Cyclophosphamide and Busulfan Followed By Donor Stem Cell Transplant in Treating Patients With Myelofibrosis - Full Text View

Sponsors and Collaborators:	Fred Hutchinson Cancer Research Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00445744

Purpose

RATIONALE: Giving chemotherapy, such as cyclophosphamide and busulfan, before a donor stem cell transplant helps stop the growth of abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy 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 methotrexate after the transplant may stop this from happening.

PURPOSE: This phase I/II trial is studying the side effects of cyclophosphamide and busulfan followed by donor stem cell transplant and to see how well they work in treating patients with myelofibrosis.

Condition	Intervention	Phase
Cancer-Related Problem/Condition Chronic Myeloproliferative Disorders	Drug: busulfan Drug: cyclophosphamide Drug: methotrexate Drug: tacrolimus Procedure: allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation Procedure: pharmacological study	Phase I Phase II

MedlinePlus related topics: Cancer Spleen Diseases

Drug Information available for: Cyclophosphamide Methotrexate Tacrolimus Tacrolimus anhydrous Busulfan

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	Cyclophosphamide Followed by Intravenous Busulfan as Conditioning for Hematopoietic Cell Transplantation in Patients With Myelofibrosis: a Phase I/II Study

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Rate of hepatotoxicity [ Designated as safety issue: Yes ]
Nonrelapse mortality at day 200 [ Designated as safety issue: No ]
Graft failure [ Designated as safety issue: No ]
Time to engraftment [ Designated as safety issue: No ]
Peak bilirubin at day 20 [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Incidence and severity of graft-versus-host disease [ Designated as safety issue: No ]

Secondary Outcome Measures:

Progression-free survival [ Designated as safety issue: No ]
Relapse rate [ Designated as safety issue: No ]
Pulmonary toxicity [ Designated as safety issue: Yes ]

Estimated Enrollment:	30
Study Start Date:	December 2006
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine the incidence of hepatotoxicity, in terms of incidence of severe/moderate sinusoidal obstruction syndrome or peak bilirubin greater than 4.0 mg/dL, in patients with idiopathic myelofibrosis treated with cyclophosphamide and busulfan followed by allogeneic hematopoietic stem cell transplantation (HSCT).

Secondary

Determine overall and nonrelapsed mortality at day 200 after HSCT in patients treated with this regimen.
Determine peak bilirubin levels at day 20 after HSCT in patients treated with this regimen.
Determine the incidence of pulmonary toxicity in the form of idiopathic pneumonia syndrome in patients treated with this regimen.
Determine the rate of graft failure in patients treated with this regimen.
Determine the time to engraftment in patients treated with this regimen.
Determine the rate of relapse in patients treated with this regimen.
Determine the incidence and severity of graft-versus-host disease in patients treated with this regimen.
Evaluate the pharmacokinetics/dynamics of this regimen.
Determine the pharmacogenomics (e.g., CYP2B6, GSTA1, Sp110) of response, toxicity, and pharmacokinetics of this regimen.

OUTLINE: This is a prospective, multicenter study.

Conditioning and transplantation: Patients receive cyclophosphamide IV on days -7 and -6 and busulfan IV over 3 hours on days -5 to -2. Patients undergo allogeneic peripheral blood stem cell transplantation on day 0.
Graft-versus-host disease prophylaxis: Patients receive tacrolimus IV continuously or orally twice daily beginning on day -1 and continuing until day 200 and methotrexate IV on days 1, 3, 6, and 11.

Blood samples are obtained periodically for pharmacokinetic and pharmacogenomic studies.

After the completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	up to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of chronic idiopathic myelofibrosis OR myelofibrosis developing with polycythemia vera or essential thrombocythemia
HLA-identical or 1-allele-mismatched related or unrelated donor of unmanipulated peripheral blood stem cells available

PATIENT CHARACTERISTICS:

Karnofsky performance status 80-100%
Life expectancy not limited by diseases other than myelofibrosis
AST < 2 times upper limit of normal (ULN)
Bilirubin ≤ 2 times ULN
Creatinine ≤ 2 times ULN
Creatinine clearance ≥ 50% of expected
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No HIV positivity
No active infectious hepatitis
No known hypersensitivity to cyclophosphamide or busulfan
No hepatic dysfunction, such as synthetic dysfunction or cirrhosis
No dialysis dependence
No impaired pulmonary function, indicated by 1 of the following:
- pO2 < 70 mm Hg and DLCO < 70% predicted
- pO2 < 80 mm Hg and DLCO < 60% predicted
- Receiving continuous supplementary oxygen
No impaired cardiac function, as evidenced by ejection fraction < 35% OR active coronary artery disease

PRIOR CONCURRENT THERAPY:

No concurrent medications known to strongly inhibit enzymes in the CYP450 pathway
No concurrent aprepitant
No concurrent acetylsalicylic acid or nonsteroidal anti-inflammatory drugs

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00445744

Locations

United States, Washington
Fred Hutchinson Cancer Research Center	Recruiting
Seattle, Washington, United States, 98109
Contact: Andrew Rezvani, MD 206-667-1505 arezvani@fhcrc.org
Seattle Cancer Care Alliance	Recruiting
Seattle, Washington, United States, 98109-1023
Contact: Clinical Trials Office - Seattle Cancer Care Alliance 800-804-8824

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Andrew Rezvani, MD

Fred Hutchinson Cancer Research Center

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Responsible Party:	Fred Hutchinson Cancer Research Center ( Andrew Rezvani )
Study ID Numbers:	CDR0000531158, FHCRC-2130.00
Study First Received:	March 7, 2007
Last Updated:	December 31, 2008
ClinicalTrials.gov Identifier:	NCT00445744
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

chronic idiopathic myelofibrosis
essential thrombocythemia
polycythemia vera
secondary myelofibrosis

Study placed in the following topic categories:

Essential thrombocytosis
Polycythemia
Polycythemia Vera
Myelofibrosis
Hematologic Diseases
Myeloproliferative Disorders
Tacrolimus
Cyclophosphamide
Polycythemia vera
Folic Acid
Myeloid Metaplasia

Myelofibrosis-osteosclerosis
Lymphatic Diseases
Busulfan
Hemorrhagic thrombocythemia
Metaplasia
Chronic Myeloproliferative Disorders
Neoplasm Metastasis
Thrombocytosis
Methotrexate
Thrombocythemia, Hemorrhagic
Bone Marrow Diseases

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Reproductive Control Agents
Folic Acid Antagonists
Abortifacient Agents, Nonsteroidal
Immunosuppressive Agents

Pharmacologic Actions
Therapeutic Uses
Abortifacient Agents
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Dermatologic Agents
Splenic Diseases
Alkylating Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on January 16, 2009