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

NCT00445744 | Completed Results DMC

• 3 other identifiers: 2130.00NCI-2010-00270P01HL036444
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

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

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); 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

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Up to day 200

Study Arms (1)

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.

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

Interventions

cyclophosphamide DRUG

Given IV

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana

Treatment (cyclophosphamide, busulfan, transplant)

busulfan DRUG

Given IV

Also known as: BSF, BU, Misulfan, Mitosan, Myeloleukon

Treatment (cyclophosphamide, busulfan, transplant)

tacrolimus DRUG

Given IV or PO

Also known as: FK 506, Prograf

Treatment (cyclophosphamide, busulfan, transplant)

methotrexate DRUG

Given IV

Also known as: amethopterin, Folex, methylaminopterin, Mexate, MTX

Treatment (cyclophosphamide, busulfan, transplant)

cytogenetic analysis GENETIC

Correlative studies

Treatment (cyclophosphamide, busulfan, transplant)

flow cytometry OTHER

Correlative studies

Treatment (cyclophosphamide, busulfan, transplant)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (cyclophosphamide, busulfan, transplant)

pharmacogenomic studies OTHER

Correlative studies

Also known as: Pharmacogenomic Study

Treatment (cyclophosphamide, busulfan, transplant)

peripheral blood stem cell transplantation PROCEDURE

Undergo PBPC transplantation

Also known as: PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell

Treatment (cyclophosphamide, busulfan, transplant)

allogeneic hematopoietic stem cell transplantation PROCEDURE

Undergo allogeneic transplantation

Treatment (cyclophosphamide, busulfan, transplant)

Eligibility Criteria

• Age: Up to 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Congenital Abnormalities; Thrombocythemia, Essential; Chromosome 5q Deletion Syndrome; Polycythemia Vera; Primary Myelofibrosis; Leukemia, Myeloid, Acute

Interventions

Cyclophosphamide; Busulfan; Tacrolimus; Methotrexate; merphos; Cytogenetic Analysis; Flow Cytometry; Pharmacogenomic Testing; Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombocytosis; Blood Platelet Disorders; Myeloproliferative Disorders; Bone Marrow Diseases; Hemorrhagic Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Macrolides; Lactones; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Cell Separation; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry; Chemistry Techniques, Analytical; Genetic Testing; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: H. Joachim Deeg MD
• Organization: FHCRC

jdeeg@fhcrc.org

206 667 4409

Study Officials

• Andrew Rezvani

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Investigator

Study Record Dates

• First Submitted: March 7, 2007
• First Posted: March 9, 2007
• Study Start: December 1, 2006
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2013
• Last Updated: January 2, 2018
• Results First Posted: January 2, 2018

Record last verified: 2017-12

Locations

US (1)