Adult Acute Myeloid Leukemia in RemissionNCT00445744
Cyclophosphamide and Busulfan Followed by Donor Stem Cell Transplant in Treating Patients With Myelofibrosis, Acute Myeloid Leukemia, or Myelodysplastic Syndrome
A study testing cyclophosphamide, busulfan and tacrolimus in people with Adult Acute Myeloid Leukemia in Remission and Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, run by Fred Hutchinson Cancer Center at 1 site in United States.
Trial summary
This trial is studying the side effects and how well giving cyclophosphamide and busulfan followed by donor stem cell transplant works in treating patients with myelofibrosis, acute myeloid leukemia, or myelodysplastic syndrome. Read more about this study
- Who is it for?
- Ages Up to 65 years
- Conditions the study is for
- Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q)
- What is being tested?
- cyclophosphamide, busulfan and tacrolimus
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2006to Jun 2013
- Phase
- Interventional
- 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 Up to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Idiopathic myelofibrosis (CIMF)
- Myelofibrosis developing with polycythemia vera or essential thrombocythemia
- Acute myeloid leukemia with or without antecedent hematologic disorder, at any disease stage (complete remission, minimal residual disease, or relapsed leukemia)
- Myelodysplastic syndrome of any World Health Organization (WHO) or French-American-British (FAB) category, at any disease stage
- Less than 61 years of age if transplanted from an unrelated donor, or less than 66 years of age if transplanted from a related donor
- Receiving unmanipulated peripheral blood stem cells from an human leukocyte antigen (HLA)-identical or 1-allele-mismatched related or unrelated donor, or receiving G-CSF-stimulated bone marrow if co-enrolled on Fred Hutchinson Cancer Research Center (FHCRC) protocol 2250
Show all 12Show fewer
- With a Karnofsky Performance score of > 70% at the time of pre-transplant evaluation
- Able to give informed consent (if >= 18 years of age), or with a legal guardian capable of giving consent (if < 18 years of age)
- DONOR: HLA-identical or 1-allele-mismatched related or unrelated donors (by high resolution typing)
- DONOR: Undergoing peripheral blood stem cell harvest or G-CSF-stimulated bone marrow harvest (bone marrow permitted only as part of FHCRC protocol 2250)
- DONOR: In good general health, with a Karnofsky performance score of > 80%
- DONOR: Able to give informed consent (if >= 18 years of age), or with a legal guardian able to give informed consent (if < 18 years of age and donating for a related transplant)
Who cannot join
- Without an HLA-identical or 1-allele-mismatched related or unrelated donor
- With human immunodeficiency virus (HIV) positivity or active infectious hepatitis
- Receiving a medication known to strongly inhibit enzymes in the CYP450 pathway, and which, in the judgment of the consenting provider, cannot be safely discontinued for the duration of conditioning
- Whose life expectancy is severely limited by diseases other than the hematologic disorder for which they are undergoing HCT (HCT-comorbidity index [CI] > 3)
- Women who are pregnant or lactating
- With known hypersensitivity to BU or CY
Show all 15Show fewer
- With hepatic dysfunction as evidenced by total bilirubin or AST > 2x the upper limit of normal, or evidence of synthetic dysfunction or cirrhosis
- With impaired renal function, as evidenced by creatinine clearance < 50% of expected, creatinine > 2x the upper limit of normal, or dialysis dependence
- With impaired pulmonary function, as evidenced by pO2 < 70 mm Hg and diffusing capacity of carbon monoxide (DLCO) < 70% predicted or by pO2 < 80 mm Hg and DLCO < 60%, or receiving continuous supplementary oxygen
- With impaired cardiac function, as evidenced by ejection fraction < 35% or active coronary artery disease
- Unable to give informed consent
- DONOR: Deemed unable to undergo stem cell collection, for any reason
- DONOR: HIV-positive, or hepatitis B or C antigen-positive
- DONOR: Women with a positive pregnancy test
- DONOR: Unable to give informed consent (if >= 18 years of age), or without a legal guardian able to give informed consent (if <18 years of age)
Trial locations and contacts
1 site in 1 country.
United States1 site
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, 98109
About this study
Official title: Cyclophosphamide Followed by Intravenous Busulfan as Conditioning for Hematopoietic Cell Transplantation in Patients With Myelofibrosis, Acute Myeloid Leukemia, or Myelodysplastic Syndrome.
This trial is studying the side effects and how well giving cyclophosphamide and busulfan followed by donor stem cell transplant works in treating patients with myelofibrosis, acute myeloid leukemia, or myelodysplastic syndrome. Giving chemotherapy, such as cyclophosphamide and busulfan, before a donor stem cell transplant helps stops the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus and methotrexate after the transplant may stop this from happening
Read the detailed description
PRIMARY OBJECTIVES:
- To estimate the incidence of hepatotoxicity with a conditioning regimen of CY (cyclophosphamide)/tBU (busulfan) in patients receiving hematopoietic cell transplant (HCT).
SECONDARY OBJECTIVES:
- To determine overall and non-relapse mortality at day +200 after HCT.
II. To determine the peak bilirubin levels through day +20 after HCT.
III. To determine the incidence of pulmonary toxicity in the form of idiopathic pulmonary syndrome (IPS).
IV. To determine the rate of graft failure.
- To determine the time to engraftment.
VI. To determine the rate of relapse.
VII. To determine the incidence and severity of graft-versus-host disease (GVHD).
VIII. To evaluate the pharmacokinetics/dynamics of BU and CY.
- To evaluate the pharmacogenomics of response, toxicity and pharmacokinetics of CY/tBU.
OUTLINE:
CONDITIONING REGIMEN: Patients receive cyclophosphamide intravenously (IV) on days -7 and -6 and busulfan IV over 3 hours on days -5 to -2.
TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplant on day 0.
POST-TRANSPLANT IMMUNOSUPPRESSION: Patients receive tacrolimus IV or orally (PO) twice daily on days -1 to 200 with taper on day 56 and methotrexate on days 1, 3, 6, and 11.
After completion of study treatment, patients are followed periodically.
- Conditions
- Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), 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)
- Being tested
- cyclophosphamide, busulfan, tacrolimus, methotrexate, cytogenetic analysis
- Medical subject headings
- Congenital Abnormalities, Thrombocythemia, Essential, Chromosome 5q Deletion Syndrome, Polycythemia Vera, Primary Myelofibrosis, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cyclophosphamideDrug
Also called CPM, CTX, Cytoxan, Endoxan
Given IV
busulfanDrug
Also called BSF, BU, Misulfan, Mitosan
Given IV
tacrolimusDrug
Also called FK 506, Prograf
Given IV or PO
methotrexateDrug
Also called amethopterin, Folex, methylaminopterin, Mexate
Given IV
cytogenetic analysisGenetic
Correlative studies
flow cytometryOther
Correlative studies
Also called pharmacological studies
Correlative studies
pharmacogenomic studiesOther
Also called Pharmacogenomic Study
Correlative studies
peripheral blood stem cell transplantationProcedure or surgery
Also called PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell
Undergo PBPC transplantation
allogeneic hematopoietic stem cell transplantationProcedure or surgery
Undergo allogeneic transplantation
| Study group | Role | What they receive |
|---|---|---|
| Treatment (cyclophosphamide, busulfan, transplant) | Experimental | CONDITIONING REGIMEN: Patients receive cyclophosphamide IV on days -7 and -6 and busulfan IV over 3 hours on days -5 to -2.
TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplant on day 0.
POST-TRANSPLANT IMMUNOSUPPRESSION: Patients receive tacrolimus IV or PO twice daily on days -1 to 200 with taper on day 56 and methotrexate on days 1, 3, 6, and 11. Receives: Drug: cyclophosphamide; Drug: busulfan; Drug: tacrolimus; Drug: methotrexate; Genetic: cytogenetic analysis; Other: flow cytometry; Other: pharmacological study; Other: pharmacogenomic studies; Procedure: peripheral blood stem cell transplantation; Procedure: allogeneic hematopoietic stem cell transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effectiveness of Cyclophosphamide/Busulfan Regimen in Reducing Regimen-related Liver Toxicity
Number of patients with regimen-related liver toxicity. Diagnoses will be made according to the established criteria initially proposed in 1984 by McDonald et al.
Measured: Up to day +20
Non-relapse Mortality (NRM) (Patients With AML/MDS)
Cumulative incidence rate with death as a competing risk, assessed at day 100.
Measured: Up to day 200
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2007 (estimated)
- Study startDec 2006
- Primary completionJun 2011
- Study completionJun 2013
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 Adult Acute Myeloid Leukemia in RemissionStudies of the same condition, open and under way.
- More trials run by Fred Hutchinson Cancer CenterThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fred Hutchinson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Joachim Deeg, Fred Hutchinson Cancer Center
- Investigators
- Andrew Rezvani, Principal investigator, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00445744
- Sponsor's protocol ID
- 2130.00
- Other IDs
- NCI-2010-00270, P01HL036444
- Status last verified
- Dec 2017
- First submitted
- 7 Mar 2007
- Last updated
- 2 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cyclophosphamide Followed by Intravenous Busulfan as Conditioning for Hematopoietic Cell Transplantation in Patients With Myelofibrosis, Acute Myeloid Leukemia, or Myelodysplastic Syndrome.
- ClinicalTrials.gov ID
- NCT00445744
- Acronym / sponsor ID
- 2130.00
- Conditions
- Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), 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)
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Fred Hutchinson Cancer CenterUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), National Cancer Institute (NCI)
- Study start
- Dec 2006
- Primary completion
- Jun 2011 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 9 Mar 2007 (estimated)
- Results
- Posted 2 Jan 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial is studying the side effects and how well giving cyclophosphamide and busulfan followed by donor stem cell transplant works in treating patients with myelofibrosis, acute myeloid leukemia, or myelodysplastic syndrome. Giving chemotherapy, such as cyclophosphamide and busulfan, before a donor stem cell transplant helps stops the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus and methotrexate after the transplant may stop this from happening
Detailed description
PRIMARY OBJECTIVES:
- To estimate the incidence of hepatotoxicity with a conditioning regimen of CY (cyclophosphamide)/tBU (busulfan) in patients receiving hematopoietic cell transplant (HCT).
SECONDARY OBJECTIVES:
- To determine overall and non-relapse mortality at day +200 after HCT.
II. To determine the peak bilirubin levels through day +20 after HCT.
III. To determine the incidence of pulmonary toxicity in the form of idiopathic pulmonary syndrome (IPS).
IV. To determine the rate of graft failure.
- To determine the time to engraftment.
VI. To determine the rate of relapse.
VII. To determine the incidence and severity of graft-versus-host disease (GVHD).
VIII. To evaluate the pharmacokinetics/dynamics of BU and CY.
- To evaluate the pharmacogenomics of response, toxicity and pharmacokinetics of CY/tBU.
OUTLINE:
CONDITIONING REGIMEN: Patients receive cyclophosphamide intravenously (IV) on days -7 and -6 and busulfan IV over 3 hours on days -5 to -2.
TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplant on day 0.
POST-TRANSPLANT IMMUNOSUPPRESSION: Patients receive tacrolimus IV or orally (PO) twice daily on days -1 to 200 with taper on day 56 and methotrexate on days 1, 3, 6, and 11.
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 |
|---|---|---|
| Treatment (cyclophosphamide, busulfan, transplant) | Experimental | Drug: cyclophosphamide, Drug: busulfan, Drug: tacrolimus, Drug: methotrexate, Genetic: cytogenetic analysis, Other: flow cytometry, Other: pharmacological study, Other: pharmacogenomic studies, Procedure: peripheral blood stem cell transplantation, Procedure: allogeneic hematopoietic stem cell transplantationCONDITIONING REGIMEN: Patients receive cyclophosphamide IV on days -7 and -6 and busulfan IV over 3 hours on days -5 to -2. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplant on day 0. POST-TRANSPLANT IMMUNOSUPPRESSION: Patients receive tacrolimus IV or PO twice daily on days -1 to 200 with taper on day 56 and methotrexate on days 1, 3, 6, and 11. |
Who may qualify
- Ages
- Up to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (12 listed)
- Idiopathic myelofibrosis (CIMF)
- Myelofibrosis developing with polycythemia vera or essential thrombocythemia
- Acute myeloid leukemia with or without antecedent hematologic disorder, at any disease stage (complete remission, minimal residual disease, or relapsed leukemia)
- Myelodysplastic syndrome of any World Health Organization (WHO) or French-American-British (FAB) category, at any disease stage
- Less than 61 years of age if transplanted from an unrelated donor, or less than 66 years of age if transplanted from a related donor
Key exclusion criteria (15 listed)
- Without an HLA-identical or 1-allele-mismatched related or unrelated donor
- With human immunodeficiency virus (HIV) positivity or active infectious hepatitis
- Receiving a medication known to strongly inhibit enzymes in the CYP450 pathway, and which, in the judgment of the consenting provider, cannot be safely discontinued for the duration of conditioning
- Whose life expectancy is severely limited by diseases other than the hematologic disorder for which they are undergoing HCT (HCT-comorbidity index [CI] > 3)
- Women who are pregnant or lactating
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 |
|---|---|---|
| cyclophosphamideAlso: CPM, CTX, Cytoxan, EndoxanGiven IV | Drug | Treatment (cyclophosphamide, busulfan, transplant) |
| busulfanAlso: BSF, BU, Misulfan, MitosanGiven IV | Drug | Treatment (cyclophosphamide, busulfan, transplant) |
| tacrolimusAlso: FK 506, PrografGiven IV or PO | Drug | Treatment (cyclophosphamide, busulfan, transplant) |
| methotrexateAlso: amethopterin, Folex, methylaminopterin, MexateGiven IV | Drug | Treatment (cyclophosphamide, busulfan, transplant) |
| cytogenetic analysisCorrelative studies | Genetic | Treatment (cyclophosphamide, busulfan, transplant) |
| flow cytometryCorrelative studies | Other | Treatment (cyclophosphamide, busulfan, transplant) |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Treatment (cyclophosphamide, busulfan, transplant) |
| pharmacogenomic studiesAlso: Pharmacogenomic StudyCorrelative studies | Other | Treatment (cyclophosphamide, busulfan, transplant) |
| peripheral blood stem cell transplantationAlso: PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cellUndergo PBPC transplantation | Procedure or surgery | Treatment (cyclophosphamide, busulfan, transplant) |
| allogeneic hematopoietic stem cell transplantationUndergo allogeneic transplantation | Procedure or surgery | Treatment (cyclophosphamide, busulfan, transplant) |
Primary outcome
Effectiveness of Cyclophosphamide/Busulfan Regimen in Reducing Regimen-related Liver Toxicity
Time frame: Up to day +20
Number of patients with regimen-related liver toxicity. Diagnoses will be made according to the established criteria initially proposed in 1984 by McDonald et al.
Non-relapse Mortality (NRM) (Patients With AML/MDS)
Time frame: Up to day 200
Cumulative incidence rate with death as a competing risk, assessed at day 100.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jan 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Adult Acute Myeloid Leukemia in Remission
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingPhase 2
Personalized NK Cell Therapy in CBT
Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Acute Biphenotypic Leukemia
RecruitingObservational study
Tissue, Blood, and Body Fluid Sample Collection From Patients With Hematologic Cancer
Chronic Myeloproliferative Disorders, Leukemia
Active, not recruitingPhase 2
Azacitidine and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia
Acute Myeloid Leukemia, Adult Acute Megakaryoblastic Leukemia
Active, not recruitingObservational study
Infection Prophylaxis and Management in Treating Cytomegalovirus (CMV) Infection in Patients With Hematologic Malignancies Previously Treated With Donor Stem Cell Transplant
Hematopoietic/Lymphoid Cancer, Accelerated Phase Chronic Myelogenous Leukemia
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.
Andrew Rezvani principal investigator
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing cyclophosphamide, busulfan and tacrolimus in people with Adult Acute Myeloid Leukemia in Remission and Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, run by Fred Hutchinson Cancer Center 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 12 inclusion and 15 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 2 Jan 2018. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Jan 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?
Effectiveness of Cyclophosphamide/Busulfan Regimen in Reducing Regimen-related Liver Toxicity (time frame: Up to day +20). The study lists 2 primary outcomes in all. 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 2 Jan 2018.