Cyclophosphamide and Busulfan Followed by Donor Stem Cell Transplant in Treating Patients With Myelofibrosis, Acute Myeloid Leukemia, or Myelodysplastic Syndrome

NCT ID: NCT00445744

Last Updated: 2018-01-02

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

52 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-12-31

Study Completion Date

2013-06-30

Brief Summary

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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

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Detailed Description

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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.

Conditions

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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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

cyclophosphamide

Intervention Type DRUG

Given IV

busulfan

Intervention Type DRUG

Given IV

tacrolimus

Intervention Type DRUG

Given IV or PO

methotrexate

Intervention Type DRUG

Given IV

cytogenetic analysis

Intervention Type GENETIC

Correlative studies

flow cytometry

Intervention Type OTHER

Correlative studies

pharmacological study

Intervention Type OTHER

Correlative studies

pharmacogenomic studies

Intervention Type OTHER

Correlative studies

peripheral blood stem cell transplantation

Intervention Type PROCEDURE

Undergo PBPC transplantation

allogeneic hematopoietic stem cell transplantation

Intervention Type PROCEDURE

Undergo allogeneic transplantation

Interventions

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cyclophosphamide

Given IV

Intervention Type DRUG

busulfan

Given IV

Intervention Type DRUG

tacrolimus

Given IV or PO

Intervention Type DRUG

methotrexate

Given IV

Intervention Type DRUG

cytogenetic analysis

Correlative studies

Intervention Type GENETIC

flow cytometry

Correlative studies

Intervention Type OTHER

pharmacological study

Correlative studies

Intervention Type OTHER

pharmacogenomic studies

Correlative studies

Intervention Type OTHER

peripheral blood stem cell transplantation

Undergo PBPC transplantation

Intervention Type PROCEDURE

allogeneic hematopoietic stem cell transplantation

Undergo allogeneic transplantation

Intervention Type PROCEDURE

Other Intervention Names

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CPM CTX Cytoxan Endoxan Endoxana BSF BU Misulfan Mitosan Myeloleukon FK 506 Prograf amethopterin Folex methylaminopterin Mexate MTX pharmacological studies Pharmacogenomic Study PBPC transplantation PBSC transplantation peripheral blood progenitor cell transplantation transplantation, peripheral blood stem cell

Eligibility Criteria

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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)
Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Joachim Deeg

Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Andrew Rezvani

Role: PRINCIPAL_INVESTIGATOR

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Locations

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Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-2010-00270

Identifier Type: REGISTRY

Identifier Source: secondary_id

P01HL036444

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2130.00

Identifier Type: -

Identifier Source: org_study_id

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