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A Phase I Trial of Myeloablative Conditioning Using Clofarabine and High-Dose Busulfan for Patients With Refractory Hematological Malignancies Undergoing Allogeneic HSCT


Phase 1
18 Years
60 Years
Not Enrolling
Both
Hematologic Malignancies

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Trial Information

A Phase I Trial of Myeloablative Conditioning Using Clofarabine and High-Dose Busulfan for Patients With Refractory Hematological Malignancies Undergoing Allogeneic HSCT


All patients will receive the same dose of busulfan. The dose of clofarabine will be
escalated in successive cohorts of patients. Using a standard dose escalation design,
successive cohorts of 3 patients will be treated with escalating doses of clofarabine. At
the MTD (or highest dose-level if the MTD is not reached), the cohort will be expanded to 10
patients to better investigate correlative studies and give some preliminary idea of
efficacy.


Inclusion Criteria:



- Documentation of disease. Patients must have one of the following disease types:

- Acute myeloid leukemia (AML) with either:

- Primary refractory to induction chemotherapy

- Relapsed and refractory AML with >5% blasts in bone marrow or
extramedullary disease (excluding active disease of the central nervous
system).

- Patients in second or subsequent complete remission (CR2, CR3, etc.).

- Acute lymphoblastic leukemia (ALL) with one of the following criteria:

- Primary refractory to induction chemotherapy.

- Relapsed and refractory ALL with >5% blasts in bone marrow or
extramedullary disease (excluding active disease of the central nervous
system).

- Patients in second or subsequent complete remission (CR2, CR3, etc.).

- Myelodysplasia, refractory anemia with excess blasts with 11-20% blasts in the
bone marrow (RAEB II).

- Chronic myelogenous leukemia (CML) with one of the following criteria:

- Accelerated phase.

- Patients in blast crisis.

- Patients with aggressive non-Hodgkin's lymphoma (NHL), including diffuse large
cell lymphoma, mediastinal B-cell lymphoma, transformed lymphoma, mantle cell
lymphoma, and peripheral T cell lymphoma, who also have one of the following
criteria:

- Failure to achieve complete remission to primary induction therapy

- Relapsed NHL, refractory to at least one line of salvage systemic therapy

- Patients who relapse < 6 months following autologous stem cell transplantation are
not eligible.

- Patient age 18-60 years

- Availability of a consenting HLA-matched donor

- Performance status ECOG 0-1

- No active infection. Patients with active infections requiring oral or intravenous
antibiotics are not eligible for enrollment until resolution of infection.

- No HIV disease. Patients with immune dysfunction are at a significantly higher risk
of infection from intensive immunosuppressive therapies.

- Non-pregnant and non-nursing. Treatment under this protocol would expose a fetus to
significant risks. Women of childbearing potential should have a negative pregnancy
test prior to study entry. Women and men of reproductive potential should agree to
use an appropriate method of birth control throughout their participation in this
study due to the teratogenic potential of the therapy utilized in this trial.
Appropriate methods of birth control include oral contraceptives, implantable
hormonal contraceptives (Norplant®), or double barrier method (diaphragm plus
condom).

- Required baseline laboratory values:

- LVEF > 45% corrected

- DLCO > 50% of predicted value (corrected for hemoglobin)

- Serum creatinine ≤ 2.0 mg/dl or estimated creatinine clearance of ≥60 ml/min

- Bilirubin < 1 x upper limit of normal value

- AST and ALT < 1 x upper limit of normal value

- Signed written informed consent. Patient must be capable of understanding the
investigational nature of the investigational nature, potential risks and benefits of
the study, and able to provide valid informed consent.

Exclusion Criteria:

- Patients who relapse < 6 months following autologous stem cell transplantation are
not eligible

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Determine the MTD of clofarabine in association with a myeloablative dose of busulfan as a preparative regimen in patients with refractory hematological malignancies undergoing allogeneic HSCT.

Outcome Time Frame:

1 year

Safety Issue:

Yes

Principal Investigator

Sherif Farag, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Indiana University

Authority:

United States: Institutional Review Board

Study ID:

0704-30 IUCRO-0186

NCT ID:

NCT00477542

Start Date:

May 2007

Completion Date:

November 2010

Related Keywords:

  • Hematologic Malignancies
  • Clofarabine
  • allogeneic HSCT
  • refractory malignancies
  • Neoplasms
  • Hematologic Neoplasms

Name

Location

Indiana University Cancer CenterIndianapolis, Indiana  46202-5265