Graft Versus Host DiseasePhase 2NCT00611351
Busulfan, Cyclophosphamide, & Antithymocyte Globulin Followed by Stem Cell Transplant in Treating Hematologic Cancer
A Phase 2 study testing anti-thymocyte globulin, busulfan and cyclophosphamide in people with Graft Versus Host Disease and Leukemia, run by University of Nebraska at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 19 to 65 years
- Conditions the study is for
- Graft Versus Host Disease, Leukemia, Lymphoma
- What is being tested?
- anti-thymocyte globulin, busulfan and cyclophosphamide
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Jun 2005to 17 Sep 2008
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 21Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Unversity of Nebraska Medical Center
Omaha, Nebraska, 68198
About this study
Official title: 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.
Read the 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.
- Conditions
- Graft Versus Host Disease, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases
- Being tested
- anti-thymocyte globulin, busulfan, cyclophosphamide, mycophenolate mofetil, tacrolimus
- Keywords
- graft versus host disease, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, 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, untreated adult acute myeloid leukemia, untreated adult acute lymphoblastic leukemia, accelerated phase chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia, relapsing chronic myelogenous leukemia, stage III multiple myeloma, refractory multiple myeloma, de novo myelodysplastic syndromes, myelodysplastic/myeloproliferative disease, unclassifiable, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, secondary myelofibrosis
- Medical subject headings
- Graft vs Host Disease, Leukemia, Lymphoma, Multiple Myeloma, Neoplasms, Plasma Cell, Myelodysplastic Syndromes, Myelodysplastic-Myeloproliferative Diseases, Congenital Abnormalities
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anti-thymocyte globulinBiological
Also called immunosuppressant
busulfanDrug
Also called Busulfex, Myleran
cyclophosphamideDrug
Also called cytophosphane
Also called CellCept
tacrolimusDrug
Also called Protopic, Envarsus XR, Astagraf XL
polymerase chain reactionGenetic
polymorphism analysisGenetic
flow cytometryOther
laboratory biomarker analysisOther
pharmacogenomic studiesOther
allogeneic bone marrow transplantationProcedure or surgery
allogeneic hematopoietic stem cell transplantationProcedure or surgery
peripheral blood stem cell transplantationProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| Unrelated Donor Allogeneic | Experimental | Matched unrelated donor allogeneic stem cell transplantation with a conditioning regimen of targeted busulfan, cyclophosphamide and thymoglobulin. Receives: Biological: anti-thymocyte globulin; Drug: busulfan; Drug: cyclophosphamide; Drug: mycophenolate mofetil; Drug: tacrolimus; Genetic: polymerase chain reaction; Genetic: polymorphism analysis; Other: flow cytometry; Other: laboratory biomarker analysis; Other: pharmacogenomic studies; Other: pharmacological study; Procedure: allogeneic bone marrow transplantation; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Transplantation-related Mortality at 100 Days Post-transplantation
Measured: at the 100 days post-transplant
Secondary outcomes (3)
Incidence of Grade II-IV Acute Graft-versus-host-disease (GVHD)
Measured: at day 100 post transplantation
Overall Survival
Measured: 2 years post transplant
Event-free Survival
Measured: 2 years post transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2008 (estimated)
- Study start7 Jun 2005
- Primary completion1 Feb 2008
- Study completion17 Sep 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Graft Versus Host DiseaseStudies of the same condition, open and under way.
- More trials run by University of NebraskaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Nebraska
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Marcel Devetten, MD, Principal investigator, University of Nebraska
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00611351
- Sponsor's protocol ID
- 0122-05-FB
- Other IDs
- P30CA036727
- Status last verified
- Oct 2023
- First submitted
- 7 Feb 2008
- Last updated
- 23 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Matched Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplantation With a Conditioning Regimen of Targeted Busulfan, Cyclophosphamide, and Thymoglobulin
- ClinicalTrials.gov ID
- NCT00611351
- Acronym / sponsor ID
- 0122-05-FB
- Conditions
- Graft Versus Host Disease, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases
- Keywords
- graft versus host disease, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, 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, untreated adult acute myeloid leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- University of NebraskaUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 7 Jun 2005 (actual)
- Primary completion
- 1 Feb 2008 (actual)
- Study completion
- 17 Sep 2008 (actual)
- First posted
- 8 Feb 2008 (estimated)
- Results
- Posted 3 Apr 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Unrelated Donor Allogeneic | Experimental | Biological: anti-thymocyte globulin, Drug: busulfan, Drug: cyclophosphamide, Drug: mycophenolate mofetil, Drug: tacrolimus, Genetic: polymerase chain reaction, Genetic: polymorphism analysis, Other: flow cytometry, Other: laboratory biomarker analysis, Other: pharmacogenomic studies, Other: pharmacological study, Procedure: allogeneic bone marrow transplantation, Procedure: allogeneic hematopoietic stem cell transplantation, Procedure: peripheral blood stem cell transplantationMatched unrelated donor allogeneic stem cell transplantation with a conditioning regimen of targeted busulfan, cyclophosphamide and thymoglobulin. |
Who may qualify
- Ages
- 19 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Pathologically confirmed diagnosis of 1 of the following:
- Requirement for myeloablative conditioning regimen confirmed by attending physician
- Available donor must meet the following criteria:
- Karnofsky performance status 70-100%
- DLCO ≥ 50% predicted
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| anti-thymocyte globulinAlso: immunosuppressant | Biological | Unrelated Donor Allogeneic |
| busulfanAlso: Busulfex, Myleran | Drug | Unrelated Donor Allogeneic |
| cyclophosphamideAlso: cytophosphane | Drug | Unrelated Donor Allogeneic |
| mycophenolate mofetilAlso: CellCept | Drug | Unrelated Donor Allogeneic |
| tacrolimusAlso: Protopic, Envarsus XR, Astagraf XL | Drug | Unrelated Donor Allogeneic |
| polymerase chain reaction | Genetic | Unrelated Donor Allogeneic |
| polymorphism analysis | Genetic | Unrelated Donor Allogeneic |
| flow cytometry | Other | Unrelated Donor Allogeneic |
| laboratory biomarker analysis | Other | Unrelated Donor Allogeneic |
| pharmacogenomic studies | Other | Unrelated Donor Allogeneic |
| pharmacological study | Other | Unrelated Donor Allogeneic |
| allogeneic bone marrow transplantation | Procedure or surgery | Unrelated Donor Allogeneic |
| allogeneic hematopoietic stem cell transplantation | Procedure or surgery | Unrelated Donor Allogeneic |
| peripheral blood stem cell transplantation | Procedure or surgery | Unrelated Donor Allogeneic |
Primary outcome
Transplantation-related Mortality at 100 Days Post-transplantation
Time frame: at the 100 days post-transplant
3 secondary outcomes
Incidence of Grade II-IV Acute Graft-versus-host-disease (GVHD)
Time frame: at day 100 post transplantation
Overall Survival
Time frame: 2 years post transplant
Event-free Survival
Time frame: 2 years post transplant
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marcel Devetten, MD principal investigator
University of Nebraska
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing anti-thymocyte globulin, busulfan and cyclophosphamide in people with Graft Versus Host Disease and Leukemia, run by University of Nebraska at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Apr 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Transplantation-related Mortality at 100 Days Post-transplantation (time frame: at the 100 days post-transplant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2023.