A Phase 1 interventional study of Cyclophosphamide 500 MG and Cyclophosphamide 1000 MG in Acute Myeloid Leukemia and Relapsed/Refractory Acute Myeloid Leukemia, sponsored by University of Colorado, Denver. Terminated at 1 site in United States. Open to participants aged 18 Years to 99 Years. Per ClinicalTrials.gov, last updated 2024-08-01.
Sponsored by University of Colorado, Denver · Phase 1, Interventional, and Treatment
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.
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.
3,667 studies on the registry are indexed under Leukemia, Myeloid, Acute; 816 are open to participants now.
This study's enrollment of 5 is below the median of 40 across 3,005 interventional studies indexed under Leukemia, Myeloid, Acute.
Browse Leukemia, Myeloid, Acute studies →University of Colorado, Denver is the lead sponsor of 1,543 studies on the registry; 317 are open to participants now.
Of its 147 completed or terminated interventional studies of FDA-regulated products, 92 (63%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
(resistant) disease, as defined by standard criteria
Exclusion Criteria:
Laboratory abnormalities:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
After a transplant from a donor, the donor’s immune cells attack the recipient’s body, often the skin, gut or liver.
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GVHD (graft-versus-host disease)
After a transplant from a donor, the donor’s immune cells attack the recipient’s body, often the skin, gut or liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Allogeneic and autologous transplant
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
Drug: Cyclophosphamide 500 MG
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
Drug: Cyclophosphamide 1000 MG
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
Drug: Cyclophosphamide 2000 MG
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
Drug: Cyclophosphamide 3000 MG
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
Drug: Cyclophosphamide 4000 MG
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
Also known as: 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
Also known as: 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
Also known as: 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
Also known as: 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
Also known as: cytophosphane
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.
Time frame: 26 months
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)
Time frame: 26 months
| Milestone | Cohort -1 | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 |
|---|---|---|---|---|---|
| Started | 0 | 3 | 2 | 0 | 0 |
| Completed | 0 | 3 | 2 | 0 | 0 |
| Not completed | 0 | 0 | 0 | 0 | 0 |
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.
| Participants | Cohort -1 | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 |
|---|---|---|---|---|---|
| Number of Participants That Reached Maximally Tolerated Dose (MTD) of Cyclophosphamide and ATO | 0 | 0 | 0 | 0 | 0 |
ORR defined by complete remission/complete remission with incomplete recovery of blood counts (CR/CRi), morphologic leukemia free state (MLFS) and partial responses (PR)
| Participants | Cohort -1 | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 |
|---|---|---|---|---|---|
| Overall Response Rate (ORR) Using ATO and Cyclophosphamide | — | 3 | 2 | — | — |
Collected over 26 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Cohort -1 | — | — | — |
| Cohort 1 | 0/3 (0%) | 1/3 (33.3%) | 3/3 (100%) |
| Cohort 2 | 0/2 (0%) | 0/2 (0%) | 2/2 (100%) |
| Cohort 3 | — | — | — |
| Cohort 4 | — | — | — |
| Event | Cohort -1 | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 |
|---|---|---|---|---|---|
| PneumoniaRespiratory, thoracic and mediastinal disorders | — | 1/3 | — | — | — |
| HypoxiaRespiratory, thoracic and mediastinal disorders | — | 1/3 | — | — | — |
| Chest PainRespiratory, thoracic and mediastinal disorders | — | 1/3 | — | — | — |
| Event | Cohort -1 | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 |
|---|---|---|---|---|---|
| EdemaBlood and lymphatic system disorders | — | 2/3 | 1/2 | — | — |
| epistaxisSkin and subcutaneous tissue disorders | — | 2/3 | 0/2 | — | — |
| FeverGeneral disorders | — | 2/3 | 0/2 | — | — |
| PainMusculoskeletal and connective tissue disorders | — | 1/3 | 1/2 | — | — |
| AnemiaBlood and lymphatic system disorders | — | 0/3 | 1/2 | — | — |
| AnorexiaGeneral disorders | — | 1/3 | 1/2 | — | — |
| CoughRespiratory, thoracic and mediastinal disorders | — | 1/3 | 1/2 | — | — |
| DehydrationMetabolism and nutrition disorders | — | 0/3 | 1/2 | — | — |
| DepressionPsychiatric disorders | — | 0/3 | 1/2 | — | — |
| Creatinine IncreaseRenal and urinary disorders | — | 0/3 | 1/2 | — | — |
Relapsed/Refractory Acute Myeloid Leukemia
| Age, Categorical(Participants) | Cohort -1 | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Total |
|---|---|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | — | — | 0 |
| Between 18 and 65 years | 0 | 0 | 0 | — | — | 0 |
| >=65 years | 0 | 3 | 2 | — | — | 5 |
| Age, Continuous(years) | Cohort -1 | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Total |
|---|---|---|---|---|---|---|
| Median | — | 72 (72 to 82) | 68 (68 to 86) | — | — | 78 (68 to 86) |
| Sex: Female, Male(Participants) | Cohort -1 | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Total |
|---|---|---|---|---|---|---|
| Female | — | 3 | 0 | — | — | 3 |
| Male | — | 0 | 2 | — | — | 2 |
| Ethnicity (NIH/OMB)(Participants) | Cohort -1 | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Total |
|---|---|---|---|---|---|---|
| Hispanic or Latino | — | 0 | 0 | — | — | 0 |
| Not Hispanic or Latino | — | 3 | 2 | — | — | 5 |
| Unknown or Not Reported | — | 0 | 0 | — | — | 0 |
| Race (NIH/OMB)(Participants) | Cohort -1 | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Total |
|---|---|---|---|---|---|---|
| American Indian or Alaska Native | — | 0 | 0 | — | — | 0 |
| Asian | — | 0 | 0 | — | — | 0 |
| Native Hawaiian or Other Pacific Islander | — | 0 | 0 | — | — | 0 |
| Black or African American | — | 0 | 0 | — | — | 0 |
| White | — | 3 | 2 | — | — | 5 |
| More than one race | — | 0 | 0 | — | — | 0 |
| Unknown or Not Reported | — | 0 | 0 | — | — | 0 |
| Region of Enrollment(participants) | Cohort -1 | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Total |
|---|---|---|---|---|---|---|
| United States | — | 3 | 2 | — | — | 5 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
Ran from Dec 2017 to primary completion in Jan 2020, 25 months.
Results were first posted in Aug 2024, 4 years 6 months after primary completion.
How these figures are worked out, and which studies are left out of them.
This study is terminated, as verified in Feb 2024. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Cyclophosphamide
University of Colorado, Denver →