A Phase 1 interventional study of clofarabine and melphalan in Leukemia and Myelodysplastic Syndromes, sponsored by City of Hope Medical Center. Completed at 1 site in United States. Open to participants aged 1 Year to 120 Years. Per ClinicalTrials.gov, last updated 2023-06-15.
Sponsored by City of Hope Medical Center · Phase 1, Interventional, and Treatment
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.
OBJECTIVES:
OUTLINE: This is a dose-escalation study of clofarabine. Patients are stratified according to age (\< 18 years vs ≥ 18 years).
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.
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.
5,441 studies on the registry are indexed under Leukemia; 636 are open to participants now.
This study's enrollment of 20 is below the median of 38 across 4,247 interventional studies indexed under Leukemia.
Browse Leukemia studies →City of Hope Medical Center is the lead sponsor of 670 studies on the registry; 181 are open to participants now.
Of its 30 completed or terminated interventional studies of FDA-regulated products, 12 (40%) have results posted.
Counted across the registry records on this site, refreshed daily.
DISEASE CHARACTERISTICS:
Diagnosis of one of the following:
Disease meets 1 of the following criteria:
PATIENT CHARACTERISTICS:
No concurrent uncontrolled illness including, but not limited to, any of the following:
PRIOR CONCURRENT THERAPY:
Administered at the appropriate dose level(dose level one = 30 mg/m2, dose level two and three = 40 mg/m2)on days -9 to day -5 from transplant
Administered at the appropriate dose level (dose level one and two = 100 mg/m2, dose level three = 140 mg/m2) on day -4 from transplant
Peripheral blood draw on day -9 and day -4 prior to transplant
Peripheral blood draw on day -9 and day -4 prior to transplant
Bone marrow aspirate and biopsy to confirm diagnosis prior to transplant, day -9 pre-transplant, day 30 post-transplant, day 100 post-transplant, 6 months post-transplant, one year post-transplant, then yearly through year 5 post-transplant
Peripheral blood draw day -9 or earlier pre-transplant, day 14 post-transplant, day 30 post-transplant, day 60 post-transplant, day 100 post-transplant, 6 months and one year post-transplant.
Infusion of allogeneic hematopoietic stem cells on day 0 of transplant
Maximum tolerated dose
Time frame: 4 weeks from the start of treatment
Dose-limiting toxicity as assessed by NCI CTCAE v3.0 and the Modified Bearman scale
Time frame: 4 weeks from the start of treatment
Graft failure or rejection
Time frame: 35 days post-transplant
Efficacy
Time frame: One year post-transplant
Correlative laboratory studies of engraftment, immune reconstitution, and therapeutic outcomes
Time frame: One year post-transplant
This study is completed, as verified in Jun 2023. You cannot join it, but the record below documents what was studied.
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City of Hope Medical Center