LeukemiaPhase 1NCT00882076
Clofarabine, Etoposide, and Mitoxantrone for Relapsed and Refractory Acute Leukemias
A Phase 1 study testing Clofarabine, Mitoxantrone and Etoposide in people with Leukemia, run by Milton S. Hershey Medical Center at 1 site in United States.
Trial summary
The purpose of this study is to establish toxicity and a maximum tolerated dose recommended phase 2 dose of Clofarabine in combination with Etoposide and Mitoxantrone for therapy of relapsed or refractory acute leukemias. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Leukemia
- What is being tested?
- Clofarabine, Mitoxantrone and Etoposide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2009to Mar 2011
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adequate renal and hepatic function.
- Capable of understanding the investigational nature, potential risks and benefits of the study and able to provide valid informed consent.
- Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment.
- Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.
- LVEF must be ≥ 50% within 2 weeks.
Who cannot join
- Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.
- Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea. The patient must have recovered from all acute toxicities from any previous therapy.
- Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver or other organ system that may place the patient at undue risk to undergo treatment.
- Patients with a systemic fungal, bacterial, viral, or other infection not controlled.
- Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow-up or interpretation of study results.
- Have had a diagnosis of another malignancy, unless the patient has been disease free for at least 3 years following the completion of curative intent therapy with the following exceptions: patients with treated non-melanoma skin cancer, in situ carcinoma or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for the study if definitive treatment for the condition has been completed. Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen values are also eligible for this study if hormonal therapy has been initiated or a radical prostatectomy has been performed. Additionally, patients with prostate cancer treated with radiation therapy are also eligible for the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
Penn State Hershey Cancer Institute
Hershey, Pennsylvania, 17033
About this study
The purpose of this study is to establish toxicity and a maximum tolerated dose recommended phase 2 dose of Clofarabine in combination with Etoposide and Mitoxantrone for therapy of relapsed or refractory acute leukemias. The investigators will observe responses with these therapy agents and assess the impact of Clofarabine interacting with Etoposide in induction of DNA strand breaks.
Read the detailed description
This will be a phase I study with a standard 3x3 design. Patients will proceed to treatment through a series of cohorts with the three drugs being delivered over five days beginning with a dose of Etoposide 100 mg/m2 on days 1-5,Mitoxantrone 8 mg/m2 days 1-3, and clofarabine at 20 mg/m2 IV on days 2-6. Presuming this and subsequent cohorts are tolerable and no more than 1 patient per cohort develops DLT, MTD patients will be treated in cohorts of 3-6 patients up to a final dose level of Etoposide 100 mg/m2 on days 1-5,Mitoxantrone 8 mg/m2 days 1-5, and Clofarabine at 30 mg/m2 IV on days 2-6. Patients failing to enter remission may receive 4 days of therapy with Etoposide 100 mg/m2 on days 1-4,Mitoxantrone 8 mg/m2 days 1-2 or 1-4,and Clofarabine at 20-30 mg/m2 IV on days 1-4. According to established definitions for dose limiting toxicity a recommended phase II dose will be established. After this is established the final cohort will be expanded to 15 patients.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClofarabineDrug
Also called Clolar
For Treatment Clofarabine will be administered on Days 2-6 at the dose of 20mg/m2 in Cohort 1, 25mg/m2 in Cohort 2 and 30mg/m2 in Cohort 3 and 4 and 10mg/m2 in Cohort 0 (In the event of excessive DLT in Treatment Cohort 1). For Retreatment Clofarabine will be administered on Days 1-4 at the dose of 20mg/m2 in Cohort 1, 25mg/m2 in Cohort 2 and 30mg/m2 in Cohort 3 and 4 and 10mg/m2 in Cohort 0 (In the event of excessive DLT in Retreatment Cohort 1).
MitoxantroneDrug
Also called Mitoxantrone hydrochloride
For Treatment Mitoxantrone will be administered on Days 1-3 at the dose of 8mg/m2 in Cohort 1, 2, 3 and on Days 1-5 for Cohort 4 and on Days 1-3 8mg/m2 in Cohort 0 (In the event of excessive DLT in Treatment Cohort 1). For Retreatment Mitoxantrone will be administered on Days 1-2 (2 doses) at the dose of 8mg/m2 in Cohort 1, 2 and 3 and on Days 1-4 (4 doses) at the dose of 8mg/m2 in Cohort 4, and on Days 1-2 (2 doses) at the dose of 8mg/m2 in Cohort 0 (In the event of excessive DLT in Retreatment Cohort 1).
EtoposideDrug
Also called Etoposide Phosphate
For Treatment Etoposide will be administered on Days 1-5 at the dose of 100mg/m2 in Cohort 1, 2, 3, 4 and Cohort 0 (in the event of excessive DLT in Treatment Cohort 1). For Retreatment Etoposide will be administered on Days 1-4 at the dose of 100mg/m2 in Cohort 1, 2, 3, 4 and Cohort 0 (in the event of excessive DLT in Retreatment Cohort 1).
| Study group | Role | What they receive |
|---|---|---|
| Treatment Cohort 1 | Experimental | Etoposide (Days 1-5) 100 mg/m2; Mitoxantrone (Days 1-3) 8 mg/m2 (3 doses); Clofarabine (Days 2-6) 20 mg/m2 Receives: Drug: Clofarabine; Drug: Mitoxantrone; Drug: Etoposide |
| Treatment Cohort 2 | Experimental | Etoposide (Days 1-5) 100 mg/m2; Mitoxantrone (Days 1-3) 8 mg/m2; Clofarabine (Days 2-6) 25 mg/m2 Receives: Drug: Clofarabine; Drug: Mitoxantrone; Drug: Etoposide |
| Treatment Cohort 3 | Experimental | Etoposide (Days 1-5) 100 mg/m2; Mitoxantrone (Days 1-3) 8 mg/m2; Clofarabine (Days 2-6) 30 mg/m2 Receives: Drug: Clofarabine; Drug: Mitoxantrone; Drug: Etoposide |
| Treatment Cohort 4 | Experimental | Etoposide (Days 1-5) 100 mg/m2; Mitoxantrone (Days 1-5) 8 mg/m2; Clofarabine (Days 2-6) 30 mg/m2 Receives: Drug: Clofarabine; Drug: Mitoxantrone; Drug: Etoposide |
| Treatment Cohort 0 | Experimental | Etoposide (Days 1-5) 100 mg/m2; Mitoxantrone (Days 1-3) 8 mg/m2; Clofarabine (Days 2-6) 10 mg/m2 (In the event of a DLT in Treatment Cohort 1) Receives: Drug: Clofarabine; Drug: Mitoxantrone; Drug: Etoposide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Establish toxicity of Clofarabine in combination with Etoposide and Mitoxantrone for therapy of relapsed or refractory acute leukemias
Measured: Days 30-45
Establish dose limiting toxicity of Clofarabine in combination with Etoposide and Mitoxantrone for therapy of relapsed or refractory acute leukemias
Measured: Days 30-45
Establish maximum tolerated dose recommend Phase 2 dose of Clofarabine in combination with Etoposide and Mitoxantrone for therapy of relapsed or refractory acute leukemias
Measured: Days 30-45
Secondary outcomes (2)
Observe response of relapsed or refractory acute leukemias to therapy with these agents.
Measured: 30-70 days
Assess the impact of Clofarabine interacting with Etoposide and Mitoxantrone in induction of DNA strand breaks
Measured: 30-45 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2009 (estimated)
- Study startMar 2009
- Primary completionMar 2011
- Study completionMar 2011
Why it stopped: study closed prematurely
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by Milton S. Hershey Medical CenterThe 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
- Non-randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Milton S. Hershey Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David F. Claxton, MD, Milton S. Hershey Medical Center
- Investigators
- David F. Claxton, MD, Principal investigator, Penn State College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00882076
- Sponsor's protocol ID
- PSHCI 08-096
- Status last verified
- Jul 2019
- First submitted
- 15 Apr 2009
- Last updated
- 24 Jul 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Determine if data is valuable
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clofarabine, Etoposide, and Mitoxantrone for Relapsed and Refractory Acute Leukemias
- ClinicalTrials.gov ID
- NCT00882076
- Acronym / sponsor ID
- PSHCI 08-096
- Conditions
- Leukemia
- Keywords
- acute lymphoblastic leukemia, chronic lymphocytic leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: study closed prematurely
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Milton S. Hershey Medical CenterUniversity, hospital or other
- Study start
- Mar 2009
- Primary completion
- Mar 2011 (actual)
- Study completion
- Mar 2011 (actual)
- First posted
- 16 Apr 2009 (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.
The purpose of this study is to establish toxicity and a maximum tolerated dose recommended phase 2 dose of Clofarabine in combination with Etoposide and Mitoxantrone for therapy of relapsed or refractory acute leukemias. The investigators will observe responses with these therapy agents and assess the impact of Clofarabine interacting with Etoposide in induction of DNA strand breaks.
Detailed description
This will be a phase I study with a standard 3x3 design. Patients will proceed to treatment through a series of cohorts with the three drugs being delivered over five days beginning with a dose of Etoposide 100 mg/m2 on days 1-5,Mitoxantrone 8 mg/m2 days 1-3, and clofarabine at 20 mg/m2 IV on days 2-6. Presuming this and subsequent cohorts are tolerable and no more than 1 patient per cohort develops DLT, MTD patients will be treated in cohorts of 3-6 patients up to a final dose level of Etoposide 100 mg/m2 on days 1-5,Mitoxantrone 8 mg/m2 days 1-5, and Clofarabine at 30 mg/m2 IV on days 2-6. Patients failing to enter remission may receive 4 days of therapy with Etoposide 100 mg/m2 on days 1-4,Mitoxantrone 8 mg/m2 days 1-2 or 1-4,and Clofarabine at 20-30 mg/m2 IV on days 1-4. According to established definitions for dose limiting toxicity a recommended phase II dose will be established. After this is established the final cohort will be expanded to 15 patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Treatment Cohort 1 | Experimental | Drug: Clofarabine, Drug: Mitoxantrone, Drug: EtoposideEtoposide (Days 1-5) 100 mg/m2; Mitoxantrone (Days 1-3) 8 mg/m2 (3 doses); Clofarabine (Days 2-6) 20 mg/m2 |
| Treatment Cohort 2 | Experimental | Drug: Clofarabine, Drug: Mitoxantrone, Drug: EtoposideEtoposide (Days 1-5) 100 mg/m2; Mitoxantrone (Days 1-3) 8 mg/m2; Clofarabine (Days 2-6) 25 mg/m2 |
| Treatment Cohort 3 | Experimental | Drug: Clofarabine, Drug: Mitoxantrone, Drug: EtoposideEtoposide (Days 1-5) 100 mg/m2; Mitoxantrone (Days 1-3) 8 mg/m2; Clofarabine (Days 2-6) 30 mg/m2 |
| Treatment Cohort 4 | Experimental | Drug: Clofarabine, Drug: Mitoxantrone, Drug: EtoposideEtoposide (Days 1-5) 100 mg/m2; Mitoxantrone (Days 1-5) 8 mg/m2; Clofarabine (Days 2-6) 30 mg/m2 |
| Treatment Cohort 0 | Experimental | Drug: Clofarabine, Drug: Mitoxantrone, Drug: EtoposideEtoposide (Days 1-5) 100 mg/m2; Mitoxantrone (Days 1-3) 8 mg/m2; Clofarabine (Days 2-6) 10 mg/m2 (In the event of a DLT in Treatment Cohort 1) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adequate renal and hepatic function.
- Capable of understanding the investigational nature, potential risks and benefits of the study and able to provide valid informed consent.
- Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment.
- Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.
- LVEF must be ≥ 50% within 2 weeks.
Key exclusion criteria (6 listed)
- Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.
- Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea. The patient must have recovered from all acute toxicities from any previous therapy.
- Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver or other organ system that may place the patient at undue risk to undergo treatment.
- Patients with a systemic fungal, bacterial, viral, or other infection not controlled.
- Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow-up or interpretation of study results.
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 |
|---|---|---|
| ClofarabineAlso: ClolarFor Treatment Clofarabine will be administered on Days 2-6 at the dose of 20mg/m2 in Cohort 1, 25mg/m2 in Cohort 2 and 30mg/m2 in Cohort 3 and 4 and 10mg/m2 in Cohort 0 (In the event of excessive DLT in Treatment Cohort 1). For Retreatment Clofarabine will be administered on Days 1-4 at the dose of 20mg/m2 in Cohort 1, 25mg/m2 in Cohort 2 and 30mg/m2 in Cohort 3 and 4 and 10mg/m2 in Cohort 0 (In the event of excessive DLT in Retreatment Cohort 1). | Drug | Treatment Cohort 0, Treatment Cohort 1, Treatment Cohort 2, Treatment Cohort 3, Treatment Cohort 4 |
| MitoxantroneAlso: Mitoxantrone hydrochlorideFor Treatment Mitoxantrone will be administered on Days 1-3 at the dose of 8mg/m2 in Cohort 1, 2, 3 and on Days 1-5 for Cohort 4 and on Days 1-3 8mg/m2 in Cohort 0 (In the event of excessive DLT in Treatment Cohort 1). For Retreatment Mitoxantrone will be administered on Days 1-2 (2 doses) at the dose of 8mg/m2 in Cohort 1, 2 and 3 and on Days 1-4 (4 doses) at the dose of 8mg/m2 in Cohort 4, and on Days 1-2 (2 doses) at the dose of 8mg/m2 in Cohort 0 (In the event of excessive DLT in Retreatment Cohort 1). | Drug | Treatment Cohort 0, Treatment Cohort 1, Treatment Cohort 2, Treatment Cohort 3, Treatment Cohort 4 |
| EtoposideAlso: Etoposide PhosphateFor Treatment Etoposide will be administered on Days 1-5 at the dose of 100mg/m2 in Cohort 1, 2, 3, 4 and Cohort 0 (in the event of excessive DLT in Treatment Cohort 1). For Retreatment Etoposide will be administered on Days 1-4 at the dose of 100mg/m2 in Cohort 1, 2, 3, 4 and Cohort 0 (in the event of excessive DLT in Retreatment Cohort 1). | Drug | Treatment Cohort 0, Treatment Cohort 1, Treatment Cohort 2, Treatment Cohort 3, Treatment Cohort 4 |
Primary outcome
Establish toxicity of Clofarabine in combination with Etoposide and Mitoxantrone for therapy of relapsed or refractory acute leukemias
Time frame: Days 30-45
Establish dose limiting toxicity of Clofarabine in combination with Etoposide and Mitoxantrone for therapy of relapsed or refractory acute leukemias
Time frame: Days 30-45
Establish maximum tolerated dose recommend Phase 2 dose of Clofarabine in combination with Etoposide and Mitoxantrone for therapy of relapsed or refractory acute leukemias
Time frame: Days 30-45
2 secondary outcomes
Observe response of relapsed or refractory acute leukemias to therapy with these agents.
Time frame: 30-70 days
Assess the impact of Clofarabine interacting with Etoposide and Mitoxantrone in induction of DNA strand breaks
Time frame: 30-45 days
Results and safety
The study was stopped early (reason given: study closed prematurely). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2019.
- Individual participant dataSharing planned: No. Determine if data is valuable
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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.
David F. Claxton, MD principal investigator
Penn State College of Medicine
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 Clofarabine, Mitoxantrone and Etoposide in people with Leukemia, run by Milton S. Hershey Medical Center 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 5 inclusion and 6 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: stopped early, as of the sponsor's last update on 24 Jul 2019. 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 was stopped early (reason given: study closed prematurely). Results are not available in the source record.
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?
Establish toxicity of Clofarabine in combination with Etoposide and Mitoxantrone for therapy of relapsed or refractory acute leukemias (time frame: Days 30-45). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Jul 2019.