Acute Myeloid LeukemiaPhase 1NCT03318016
Arsenic Trioxide With Cyclophosphamide in Patients With Relapsed/Refractory Acute Myeloid Leukemia
A Phase 1 study testing Cyclophosphamide 500 MG, Cyclophosphamide 1000 MG and Cyclophosphamide 2000 MG in people with Acute Myeloid Leukemia and Relapsed/Refractory Acute Myeloid Leukemia, run by University of Colorado, Denver at 1 site in United States.
Trial summary
Determine the maximum tolerated dose (MTD) and toxicity profile of the combination of cyclophosphamide and ATO (Arsenic Trioxide) in subjects with relapsed refractory AML. Determine the efficacy of ATO and cyclophosphamide in this population, as defined by response rate, response duration, event-free survival (EFS)… Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Acute Myeloid Leukemia, Relapsed/Refractory Acute Myeloid Leukemia
- What is being tested?
- Cyclophosphamide 500 MG, Cyclophosphamide 1000 MG and Cyclophosphamide 2000 MG
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Dec 2017to 20 Jan 2021
- Phase
- Phase 1
- 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
- WHO-confirmed AML, other than APL, with no standard treatment options available
- Age 18 years or older
- Relapsed or refractory (resistant) disease, as defined by standard criteria
- Relapsed: Bone marrow blasts ≥5%, reappearance of blasts in the blood, or development of extramedullary disease following achievement of CR/CRi/CRp/MLFS
- Refractory (resistant): Failure to achieve CR/CRi/MLFS in subjects who survive ≥7 days following completion of initial treatment, with evidence of persistent leukemia by blood and/or bone marrow examination
- >14 days since any prior therapy for AML excluding hydroxyurea
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- Willing and able to understand and voluntarily sign a written informed consent
- Able to adhere to the study visit schedule and other protocol requirements
- Women of childbearing potential must use an acceptable form of birth control for 28 days prior to beginning study treatment, through the duration of study treatment, and for 3 months after discontinuing study treatment.
Who cannot join
- New York Heart Association Class III or IV heart failure
- Unstable angina pectoris
- Significant uncontrolled cardiac arrhythmias, including ventricular arrhythmias, congenital long QT syndrome, symptomatic atrial fibrillation, symptomatic bradycardia, right bundle branch block plus left anterior hemiblock or bifasicular block
- QTc >500 ms, uncorrectable by managing electrolytes and medications, using the QTcF formula in Appendix D.
- Active acute graft vs. host disease ≥ grade 2 or active extensive chronic GVHD
- Relapse after allogeneic stem cell transplantation prior to post-transplant day 30
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- Active central nervous system (CNS) involvement of leukemia (lumbar puncture not required to rule out CNS involvement if not suspected)
- Uncontrolled psychiatric illness that would limit compliance with requirements
- Pregnant or breast feeding females
- Laboratory abnormalities:
- Either creatinine >2.0 mg/dL or creatinine clearance <30 mL/min
- Total bilirubin > 3 x institutional upper limit of normal (ULN) (unless documented Gilbert's syndrome)
- AST or ALT > 3 x institutional ULN, unless felt to be due to disease involvement
- Other medical or psychiatric illness or organ dysfunction or laboratory abnormality which, in the opinion of the investigator, would compromise the subject's safety or interfere with data interpretation.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Denver
Aurora, Colorado, 80045
About this study
Official title: Phase I Trial of Arsenic Trioxide With Cyclophosphamide in Patients With Relapsed/Refractory Acute Myeloid Leukemia
Determine the maximum tolerated dose (MTD) and toxicity profile of the combination of cyclophosphamide and ATO (Arsenic Trioxide) in subjects with relapsed refractory AML.
Determine the efficacy of ATO and cyclophosphamide in this population, as defined by response rate, response duration, event-free survival (EFS) and overall survival (OS).
Determine the number of transplant-eligible subjects who are successfully bridged to stem cell transplantation or donor lymphocyte infusion.
Read the detailed description
This is an open label phase 1 study of fixed dose ATO (Arsenic Trioxide) and escalating doses of cyclophosphamide using a standard 3+3 dose escalation design. All subjects will be treated with sequential cycles of 3 days of ATO at 0.15 mg/kg/d IV followed by Cyclophosphamide as a single IV dose on day 4 along with mesna at a dose equal to the cyclophosphamide (for doses ≥1000 mg/m2) and hydration for a maximum of 6 cycles. ATO and Cyclophosphamide will be repeated every 28-42 days. Treatment will be given inpatient for the first cycle, with the option of outpatient treatment for subsequent cycles. Subjects may remain on study in the absence of disease progression or unacceptable toxicity for a maximum six cycles. Toxicity assessments will be performed continuously; DLT determination will be made based on adverse events (AEs) that occur during cycle 1 (day 1-28). An expansion cohort of ten subjects at the maximum tolerated dose will occur at the conclusion of dose escalation.
- Being tested
- Cyclophosphamide 500 MG, Cyclophosphamide 1000 MG, Cyclophosphamide 2000 MG, Cyclophosphamide 3000 MG, Cyclophosphamide 4000 MG
- Keywords
- Arsenic Trioxide, Cyclophosphamide
- 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.
Cyclophosphamide 500 MGDrug
Also called cytophosphane
ATO at a fixed dose of 0.15 mg/kg/d IV followed by Cyclophosphamide 500 mg/m2 on day 4 as a single IV dose along with hydration for a maximum of 6 doses
Cyclophosphamide 1000 MGDrug
Also called cytophosphane
Enrolled subjects will receive 3 consecutive days of ATO at a fixed dose of 0.15 mg/kg/d IV followed by Cyclophosphamide 1000 mg/m2on day 4 as a single IV dose along with Mesna (in subjects receiving ≥1000mg/m2 Cy) and hydration for a maximum of 6 doses
Cyclophosphamide 2000 MGDrug
Also called cytophosphane
Enrolled subjects will receive 3 consecutive days of ATO at a fixed dose of 0.15 mg/kg/d IV followed by Cyclophosphamide 2000 mg/m2on day 4 as a single IV dose along with Mesna (in subjects receiving ≥1000mg/m2 Cy) and hydration for a maximum of 6 doses
Cyclophosphamide 3000 MGDrug
Also called cytophosphane
Enrolled subjects will receive 3 consecutive days of ATO at a fixed dose of 0.15 mg/kg/d IV followed by Cyclophosphamide 3000 mg/m2on day 4 as a single IV dose along with Mesna (in subjects receiving ≥1000mg/m2 Cy) and hydration for a maximum of 6 doses
Cyclophosphamide 4000 MGDrug
Also called cytophosphane
Enrolled subjects will receive 3 consecutive days of ATO at a fixed dose of 0.15 mg/kg/d IV followed by Cyclophosphamide 4000 mg/m2on day 4 as a single IV dose along with Mesna (in subjects receiving ≥1000mg/m2 Cy) and hydration for a maximum of 6 doses
| Study group | Role | What they receive |
|---|---|---|
| Cohort -1 | Experimental | 3 consecutive days of ATO at a fixed dose of 0.15 mg/kg/d IV followed by Cyclophosphamide on day 4 as a single IV Receives: Drug: Cyclophosphamide 500 MG |
| Cohort 1 | Experimental | 3 consecutive days of ATO at a fixed dose of 0.15 mg/kg/d IV followed by Cyclophosphamide on day 4 as a single IV Receives: Drug: Cyclophosphamide 1000 MG |
| Cohort 2 | Experimental | 3 consecutive days of ATO at a fixed dose of 0.15 mg/kg/d IV followed by Cyclophosphamide on day 4 as a single IV Receives: Drug: Cyclophosphamide 2000 MG |
| Cohort 3 | Experimental | 3 consecutive days of ATO at a fixed dose of 0.15 mg/kg/d IV followed by Cyclophosphamide on day 4 as a single IV Receives: Drug: Cyclophosphamide 3000 MG |
| Cohort 4 | Experimental | 3 consecutive days of ATO at a fixed dose of 0.15 mg/kg/d IV followed by Cyclophosphamide on day 4 as a single IV Receives: Drug: Cyclophosphamide 4000 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants That Reached Maximally Tolerated Dose (MTD) of Cyclophosphamide and ATO
Number of Participants that were treated in each Cohort in attempt to establish Maximally Tolerated Dose (MTD) of cyclophosphamide with ATO is defined as the highest dose level of 1000 mg/m2. MTD is established when at least 6 participants within a Cohort have responded without toxicity.
The trial is organized in a standard, phase I, 3+3 design. The first 3 subjects will be assigned to cohort 1. Per standard trial design, if there are 0/3 dose-limiting toxicities (DLT) in this cohort, the next three subjects will be assigned to cohort 2. This will continue until MTD is established.
Measured: 26 months
Secondary outcomes (1)
Overall Response Rate (ORR) Using ATO and Cyclophosphamide
ORR defined by complete remission/complete remission with incomplete recovery of blood counts (CR/CRi), morphologic leukemia free state (MLFS) and partial responses (PR)
Measured: 26 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2017
- Study start15 Dec 2017
- Primary completion15 Jan 2020
- Study completion20 Jan 2021
Why it stopped: Low enrollment, University Scientific Review Committee required study closure.
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 Colorado, DenverThe 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
- Sequential
- Model description
- * Cohort -1 (3-6 subjects, if needed): Cyclophosphamide 500 mg/m2 * Cohort 1 (3-6 subjects): Cyclophosphamide 1000 mg/m2 * Cohort 2 (3-6 subjects): Cyclophosphamide 2000 mg/m2 * Cohort 3 (3-6 subjects): Cyclophosphamide 3000 mg/m2 * Cohort 4 (3 subjects): Cyclophosphamide 4000 mg/m2 ATO and Cyclophosphamide will be repeated every 28 days.
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Daniel Pollyea, MD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03318016
- Sponsor's protocol ID
- 17-0754.cc
- Other IDs
- NCI-2017-02403
- Status last verified
- Feb 2024
- First submitted
- 18 Oct 2017
- Last updated
- 1 Aug 2024
- 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 1 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of Arsenic Trioxide With Cyclophosphamide in Patients With Relapsed/Refractory Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT03318016
- Acronym / sponsor ID
- 17-0754.cc
- Keywords
- Arsenic Trioxide, Cyclophosphamide
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low enrollment, University Scientific Review Committee required study closure.
- Enrolment
- 5 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Study start
- 15 Dec 2017 (actual)
- Primary completion
- 15 Jan 2020 (actual)
- Study completion
- 20 Jan 2021 (actual)
- First posted
- 23 Oct 2017 (actual)
- Results
- Posted 1 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Determine the maximum tolerated dose (MTD) and toxicity profile of the combination of cyclophosphamide and ATO (Arsenic Trioxide) in subjects with relapsed refractory AML.
Determine the efficacy of ATO and cyclophosphamide in this population, as defined by response rate, response duration, event-free survival (EFS) and overall survival (OS).
Determine the number of transplant-eligible subjects who are successfully bridged to stem cell transplantation or donor lymphocyte infusion.
Detailed description
This is an open label phase 1 study of fixed dose ATO (Arsenic Trioxide) and escalating doses of cyclophosphamide using a standard 3+3 dose escalation design. All subjects will be treated with sequential cycles of 3 days of ATO at 0.15 mg/kg/d IV followed by Cyclophosphamide as a single IV dose on day 4 along with mesna at a dose equal to the cyclophosphamide (for doses ≥1000 mg/m2) and hydration for a maximum of 6 cycles. ATO and Cyclophosphamide will be repeated every 28-42 days. Treatment will be given inpatient for the first cycle, with the option of outpatient treatment for subsequent cycles. Subjects may remain on study in the absence of disease progression or unacceptable toxicity for a maximum six cycles. Toxicity assessments will be performed continuously; DLT determination will be made based on adverse events (AEs) that occur during cycle 1 (day 1-28). An expansion cohort of ten subjects at the maximum tolerated dose will occur at the conclusion of dose escalation.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
- Model description
- * Cohort -1 (3-6 subjects, if needed): Cyclophosphamide 500 mg/m2 * Cohort 1 (3-6 subjects): Cyclophosphamide 1000 mg/m2 * Cohort 2 (3-6 subjects): Cyclophosphamide 2000 mg/m2 * Cohort 3 (3-6 subjects): Cyclophosphamide 3000 mg/m2 * Cohort 4 (3 subjects): Cyclophosphamide 4000 mg/m2 ATO and Cyclophosphamide will be repeated every 28 days.
| Arm | Type | Receives |
|---|---|---|
| Cohort -1 | Experimental | Drug: Cyclophosphamide 500 MG3 consecutive days of ATO at a fixed dose of 0.15 mg/kg/d IV followed by Cyclophosphamide on day 4 as a single IV |
| Cohort 1 | Experimental | Drug: Cyclophosphamide 1000 MG3 consecutive days of ATO at a fixed dose of 0.15 mg/kg/d IV followed by Cyclophosphamide on day 4 as a single IV |
| Cohort 2 | Experimental | Drug: Cyclophosphamide 2000 MG3 consecutive days of ATO at a fixed dose of 0.15 mg/kg/d IV followed by Cyclophosphamide on day 4 as a single IV |
| Cohort 3 | Experimental | Drug: Cyclophosphamide 3000 MG3 consecutive days of ATO at a fixed dose of 0.15 mg/kg/d IV followed by Cyclophosphamide on day 4 as a single IV |
| Cohort 4 | Experimental | Drug: Cyclophosphamide 4000 MG3 consecutive days of ATO at a fixed dose of 0.15 mg/kg/d IV followed by Cyclophosphamide on day 4 as a single IV |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- WHO-confirmed AML, other than APL, with no standard treatment options available
- Age 18 years or older
- Relapsed or refractory (resistant) disease, as defined by standard criteria
- >14 days since any prior therapy for AML excluding hydroxyurea
- Willing and able to understand and voluntarily sign a written informed consent
Key exclusion criteria (14 listed)
- New York Heart Association Class III or IV heart failure
- Unstable angina pectoris
- Significant uncontrolled cardiac arrhythmias, including ventricular arrhythmias, congenital long QT syndrome, symptomatic atrial fibrillation, symptomatic bradycardia, right bundle branch block plus left anterior hemiblock or bifasicular block
- QTc >500 ms, uncorrectable by managing electrolytes and medications, using the QTcF formula in Appendix D.
- Active acute graft vs. host disease ≥ grade 2 or active extensive chronic GVHD
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 |
|---|---|---|
| Cyclophosphamide 500 MGAlso: cytophosphaneATO at a fixed dose of 0.15 mg/kg/d IV followed by Cyclophosphamide 500 mg/m2 on day 4 as a single IV dose along with hydration for a maximum of 6 doses | Drug | Cohort -1 |
| Cyclophosphamide 1000 MGAlso: cytophosphaneEnrolled subjects will receive 3 consecutive days of ATO at a fixed dose of 0.15 mg/kg/d IV followed by Cyclophosphamide 1000 mg/m2on day 4 as a single IV dose along with Mesna (in subjects receiving ≥1000mg/m2 Cy) and hydration for a maximum of 6 doses | Drug | Cohort 1 |
| Cyclophosphamide 2000 MGAlso: cytophosphaneEnrolled subjects will receive 3 consecutive days of ATO at a fixed dose of 0.15 mg/kg/d IV followed by Cyclophosphamide 2000 mg/m2on day 4 as a single IV dose along with Mesna (in subjects receiving ≥1000mg/m2 Cy) and hydration for a maximum of 6 doses | Drug | Cohort 2 |
| Cyclophosphamide 3000 MGAlso: cytophosphaneEnrolled subjects will receive 3 consecutive days of ATO at a fixed dose of 0.15 mg/kg/d IV followed by Cyclophosphamide 3000 mg/m2on day 4 as a single IV dose along with Mesna (in subjects receiving ≥1000mg/m2 Cy) and hydration for a maximum of 6 doses | Drug | Cohort 3 |
| Cyclophosphamide 4000 MGAlso: cytophosphaneEnrolled subjects will receive 3 consecutive days of ATO at a fixed dose of 0.15 mg/kg/d IV followed by Cyclophosphamide 4000 mg/m2on day 4 as a single IV dose along with Mesna (in subjects receiving ≥1000mg/m2 Cy) and hydration for a maximum of 6 doses | Drug | Cohort 4 |
Primary outcome
Number of Participants That Reached Maximally Tolerated Dose (MTD) of Cyclophosphamide and ATO
Time frame: 26 months
Number of Participants that were treated in each Cohort in attempt to establish Maximally Tolerated Dose (MTD) of cyclophosphamide with ATO is defined as the highest dose level of 1000 mg/m2. MTD is established when at least 6 participants within a Cohort have responded without toxicity. The trial is organized in a standard, phase I, 3+3 design. The first 3 subjects will be assigned to cohort 1. Per standard trial design, if there are 0/3 dose-limiting toxicities (DLT) in this cohort, the next three subjects will be assigned to cohort 2. This will continue until MTD is established.
1 secondary outcome
Overall Response Rate (ORR) Using ATO and Cyclophosphamide
Time frame: 26 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2024.
- 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.
Daniel Pollyea, MD principal investigator
University of Colorado, Denver
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 Cyclophosphamide 500 MG, Cyclophosphamide 1000 MG and Cyclophosphamide 2000 MG in people with Acute Myeloid Leukemia and Relapsed/Refractory Acute Myeloid Leukemia, run by University of Colorado, Denver 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 9 inclusion and 14 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 1 Aug 2024. 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?
Yes. Results are posted in the registry (first posted 1 Aug 2024). 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?
Number of Participants That Reached Maximally Tolerated Dose (MTD) of Cyclophosphamide and ATO (time frame: 26 months). 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 1 Aug 2024; AzTrials last refreshed its copy on 26 Oct 2026.