsky performance status 70-100%
  • DLCO ≥ 50% predicted
  • LVEF ≥ 45%
  • Serum creatinine ≤ 1.5 mg/dL or creatinine clearance ≥ 65 mL/min
  • Serum total bilirubin ≤ 2.0 mg/dL
  • Fertile patients must use effective contraception

Exclusion Criteria:

  • No active uncontrolled infection
  • Not pregnant or nursing/negative pregnancy test
  • No HIV infection
  • No chronic active hepatitis B or C or evidence of cirrhosis on liver biopsy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Unrelated Donor Allogeneic
Matched unrelated donor allogeneic stem cell transplantation with a conditioning regimen of targeted busulfan, cyclophosphamide and thymoglobulin.
Drug: cyclophosphamide
Other Names:
  • cytophosphane
Genetic: polymorphism analysis
Other: pharmacological study
Other: laboratory biomarker analysis
Other: pharmacogenomic studies
Biological: anti-thymocyte globulin
Other Names:
  • immunosuppressant
Procedure: allogeneic bone marrow transplantation
Procedure: allogeneic hematopoietic stem cell transplantation
Drug: busulfan
Other Names:
  • Busulfex, Myleran
Procedure: peripheral blood stem cell transplantation
Other: flow cytometry
Genetic: polymerase chain reaction
Drug: tacrolimus
Other Names:
  • Protopic, Envarsus XR, Astagraf XL
Drug: mycophenolate mofetil
Other Names:
  • CellCept

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Transplantation-related Mortality at 100 Days Post-transplantation
Time Frame: at the 100 days post-transplant
at the 100 days post-transplant

Secondary Outcome Measures

Outcome Measure
Time Frame
Incidence of Grade II-IV Acute Graft-versus-host-disease (GVHD)
Time Frame: at day 100 post transplantation
at day 100 post transplantation
Overall Survival
Time Frame: 2 years post transplant
2 years post transplant
Event-free Survival
Time Frame: 2 years post transplant
2 years post transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Nebraska

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Marcel Devetten, MD, University of Nebraska

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 7, 2005

Primary Completion (Actual)

February 1, 2008

Study Completion (Actual)

September 17, 2008

Study Registration Dates

First Submitted

February 7, 2008

First Submitted That Met QC Criteria

February 7, 2008

First Posted (Estimated)

February 8, 2008

Study Record Updates

Last Update Posted (Actual)

October 23, 2023

Last Update Submitted That Met QC Criteria

October 5, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0122-05-FB
  • P30CA036727 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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