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Phase I/II Study of Myeloablative Allogeneic Stem Cell Transplantation for Aggressive Hematologic Malignancies Using Clofarabine and Busulfan x 4 (Clo/BU4) Regimen


Phase 1/Phase 2
N/A
70 Years
Open (Enrolling)
Both
Leukemia, Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Multiple Myeloma, Myelodysplastic Syndrome

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Trial Information

Phase I/II Study of Myeloablative Allogeneic Stem Cell Transplantation for Aggressive Hematologic Malignancies Using Clofarabine and Busulfan x 4 (Clo/BU4) Regimen


Transplants with stem cells collected from the blood of an unrelated donor (allo-HSCT) are
being used more commonly for many blood cancers which are not curable with more conventional
methods of chemotherapy. Although allo-HSCT has great potential, there are still high risks
due to infections, graft-versus-host disease (GVHD), where the donor's cells attack the
recipient's tissues as foreign, and due to toxic effects of the chemotherapy drugs given to
prepare (or condition) the recipient's bone marrow for transplant.

As a reduced intensity conditioning, a combination of Fludarabine and a lower dose of
Busulfan (Flu/BU2) is one of the most popular regimens. Among full-intensity regimens, a
combination of Fludarabine and standard-dose Busulfan (Flu/BU4) has been investigated
recently and shown to be very well tolerated.

Clofarabine, similar to Fludarabine, is known to have a stronger anti-tumor effect than
Fludarabine and has shown promise in treating aggressive acute leukemias. In addition,
evidence is that it is well-tolerated with manageable side effects especially in older
subjects. Thus replacing Fludarabine with Clofarabine in a full-intensity transplant
regimen, Clo/BU4 may provide a regimen with increased anti-tumor activity without adding
significant risks of toxicity.

The goals of the study are (Phase I) to determine the appropriate dose for Clofarabine with
Busulfan as a full-intensity regimen (Clo/BU4) and then (Phase II) to investigate the safety
and effectiveness of this regimen as a conditioning for HSCT in the treatment for aggressive
hematologic malignancies, in subjects where more conventional approaches are failing.


Inclusion Criteria:



Disease Criteria

- Acute leukemia or chronic myelogenous leukemia in blastic crisis or accelerated
phase, not in remission at the time of transplant

- Myelodysplastic syndrome, with more than 5% blasts in bone marrow at the time of
transplant

- Hodgkin and Non-Hodgkin Lymphomas: Not in CR in PET scan or CT scan before
transplant, or relapsed within 1 year from previous remission

- CLL not in remission

- Multiple Myeloma, not in remission

- Suitable donor available (related or unrelated)

Age, Organ Function Criteria

- Age: ≤ 70 years

- Cardiac: LV Ejection Fraction ≥ 40% by MUGA or Echocardiogram

- Pulmonary: FEV1 and FVC ≥ 40% predicted, and DLCO (corrected for hemoglobin) ≥ 40% of
predicted

- Renal: Adult population: serum creatinine ≤ 1.0 mg/dL (if serum creatinine > 1.0
mg/dL, then the estimated glomerular filtration rate (GFR) must be > 60 mL/min/1.73
m2 as calculated by the Modification of Diet in Renal Disease equation)

- Renal: Pediatric population: serum creatinine clearance ≥ 90 ml/min/1.73 m2 as
calculated by the Schwartz formula for estimated GFR

- Hepatic: serum total bilirubin ≤ 2.0 mg/dl and AST / ALT ≤ ULN x 4

- Performance status: Karnofsky ≥ 70%

Exclusion Criteria:

- Other active life-threatening cancer requiring treatment other than allo-HSCT

- HIV1 or HIV2 positive

- Uncontrolled medical or psychiatric disorder

- Uncontrolled viral or fungal infection

- Active CNS leukemia

- Non-compliant to medications

- No appropriate caregivers identified

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

To establish the toxicity profile of three doses of Clofarabine in combination with Busulfan and assess the one-year overall survival rate for subjects receiving the dose of Clofarabine with a DLT rate closest to 20%.

Outcome Time Frame:

one year

Safety Issue:

Yes

Principal Investigator

John Magenau, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Michigan, Department of Internal Medicine, Blood and Marrow Transplant Program

Authority:

United States: Institutional Review Board

Study ID:

UMCC 2007.055

NCT ID:

NCT00556452

Start Date:

October 2007

Completion Date:

September 2012

Related Keywords:

  • Leukemia
  • Hodgkin Lymphoma
  • Non-Hodgkin Lymphoma
  • Multiple Myeloma
  • Myelodysplastic Syndrome
  • Hodgkin Disease
  • Leukemia
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Myelodysplastic Syndromes
  • Preleukemia
  • Hematologic Neoplasms

Name

Location

University of Michigan, Department of Internal Medicine, Blood and Marrow Transplant ProgramAnn Arbor, Michigan  48170