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Cyclophosphamide Followed by Intravenous Busulfan as Conditioning for Hematopoietic Cell Transplantation in Patients With Myelofibrosis, Acute Myeloid Leukemia, or Myelodysplastic Syndrome.


N/A
N/A
65 Years
Open (Enrolling)
Both
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

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Trial Information

Cyclophosphamide Followed by Intravenous Busulfan as Conditioning for Hematopoietic Cell Transplantation in Patients With Myelofibrosis, Acute Myeloid Leukemia, or Myelodysplastic Syndrome.


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.


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)

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Effectiveness of cyclophosphamide/busulfan regimen in reducing regimen-related toxicity

Outcome Description:

Diagnoses will be made according to the established criteria initially proposed in 1984 by McDonald et al.

Outcome Time Frame:

Up to day +20

Safety Issue:

Yes

Principal Investigator

Andrew Rezvani

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Authority:

United States: Institutional Review Board

Study ID:

2130.00

NCT ID:

NCT00445744

Start Date:

December 2006

Completion Date:

Related Keywords:

  • 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
  • Congenital Abnormalities
  • Primary Myelofibrosis
  • Neoplasms
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia
  • Polycythemia
  • Polycythemia Vera
  • Thrombocythemia, Essential
  • Thrombocytosis

Name

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattle, Washington  98109