Cyclophosphamide and Busulfan Followed by Donor Stem Cell Transplant in Treating Patients With Myelofibrosis, Acute Myeloid Leukemia, or Myelodysplastic Syndrome
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| ClinicalTrials.gov Identifier: NCT00445744 |
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Recruitment Status :
Completed
First Posted : March 9, 2007
Results First Posted : January 2, 2018
Last Update Posted : January 2, 2018
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Sponsor:
Fred Hutchinson Cancer Research Center
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Joachim Deeg, Fred Hutchinson Cancer Research Center
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Brief 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. 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
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| 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) Adult Acute Myeloid Leukemia With t(8;21)(q22;q22) Childhood Acute Myeloid Leukemia in Remission Childhood Myelodysplastic Syndromes de Novo Myelodysplastic Syndromes Essential Thrombocythemia Myelodysplastic Syndrome With Isolated Del(5q) Polycythemia Vera Previously Treated Myelodysplastic Syndromes Primary Myelofibrosis Recurrent Adult Acute Myeloid Leukemia Recurrent Childhood Acute Myeloid Leukemia Secondary Acute Myeloid Leukemia Secondary Myelodysplastic Syndromes Secondary Myelofibrosis Untreated Adult Acute Myeloid Leukemia Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies | 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 | Not Applicable |
PRIMARY OBJECTIVES:
I. To estimate the incidence of hepatotoxicity with a conditioning regimen of CY (cyclophosphamide)/tBU (busulfan) in patients receiving hematopoietic cell transplant (HCT).
SECONDARY OBJECTIVES:
I. 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.
V. 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.
X. 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 Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 52 participants |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Cyclophosphamide Followed by Intravenous Busulfan as Conditioning for Hematopoietic Cell Transplantation in Patients With Myelofibrosis, Acute Myeloid Leukemia, or Myelodysplastic Syndrome. |
| Study Start Date : | December 2006 |
| Actual Primary Completion Date : | June 2011 |
| Actual Study Completion Date : | June 2013 |
Resource links provided by the National Library of Medicine
Genetics Home Reference related topics:
Core binding factor acute myeloid leukemia
Cytogenetically normal acute myeloid leukemia
Familial acute myeloid leukemia with mutated CEBPA
Primary myelofibrosis
| Arm | Intervention/treatment |
|---|---|
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Experimental: Treatment (cyclophosphamide, busulfan, transplant)
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. |
Drug: cyclophosphamide
Given IV
Other Names:
Drug: busulfan Given IV
Other Names:
Drug: tacrolimus Given IV or PO
Other Names:
Drug: methotrexate Given IV
Other Names:
Genetic: cytogenetic analysis Correlative studies Other: flow cytometry Correlative studies Other: pharmacological study Correlative studies
Other Name: pharmacological studies Other: pharmacogenomic studies Correlative studies
Other Name: Pharmacogenomic Study Procedure: peripheral blood stem cell transplantation Undergo PBPC transplantation
Other Names:
Procedure: allogeneic hematopoietic stem cell transplantation Undergo allogeneic transplantation |
Primary Outcome Measures :
- 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.
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| Ages Eligible for Study: | up to 65 Years (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- 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
- 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)
Exclusion Criteria:
- 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
- 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)
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00445744
Locations
| United States, Washington | |
| Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | |
| Seattle, Washington, United States, 98109 | |
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Heart, Lung, and Blood Institute (NHLBI)
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Andrew Rezvani | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium |
| Responsible Party: | Joachim Deeg, Investigator, Fred Hutchinson Cancer Research Center |
| ClinicalTrials.gov Identifier: | NCT00445744 History of Changes |
| Other Study ID Numbers: |
2130.00 NCI-2010-00270 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) P01HL036444 ( U.S. NIH Grant/Contract ) |
| First Posted: | March 9, 2007 Key Record Dates |
| Results First Posted: | January 2, 2018 |
| Last Update Posted: | January 2, 2018 |
| Last Verified: | December 2017 |
Additional relevant MeSH terms:
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Syndrome Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Myelodysplastic Syndromes Preleukemia Neoplasm Metastasis Primary Myelofibrosis Polycythemia Polycythemia Vera Thrombocytosis Thrombocythemia, Essential Disease Pathologic Processes Neoplasms by Histologic Type |
Neoplasms Bone Marrow Diseases Hematologic Diseases Precancerous Conditions Neoplastic Processes Myeloproliferative Disorders Bone Marrow Neoplasms Hematologic Neoplasms Neoplasms by Site Blood Platelet Disorders Blood Coagulation Disorders Hemorrhagic Disorders Cyclophosphamide Methotrexate Tacrolimus |