Researchers want to develop better ways to treat cancer. In this study, they will give
people with cancer two drugs. These drugs have been used on their own to treat some blood
To test the safety and efficacy of the drug combination of bortezomib and clofarabine.
Adults age 18 and over with advanced cancer that has progressed after receiving standard
treatment or that has no effective therapy.
Participants will be screened with medical history, physical exam, and scans to measure
their tumors. They will also have heart, blood, and urine tests. All of these may be
done by their regular doctors.
Participants will get the study drugs in 21-day cyles. They will stay at the clinic for
week 1 of every cycle, then have 2 weeks off.
<TAB>- Bortezomib will be injected under the skin on days 1 and 4.
<TAB>- Clofarabine will be injected in a vein for days 1-5.
During cycle 1 only, participants will go to the clinic or their doctor to have a
physical exam and blood tests at the start of the second and third week.
Participants will have clinical evaluations throughout the study, including before
receiving treatment and then before the start of each cycle.
Participants may stay in the study as long as they are tolerating the drugs and their
tumor is not getting worse.
Participants will have follow-up for 30 days after the last dose of study drugs.
The first part of this study tests the safety of different doses of clofarabine and
The second part of this study involves a separate group of participants who will undergo
mandatory research biopsies to learn more about the effects of clofarabine and
bortezomib on cancer cells.
The proteasome inhibitor bortezomib and purine nucleoside metabolic inhibitor clofarabine
demonstrated greater than additive activity in combination in preclinical xenograft models,
justifying the clinical evaluation of this combination for its antitumor activity
To establish the safety, tolerability, and maximum tolerated dose (MTD) of bortezomib
and clofarabine in patients with refractory solid tumors, lymphomas, or myelodysplastic
To determine the molecular effects of the clofarabine-bortezomib combination on
biomarkers of cell death and DNA damage in tumor biopsy tissue
To explore the mechanism of action of the bortezomib and clofarabine combination by
examining markers of DNA damage and apoptosis in tumor cells before and after treatment
-To characterize the changes in MDS residual disease burden that occur with bortezomib
and clofarabine treatment
Study participants must have histologically confirmed solid tumors or lymphomas or
myelodysplastic syndromes that have progressed on standard therapy known to prolong
survival or for which no standard treatment options exist
Age greater than or equal to 18
No major surgery, radiation, or chemotherapy within 3 weeks prior to entering the study
Adequate organ function
This is an open-label Phase I trial
The starting dose of clofarabine will be 1 mg/m2 administered intravenously on days 1
through 5 of a 21-day cycle; bortezomib will be administered at 0.8 mg/m2 subcutaneously
on days 1 and 4 of a 21-day cycle.
Dose escalation will follow a 3+3 design, with dose limiting toxicities defined during
Dose escalation will proceed in cohorts comprised of two separate groups of patients
(one group of patients with solid tumor/lymphoma and one group of patients with MDS),
with at least 1 from each group, until hematologic DLT or the second grade 2 hematologic
toxicity is observed, at which point, dose escalation will proceed separately for two
cohorts: (1) patients with solid tumors/lymphoma and (2) patients with MDS.
Up to 33 patients will be accrued to a PD expansi n cohort at the MTD to further assess
pharmacodynamic endpoints in tumor and blood.
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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