NeoplasmsPhase 1NCT02211755
Trial of the Combination of Bortezomib and Clofarabine in Adults With Relapsed Solid Tumors
A Phase 1 study testing Bortezomib plus Clofarabine in people with Neoplasms and Myelodysplastic Syndromes, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: 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 cell cancers. Objectives: To test the safety and efficacy of the drug combination of bortezomib and clofarabine. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Neoplasms, Myelodysplastic Syndromes, Lymphomas
- What is being tested?
- Bortezomib plus Clofarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Oct 2014to 15 Aug 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Sensory/motor neuropathy >= Grade 2
- QTc interval (Fridericia formula) > 450 msec for men or > 470 msec for women at study entry; history of congenital long QT syndrome
- Patients who are receiving any other investigational agents.
- Patients with active brain metastases, CNS disease, or carcinomatous meningitis are excluded from this clinical trial. Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no
- evidence of progression.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs. Patients who have previously received either clofarabine or bortezomib will be excluded as this may affect accurate determination of the MTD.
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- Uncontrolled intercurrent illness including, but not limited to, serious untreated infection, symptomatic respiratory failure/congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women are excluded from this study because bortezomib and clofarabine have been assigned to pregnancy category D by the FDA. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the study drugs, breastfeeding should be discontinued prior to the first dose of study drug and women should refrain from nursing throughout the treatment period and for 3 months following the last dose of study drug.
- HIV-positive patients on combination antiretroviral therapy are ineligible because of possible pharmacokinetic interactions with study drugs.
- Both men and women of all races and ethnic groups are eligible for this trial.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Phase I Trial of the Combination of Bortezomib and Clofarabine in Adults With Refractory Solid Tumors, Lymphomas, or Myelodysplastic Syndromes
Background:
- 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 cell cancers.
Read more
Objectives:
- To test the safety and efficacy of the drug combination of bortezomib and clofarabine.
Eligibility:
- Adults age 18 and over with advanced cancer that has progressed after receiving standard treatment or that has no effective therapy.
Design:
- 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 bortezomib.
- 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.
Read the detailed description
BACKGROUND:
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
OBJECTIVES:
To establish the safety, tolerability, and maximum tolerated dose (MTD) of bortezomib and clofarabine in patients with refractory solid tumors, lymphomas, or myelodysplastic syndromes (MDS)
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 circulating tumor cells before and after treatment
To characterize the changes in MDS residual disease burden that occur with bortezomib and clofarabine treatment
To examine genomic alterations in circulating tumor DNA (ctDNA) that may be associated with response or resistance to clofarabine-bortezomib combination treatment.
ELIGIBILITY:
- 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
STUDY DESIGN:
- 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 cycle 1.
- 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.
- Conditions
- Neoplasms, Myelodysplastic Syndromes, Lymphomas
- Being tested
- Bortezomib plus Clofarabine
- Keywords
- Purine Nucleoside Inhibitor, Proteasome Inhibitor, Combination Treatment, Solid Tumors, Hematologic
- Medical subject headings
- Neoplasms, Myelodysplastic Syndromes, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bortezomib plus ClofarabineDrug
The proteasome inhibitor bortezomib and purine nucleoside metabolic inhibitor clofarabine demonstrated greater than additive activity in combination in preclinical xenograft models
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Starting doses are clofarabine at 1 mg/m2 IV on days 1 through 5 of a 21-day cycle, and bortezomib at 0.8 mg/m2 subcutaneously on days 1 and 4 of a 21-day cycle. Receives: Drug: Bortezomib plus Clofarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and MTD
To establish the safety, tolerability, and maximum tolerated dose (MTD) of bortezomib and clofarabine in patients with refractory solid tumors or lymphomas or myelodysplastic syndromes
Measured: Cycle 1 (21 days)
Secondary outcomes (2)
Biomarkers of DNA damage and apoptosis in circulating tumor cells
To determine the effects of the clofarabine-bortezomib combination on biomarkers of DNA damage and apoptosis in circulating tumor cells
Measured: Baseline, cycle 1 day 1, and cycle 2 day 1
Biomarkers of cell death and DNA damage in tumor biopsy tissue
To determine the effects of the clofarabine-bortezomib combination on biomarkers of cell death and DNA damage in tumor biopsy tissue
Measured: Baseline, cycle 1 day 1, and cycle 2 day 4/day 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2014 (estimated)
- Study start6 Oct 2014
- Primary completion14 Aug 2025
- Study completion15 Aug 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Alice P Chen, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02211755
- Sponsor's protocol ID
- 140161
- Other IDs
- 14-C-0161
- Status last verified
- Apr 2026
- First submitted
- 6 Aug 2014
- Last updated
- 28 Apr 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Duechler M, Linke A, Cebula B, Shehata M, Schwarzmeier JD, Robak T, Smolewski P. In vitro cytotoxic effect of proteasome inhibitor bortezomib in combination with purine nucleoside analogues on chronic lymphocytic leukaemia cells. Eur J Haematol. 2005 May;74(5):407-17. doi: 10.1111/j.1600-0609.2004.00406.x.
PubMed 15813915Kummar S, Chen HX, Wright J, Holbeck S, Millin MD, Tomaszewski J, Zweibel J, Collins J, Doroshow JH. Utilizing targeted cancer therapeutic agents in combination: novel approaches and urgent requirements. Nat Rev Drug Discov. 2010 Nov;9(11):843-56. doi: 10.1038/nrd3216. Epub 2010 Oct 29.
PubMed 21031001
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of the Combination of Bortezomib and Clofarabine in Adults With Refractory Solid Tumors, Lymphomas, or Myelodysplastic Syndromes
- ClinicalTrials.gov ID
- NCT02211755
- Acronym / sponsor ID
- 140161
- Conditions
- Neoplasms, Myelodysplastic Syndromes, Lymphomas
- Keywords
- Purine Nucleoside Inhibitor, Proteasome Inhibitor, Combination Treatment, Solid Tumors, Hematologic
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 6 Oct 2014 (actual)
- Primary completion
- 14 Aug 2025 (actual)
- Study completion
- 15 Aug 2025 (actual)
- First posted
- 7 Aug 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- 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 cell cancers.
Objectives:
- To test the safety and efficacy of the drug combination of bortezomib and clofarabine.
Eligibility:
- Adults age 18 and over with advanced cancer that has progressed after receiving standard treatment or that has no effective therapy.
Design:
- 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 bortezomib.
- 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.
Detailed description
BACKGROUND:
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
OBJECTIVES:
To establish the safety, tolerability, and maximum tolerated dose (MTD) of bortezomib and clofarabine in patients with refractory solid tumors, lymphomas, or myelodysplastic syndromes (MDS)
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 circulating tumor cells before and after treatment
To characterize the changes in MDS residual disease burden that occur with bortezomib and clofarabine treatment
To examine genomic alterations in circulating tumor DNA (ctDNA) that may be associated with response or resistance to clofarabine-bortezomib combination treatment.
ELIGIBILITY:
- 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
STUDY DESIGN:
- 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 cycle 1.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Bortezomib plus ClofarabineStarting doses are clofarabine at 1 mg/m2 IV on days 1 through 5 of a 21-day cycle, and bortezomib at 0.8 mg/m2 subcutaneously on days 1 and 4 of a 21-day cycle. |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (10 listed)
- Sensory/motor neuropathy >= Grade 2
- QTc interval (Fridericia formula) > 450 msec for men or > 470 msec for women at study entry; history of congenital long QT syndrome
- Patients who are receiving any other investigational agents.
- Patients with active brain metastases, CNS disease, or carcinomatous meningitis are excluded from this clinical trial. Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no
- evidence of progression.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bortezomib plus ClofarabineThe proteasome inhibitor bortezomib and purine nucleoside metabolic inhibitor clofarabine demonstrated greater than additive activity in combination in preclinical xenograft models | Drug | 1 |
Primary outcome
Safety and MTD
Time frame: Cycle 1 (21 days)
To establish the safety, tolerability, and maximum tolerated dose (MTD) of bortezomib and clofarabine in patients with refractory solid tumors or lymphomas or myelodysplastic syndromes
2 secondary outcomes
Biomarkers of DNA damage and apoptosis in circulating tumor cells
Time frame: Baseline, cycle 1 day 1, and cycle 2 day 1
Biomarkers of cell death and DNA damage in tumor biopsy tissue
Time frame: Baseline, cycle 1 day 1, and cycle 2 day 4/day 5
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2026.
- Background: PubMed 15813915Duechler M, Linke A, Cebula B, Shehata M, Schwarzmeier JD, Robak T, Smolewski P. In vitro cytotoxic effect of proteasome inhibitor bortezomib in combination with purine nucleoside analogues on chronic lymphocytic leukaemia cells. Eur J Haematol. 2005 May;74(5):407-17. doi: 10.1111/j.1600-0609.2004.00406.x.
- Background: PubMed 21031001Kummar S, Chen HX, Wright J, Holbeck S, Millin MD, Tomaszewski J, Zweibel J, Collins J, Doroshow JH. Utilizing targeted cancer therapeutic agents in combination: novel approaches and urgent requirements. Nat Rev Drug Discov. 2010 Nov;9(11):843-56. doi: 10.1038/nrd3216. Epub 2010 Oct 29.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alice P Chen, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Bortezomib plus Clofarabine in people with Neoplasms and Myelodysplastic Syndromes, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and MTD (time frame: Cycle 1 (21 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02211755, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Apr 2026.