Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT00641030 |
Other study ID # |
06114 |
Secondary ID |
P30CA033572CHNMC |
Status |
Completed |
Phase |
Phase 1
|
First received |
|
Last updated |
|
Start date |
July 2007 |
Est. completion date |
January 2011 |
Study information
Verified date |
June 2023 |
Source |
City of Hope Medical Center |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
RATIONALE: Giving chemotherapy, such as clofarabine and melphalan, before a donor stem cell
transplant helps stop the growth of cancer or 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 cyclosporine
and mycophenolate mofetil after the transplant may stop this from happening.
PURPOSE: This phase I trial is studying the side effects and best dose of clofarabine when
given together with high-dose melphalan followed by a donor stem cell transplant in treating
patients with acute myeloid leukemia, acute lymphocytic leukemia, or myelodysplastic
syndromes.
Description:
OBJECTIVES:
- To determine the maximum tolerated dose and toxicities of clofarabine when administered
with high-dose melphalan as a conditioning regimen in patients undergoing allogeneic
stem cell transplantation for acute myeloid leukemia, acute lymphocytic leukemia, or
myelodysplastic syndromes.
- To assess the efficacy of this regimen in facilitating engraftment in these patients.
- To perform correlative laboratory studies of engraftment, immune reconstitution, and
therapeutic outcomes.
OUTLINE: This is a dose-escalation study of clofarabine. Patients are stratified according to
age (< 18 years vs ≥ 18 years).
- Reduced-intensity conditioning regimen: Patients receive clofarabine IV over 30 minutes
on days -9 to -5 and high-dose melphalan IV over 30 minutes on day -4.
Cohorts of 3-6 patients receive escalating doses of clofarabine until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.
- Allogeneic stem cell transplantation: Patients undergo allogeneic stem cell
transplantation on day 0.
- Graft-versus-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV over 10
hours or orally twice daily beginning on day -1 and continuing until day 90-100,
followed by a taper in the absence of GVHD. Patients also receive mycophenolate mofetil
IV or orally twice daily beginning on day 0 and continuing until day 28, followed by a
taper in the absence of GVHD.
Patients undergo blood and/or bone marrow sample collection periodically for correlative
laboratory studies. Samples are examined for markers of immune reconstitution (i.e., CD8+ T
lymphocytes, CD4+ T lymphocytes, NK cells, B cells, and monocytes) by flow cytometry and for
diversity of the reconstituted T-cell repertoire by PCR-based T-cell receptor repertoire
analysis. Samples are also examined for gene expression of hRRM2 and markers of apoptosis
(i.e., Bcl-2, Bid, NFkB2, and Bcl-3) by real-time RT-PCR and for markers of ribonucleotide
reductase inhibition (i.e., dCTP levels in circulating peripheral blood mononuclear cells).
After completion of study therapy, patients are followed periodically for up to 5 years.