Acute Myeloid LeukemiaPhase 1/2NCT00583102
Dose Escalation Phase I/II Study of Lovastatin With High-Dose Cytarabine for Refractory or Relapsed AML
A Phase 1/2 study testing Cytarabine and Lovastatin in people with Acute Myeloid Leukemia, run by University of Iowa at 1 site in United States.
Trial summary
The purpose of this study is to test the safety and effectiveness of combining a drug known as Lovastatin to the chemotherapy drug cytarabine. Lovastatin is currently used to lower blood cholesterol levels and lab data suggests that it increases the anti-leukemia activity of cytarabine. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- Cytarabine and Lovastatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2001to Jun 2013
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with primary refractory AML (that is no prior remission). Patients who have greater than 10% AML blasts in the bone marrow or blood upon recovery from two cycles of standard cytarabine- and anthracycline-based induction chemotherapy are eligible. Patients who have received etoposide and/or 6-thioguanine during remission induction will be eligible.
- Patients with relapsed AML. Patients must have had a documented remission lasting > 30 days at some point during their prior therapy. Their current relapse must be untreated. Relapse is defined as the presence of greater than 10% AML blasts in the bone marrow or blood after having had a documented remission.
- Patients who have received a high-dose cytarabine containing regimen (>2 g/m2/dose) within 3 months prior to registration on this protocol are not eligible.
- No active CNS involvement. A lumbar puncture prior to treatment is not required and should not be performed in the absence of significant CNS symptoms or signs.
- Non-pregnant and non-nursing. Treatment under this protocol would expose an unborn child to significant risks. Women and men of reproductive potential should agree to use an effective means of birth control.
Who cannot join
- Although NOT considered formal Exclusion Criteria, study physicians are strongly encouraged as part of this decision-making process to recognize that the following may increase the risks to a subject entering this protocol:
- Other serious illnesses which would limit survival to <2 years, or a psychiatric condition which would prevent compliance with treatment or informed consent.
- Performance Status > 2.
- Uncontrolled or severe cardiovascular disease, diabetes, pulmonary disease, or infection, which in the opinion of the treating physician, would make this protocol treatment unreasonably hazardous for the patient.
- Patients with a "currently active" second malignancy other than non-melanoma skin cancers. Patients are not considered to have a "currently active" malignancy if they have completed therapy and considered by their physician to be at less than 30% risk of relapse within one year.
- Patients who have received any investigational agent within the prior 4 weeks.
Trial locations and contacts
1 site in 1 country.
United States1 site
Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
About this study
Official title: A Dose Escalation Phase I/II Study of Lovastatin With High-Dose Cytarabine for Patients With Refractory or Relapsed Acute Myeloid Leukemia
The purpose of this study is to test the safety and effectiveness of combining a drug known as Lovastatin to the chemotherapy drug cytarabine. Lovastatin is currently used to lower blood cholesterol levels and lab data suggests that it increases the anti-leukemia activity of cytarabine. This research is being done because high doses of cytarabine induce remissions in only about 25% of patients with acute myeloid leukemia.
Read the detailed description
The rationale for combining lovastatin with cytosine arabinoside (HiDAC) in this trial is based on a study in press in Leukemia Research. This study demonstrated that there are synergistic interactions between cytosine arabinoside and lovastatin against human leukemia cell lines. In particular, this synergistic activity was observed in MTT assay. Given that there is such synergistic interaction in vitro it is reasonable to determine whether such interaction occurs in vivo. The proposed trial thus uses standard doses of HiDAC with incrementally increasing dose of lovastatin. This particular trial will follow an accelerated titration for lovastatin. The first dose level will be lovastatin at 0.5 mg/kg/day, divided into two daily PO doses given Q 12 hours on Days 1 -7 for a total of 14 doses. Doses should be rounded to the nearest 20 mg. After each subject reaches day 14, subsequent subjects will be treated at incrementally increasing doses that are 1 mg/kg/day, 2 mg/kg/day, 4 mg/kg/day, 8 mg/kg/day, 12 mg/kg/day, 18 mg/kg/day, and 24 mg/kg/day, with all doses divided into two daily PO doses given Q 12 hours on Days 1 - 7 for a total of 14. If MTD is not reached at the 24 mg/kg/day dose level, further dose escalations will occur with a 33% increase in dose at each level, rounded to the nearest 20 mg/kg/day.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- Cytarabine, Lovastatin
- Keywords
- Acute Myeloid Leukemia, AML, Lovastatin, Cytarabine
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CytarabineDrug
Also called CYTOSAR-U, Depocyt
Cytarabine dosage: 3.0 g/m2 IV over 3 hours every 12 hours on days 3-7.
LovastatinDrug
Also called Mevacor, Altoprev
Lovastatin dosage: The first dose level will be lovastatin at 0.5 mg/kg/day. After each patient reaches day 14 subsequent patients will be treated at incrementally increasing doses that are 1 mg/kg/day, 2 mg/kg/day, 4 mg/kg/day, 8 mg/kg/day, 12 mg/kg/day, 18 mg/kg/day, and 24 mg/kg/day. If MTD is not reached at this dose of 24 mg/kg/day further dose escalations will occur with a 33% increase in dose at each level rounded to the nearest mg/kg/day.
| Study group | Role | What they receive |
|---|---|---|
| Lovastatin followed by Cytarabine | Experimental | The subject will receive high dose cytarabine as well as lovastatin. The subject will take doses of lovastatin twice a day, about 12 hours apart. On the third day, the subject will begin high-dose cytarabine IV over 3 hours, twice a day, starting 1 hour after the lovastatin dose for 5 days. Receives: Drug: Cytarabine; Drug: Lovastatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Remission Rate
The primary study end point will be complete remission rate.
Complete Remission (CR):
Complete remission is defined as the presence of all of the following:
Peripheral Blood Counts (sustained > 30 days)
- Absolute neutrophil count ³1500/ml.
- Platelet count ³100,000/ml.
- No leukemic blasts in the peripheral blood.
- Transfusion independent for red cells and platelets. Bone Marrow
- Cellularity >20% with maturation of all cell lines.
- No Auer rods.
- <5% blast cells. No extramedullary leukemia (such as CNS or soft tissue involvement). OR Complete Response with Incomplete Platelet Recovery (CRp): CRp satisfies all CR criteria except platelets < 100,000/µL.
Partial Remission (PR):
Must meet all criteria of a CR except that the bone marrow may contain 5-24% blasts.
Treatment Failure:
Failure to achieve a CR.
Measured: 5 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Dec 2007 (estimated)
- Study startJun 2001
- Primary completionFeb 2013
- Study completionJun 2013
Why it stopped: Slow accrual, PI left institution
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by University of IowaThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Iowa
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Raymond J Hohl, University of Iowa
- Investigators
- Raymond Hohl, MD, Principal investigator, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00583102
- Sponsor's protocol ID
- 200104050
- Status last verified
- Dec 2017
- First submitted
- 20 Dec 2007
- Last updated
- 5 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Dose Escalation Phase I/II Study of Lovastatin With High-Dose Cytarabine for Patients With Refractory or Relapsed Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT00583102
- Acronym / sponsor ID
- 200104050
- Conditions
- Acute Myeloid Leukemia
- Keywords
- Acute Myeloid Leukemia, AML, Lovastatin, Cytarabine
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual, PI left institution
- Enrolment
- 23 participants (actual)
- Lead sponsor
- University of IowaUniversity, hospital or other
- Study start
- Jun 2001 (actual)
- Primary completion
- Feb 2013 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 31 Dec 2007 (estimated)
- Results
- Posted 5 Jan 2018
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 test the safety and effectiveness of combining a drug known as Lovastatin to the chemotherapy drug cytarabine. Lovastatin is currently used to lower blood cholesterol levels and lab data suggests that it increases the anti-leukemia activity of cytarabine. This research is being done because high doses of cytarabine induce remissions in only about 25% of patients with acute myeloid leukemia.
Detailed description
The rationale for combining lovastatin with cytosine arabinoside (HiDAC) in this trial is based on a study in press in Leukemia Research. This study demonstrated that there are synergistic interactions between cytosine arabinoside and lovastatin against human leukemia cell lines. In particular, this synergistic activity was observed in MTT assay. Given that there is such synergistic interaction in vitro it is reasonable to determine whether such interaction occurs in vivo. The proposed trial thus uses standard doses of HiDAC with incrementally increasing dose of lovastatin. This particular trial will follow an accelerated titration for lovastatin. The first dose level will be lovastatin at 0.5 mg/kg/day, divided into two daily PO doses given Q 12 hours on Days 1 -7 for a total of 14 doses. Doses should be rounded to the nearest 20 mg. After each subject reaches day 14, subsequent subjects will be treated at incrementally increasing doses that are 1 mg/kg/day, 2 mg/kg/day, 4 mg/kg/day, 8 mg/kg/day, 12 mg/kg/day, 18 mg/kg/day, and 24 mg/kg/day, with all doses divided into two daily PO doses given Q 12 hours on Days 1 - 7 for a total of 14. If MTD is not reached at the 24 mg/kg/day dose level, further dose escalations will occur with a 33% increase in dose at each level, rounded to the nearest 20 mg/kg/day.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lovastatin followed by Cytarabine | Experimental | Drug: Cytarabine, Drug: LovastatinThe subject will receive high dose cytarabine as well as lovastatin. The subject will take doses of lovastatin twice a day, about 12 hours apart. On the third day, the subject will begin high-dose cytarabine IV over 3 hours, twice a day, starting 1 hour after the lovastatin dose for 5 days. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients with primary refractory AML (that is no prior remission). Patients who have greater than 10% AML blasts in the bone marrow or blood upon recovery from two cycles of standard cytarabine- and anthracycline-based induction chemotherapy are eligible. Patients who have received etoposide and/or 6-thioguanine during remission induction will be eligible.
- Patients with relapsed AML. Patients must have had a documented remission lasting > 30 days at some point during their prior therapy. Their current relapse must be untreated. Relapse is defined as the presence of greater than 10% AML blasts in the bone marrow or blood after having had a documented remission.
- Patients who have received a high-dose cytarabine containing regimen (>2 g/m2/dose) within 3 months prior to registration on this protocol are not eligible.
- No active CNS involvement. A lumbar puncture prior to treatment is not required and should not be performed in the absence of significant CNS symptoms or signs.
- Non-pregnant and non-nursing. Treatment under this protocol would expose an unborn child to significant risks. Women and men of reproductive potential should agree to use an effective means of birth control.
Key exclusion criteria (6 listed)
- Although NOT considered formal Exclusion Criteria, study physicians are strongly encouraged as part of this decision-making process to recognize that the following may increase the risks to a subject entering this protocol:
- Other serious illnesses which would limit survival to <2 years, or a psychiatric condition which would prevent compliance with treatment or informed consent.
- Performance Status > 2.
- Uncontrolled or severe cardiovascular disease, diabetes, pulmonary disease, or infection, which in the opinion of the treating physician, would make this protocol treatment unreasonably hazardous for the patient.
- Patients with a "currently active" second malignancy other than non-melanoma skin cancers. Patients are not considered to have a "currently active" malignancy if they have completed therapy and considered by their physician to be at less than 30% risk of relapse within one year.
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 |
|---|---|---|
| CytarabineAlso: CYTOSAR-U, DepocytCytarabine dosage: 3.0 g/m2 IV over 3 hours every 12 hours on days 3-7. | Drug | Lovastatin followed by Cytarabine |
| LovastatinAlso: Mevacor, AltoprevLovastatin dosage: The first dose level will be lovastatin at 0.5 mg/kg/day. After each patient reaches day 14 subsequent patients will be treated at incrementally increasing doses that are 1 mg/kg/day, 2 mg/kg/day, 4 mg/kg/day, 8 mg/kg/day, 12 mg/kg/day, 18 mg/kg/day, and 24 mg/kg/day. If MTD is not reached at this dose of 24 mg/kg/day further dose escalations will occur with a 33% increase in dose at each level rounded to the nearest mg/kg/day. | Drug | Lovastatin followed by Cytarabine |
Primary outcome
Complete Remission Rate
Time frame: 5 weeks
The primary study end point will be complete remission rate. Complete Remission (CR): Complete remission is defined as the presence of all of the following: Peripheral Blood Counts (sustained > 30 days) * Absolute neutrophil count ³1500/ml. * Platelet count ³100,000/ml. * No leukemic blasts in the peripheral blood. * Transfusion independent for red cells and platelets. Bone Marrow * Cellularity >20% with maturation of all cell lines. * No Auer rods. * <5% blast cells. No extramedullary leukemia (such as CNS or soft tissue involvement). OR Complete Response with Incomplete Platelet Recovery (CRp): CRp satisfies all CR criteria except platelets < 100,000/µL. Partial Remission (PR): Must meet all criteria of a CR except that the bone marrow may contain 5-24% blasts. Treatment Failure: Failure to achieve a CR.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Raymond Hohl, MD principal investigator
University of Iowa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Cytarabine and Lovastatin in people with Acute Myeloid Leukemia, run by University of Iowa 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 5 Jan 2018. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Jan 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Complete Remission Rate (time frame: 5 weeks). 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 5 Jan 2018.