Promyelocytic LeukemiaPhase 1/2NCT05497310
Effectiveness and Safety of Therapy Based on Attenuated ATO Plus Low-Dose ATRA in Patients With APL
A Phase 1/2 study testing Arsenic trioxide and all-trans retinoic acid in people with Promyelocytic Leukemia, run by Hospital Universitario Dr. Jose E. Gonzalez at 1 site in Mexico.
Trial summary
ATRA is the standard of care for all patients with APL. The use of lower doses of ATRA has been shown since the 1990s to achieve therapeutic efficacy with doses of 25mg/m2/day. ATO demonstrated considerable effectiveness in this disease. More recently, an attenuated regimen has been proven to be effective. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Promyelocytic Leukemia
- What is being tested?
- Arsenic trioxide and all-trans retinoic acid
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteMexico
- Study dates
- 1 Jul 2022to 31 Jul 2025
- Phase
- Phase 1/2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age >18 years
- Both genders
- new diagnosis of APL
- Diagnosis of relapsed APL who have not been previously treated with ATO
- Morphological diagnosis of APL confirmed by PCR or FISH
Who cannot join
- Poor functional status (ECOG>2)
- Organic dysfunction (Marshall score ≥2)
- Pregnancy
- Heart failure (NYHA III or IV)
- Renal failure (GFR <30 ml/min/1.72m2)
- History of ventricular arrhythmias or uncontrolled arrhythmias
Show all 9Show fewer
- Acute myocardial infarction, unstable angina, or stable angina in the last six months
- Uncontrolled active infection
- Liver disease (Child-Pugh C)
Trial locations and contacts
1 site in 1 country.
Mexico1 site, 1 recruiting
- Recruiting
Hopsital Universitario Dr. Jose E. Gonzalez, Centro Universitario contra el Cancer
Monterrey, Nuevo León, 64460
David Gomez-Almaguer, MD, +52 81 8348-8510, dgomezalmaguer@gmail.com
Andres Gomez, MD, 818470002, drgomezdeleon@gmail.com
About this study
Official title: Effectiveness and Safety of Therapy Based on Attenuated Arsenic Trioxide Plus Low Doses of All-trans Retinoic Acid as Remission Induction Therapy in Patients With Acute Promyelocytic Leukemia Phase 1/2 Clinical Trial
ATRA is the standard of care for all patients with APL. The use of lower doses of ATRA has been shown since the 1990s to achieve therapeutic efficacy with doses of 25mg/m2/day. ATO demonstrated considerable effectiveness in this disease. More recently, an attenuated regimen has been proven to be effective. In this study we intent to demonstrate the effectiveness of combined therapy of low-dose ATRA plus attenuated dose ATO.
Read the detailed description
The use of lower doses of ATRA has been shown since the 1990s to achieve therapeutic plasma concentrations sufficient to achieve therapeutic efficacy with doses of 25mg/m2/day. ATO alone demonstrated considerable effectiveness in this disease. More recently, an attenuated regimen has been proven to be effective in inducing similar remission rates and achieving prolonged survival, also demonstrating a reduction in associated toxicities, mainly hepatic and cardiac when using this new scheme.
The investigators will conduct a phase 1/2, non-randomized, single center, non-comparative clinical trial to demonstrate the effectiveness of combined therapy of low-dose ATRA plus attenuated dose ATO which is accessible to a population with limited resources while maintaining acceptable efficacy and safety.
- Conditions
- Promyelocytic Leukemia
- Being tested
- Arsenic trioxide, all-trans retinoic acid
- Keywords
- all-trans retinoic acid, arsenic trioxide, frontline therapy, induction chemotherapy
- Medical subject headings
- Leukemia, Promyelocytic, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Arsenic trioxideDrug
Also called Trisenox
Patients will receive ATO 0.3mg/kg/day for days 1-5 (5 doses) and then 0.25 mg/kg/day every other day twice a week for the next 3 weeks (6 doses).
all-trans retinoic acidDrug
Also called Vesanoid
Patients will receive ATRA 25/mg/m2/day for 28 continuous days without interruption.
| Study group | Role | What they receive |
|---|---|---|
| Induction with attenuated ATO plus low-dose ATRA | Experimental | Remission induction therapy will be administrated as ATRA 25/mg/m2/day for 28 continuous days without interruption if APL is suspected. ATO 0.3mg/kg/day for days 1-5 (5 doses) and then 0.25 mg/kg/day every other day twice a week for the next 3 weeks (6 doses). Receives: Drug: Arsenic trioxide; Drug: all-trans retinoic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events
Safety will be defined by the number of patients deceased after 1 induction cycle of 28 days
Measured: 28 days
Secondary outcomes (4)
Overall response
Overall response rate was definide as partial response plus complete response after 1
Measured: 28 days
Progression-free survival
Time from achievement of complete hematologic remission to relapse
Measured: 6 months
Event-free survival
Time from registration to induction failure, relapse, or death.
Measured: 6 months
Rate of treatment discontinuation due to toxicity.
Rate of treatment discontinuation due to toxicity.
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2022
- Study start1 Jul 2022
- Primary completion30 Jun 2025 (estimated)
- Study completion31 Jul 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Promyelocytic LeukemiaStudies of the same condition, open and under way.
- 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
- Model description
- A consecutive sample of 15 patients with newly diagnosed or relapsed APL who have not been previously treated with ATO will be prospectively included in this study.
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital Universitario Dr. Jose E. Gonzalez
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David Gomez Almaguer, Hospital Universitario Dr. Jose E. Gonzalez
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05497310
- Sponsor's protocol ID
- HE22-00019
- Status last verified
- Oct 2022
- First submitted
- 9 Aug 2022
- Last updated
- 26 Oct 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Huang ME, Ye YC, Chen SR, Chai JR, Lu JX, Zhoa L, Gu LJ, Wang ZY. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood. 1988 Aug;72(2):567-72.
PubMed 3165295Chen GQ, Zhu J, Shi XG, Ni JH, Zhong HJ, Si GY, Jin XL, Tang W, Li XS, Xong SM, Shen ZX, Sun GL, Ma J, Zhang P, Zhang TD, Gazin C, Naoe T, Chen SJ, Wang ZY, Chen Z. In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins. Blood. 1996 Aug 1;88(3):1052-61.
PubMed 8704214Castaigne S, Lefebvre P, Chomienne C, Suc E, Rigal-Huguet F, Gardin C, Delmer A, Archimbaud E, Tilly H, Janvier M, et al. Effectiveness and pharmacokinetics of low-dose all-trans retinoic acid (25 mg/m2) in acute promyelocytic leukemia. Blood. 1993 Dec 15;82(12):3560-3.
PubMed 8260694Chen GQ, Shen ZX, Wu F, Han JY, Miao JM, Zhong HJ, Li XS, Zhao JQ, Zhu J, Fang ZW, Chen SJ, Chen Z, Wang ZY. Pharmacokinetics and efficacy of low-dose all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Leukemia. 1996 May;10(5):825-8.
PubMed 8656678Jaime-Perez JC, Gonzalez-Leal XJ, Pinzon-Uresti MA, Gomez-De Leon A, Cantu-Rodriguez OG, Gutierrez-Aguirre H, Gomez-Almaguer D. Is There Still a Role for Low-Dose All-Transretinoic Acid in the Treatment of Acute Promyelocytic Leukemia in the Arsenic Trioxide Era? Clin Lymphoma Myeloma Leuk. 2015 Dec;15(12):816-9. doi: 10.1016/j.clml.2015.09.002. Epub 2015 Sep 25.
PubMed 26500134Burnett AK, Russell NH, Hills RK, Bowen D, Kell J, Knapper S, Morgan YG, Lok J, Grech A, Jones G, Khwaja A, Friis L, McMullin MF, Hunter A, Clark RE, Grimwade D; UK National Cancer Research Institute Acute Myeloid Leukaemia Working Group. Arsenic trioxide and all-trans retinoic acid treatment for acute promyelocytic leukaemia in all risk groups (AML17): results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2015 Oct;16(13):1295-305. doi: 10.1016/S1470-2045(15)00193-X. Epub 2015 Sep 14.
PubMed 26384238
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effectiveness and Safety of Therapy Based on Attenuated Arsenic Trioxide Plus Low Doses of All-trans Retinoic Acid as Remission Induction Therapy in Patients With Acute Promyelocytic Leukemia Phase 1/2 Clinical Trial
- ClinicalTrials.gov ID
- NCT05497310
- Acronym / sponsor ID
- HE22-00019
- Conditions
- Promyelocytic Leukemia
- Keywords
- all-trans retinoic acid, arsenic trioxide, frontline therapy, induction chemotherapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Hospital Universitario Dr. Jose E. GonzalezUniversity, hospital or other
- Study start
- 1 Jul 2022 (actual)
- Primary completion
- 30 Jun 2025 (estimated)
- Study completion
- 31 Jul 2025 (estimated)
- First posted
- 11 Aug 2022 (actual)
- 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.
ATRA is the standard of care for all patients with APL. The use of lower doses of ATRA has been shown since the 1990s to achieve therapeutic efficacy with doses of 25mg/m2/day. ATO demonstrated considerable effectiveness in this disease. More recently, an attenuated regimen has been proven to be effective. In this study we intent to demonstrate the effectiveness of combined therapy of low-dose ATRA plus attenuated dose ATO.
Detailed description
The use of lower doses of ATRA has been shown since the 1990s to achieve therapeutic plasma concentrations sufficient to achieve therapeutic efficacy with doses of 25mg/m2/day. ATO alone demonstrated considerable effectiveness in this disease. More recently, an attenuated regimen has been proven to be effective in inducing similar remission rates and achieving prolonged survival, also demonstrating a reduction in associated toxicities, mainly hepatic and cardiac when using this new scheme.
The investigators will conduct a phase 1/2, non-randomized, single center, non-comparative clinical trial to demonstrate the effectiveness of combined therapy of low-dose ATRA plus attenuated dose ATO which is accessible to a population with limited resources while maintaining acceptable efficacy and safety.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- A consecutive sample of 15 patients with newly diagnosed or relapsed APL who have not been previously treated with ATO will be prospectively included in this study.
| Arm | Type | Receives |
|---|---|---|
| Induction with attenuated ATO plus low-dose ATRA | Experimental | Drug: Arsenic trioxide, Drug: all-trans retinoic acidRemission induction therapy will be administrated as ATRA 25/mg/m2/day for 28 continuous days without interruption if APL is suspected. ATO 0.3mg/kg/day for days 1-5 (5 doses) and then 0.25 mg/kg/day every other day twice a week for the next 3 weeks (6 doses). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age >18 years
- Both genders
- new diagnosis of APL
- Diagnosis of relapsed APL who have not been previously treated with ATO
- Morphological diagnosis of APL confirmed by PCR or FISH
Key exclusion criteria (9 listed)
- Poor functional status (ECOG>2)
- Organic dysfunction (Marshall score ≥2)
- Pregnancy
- Heart failure (NYHA III or IV)
- Renal failure (GFR <30 ml/min/1.72m2)
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 |
|---|---|---|
| Arsenic trioxideAlso: TrisenoxPatients will receive ATO 0.3mg/kg/day for days 1-5 (5 doses) and then 0.25 mg/kg/day every other day twice a week for the next 3 weeks (6 doses). | Drug | Induction with attenuated ATO plus low-dose ATRA |
| all-trans retinoic acidAlso: VesanoidPatients will receive ATRA 25/mg/m2/day for 28 continuous days without interruption. | Drug | Induction with attenuated ATO plus low-dose ATRA |
Primary outcome
Incidence of Treatment-Emergent Adverse Events
Time frame: 28 days
Safety will be defined by the number of patients deceased after 1 induction cycle of 28 days
4 secondary outcomes
Overall response
Time frame: 28 days
Progression-free survival
Time frame: 6 months
Event-free survival
Time frame: 6 months
Rate of treatment discontinuation due to toxicity.
Time frame: 28 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2022.
- Background: PubMed 3165295Huang ME, Ye YC, Chen SR, Chai JR, Lu JX, Zhoa L, Gu LJ, Wang ZY. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood. 1988 Aug;72(2):567-72.
- Background: PubMed 8704214Chen GQ, Zhu J, Shi XG, Ni JH, Zhong HJ, Si GY, Jin XL, Tang W, Li XS, Xong SM, Shen ZX, Sun GL, Ma J, Zhang P, Zhang TD, Gazin C, Naoe T, Chen SJ, Wang ZY, Chen Z. In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins. Blood. 1996 Aug 1;88(3):1052-61.
- Background: PubMed 8260694Castaigne S, Lefebvre P, Chomienne C, Suc E, Rigal-Huguet F, Gardin C, Delmer A, Archimbaud E, Tilly H, Janvier M, et al. Effectiveness and pharmacokinetics of low-dose all-trans retinoic acid (25 mg/m2) in acute promyelocytic leukemia. Blood. 1993 Dec 15;82(12):3560-3.
- Background: PubMed 8656678Chen GQ, Shen ZX, Wu F, Han JY, Miao JM, Zhong HJ, Li XS, Zhao JQ, Zhu J, Fang ZW, Chen SJ, Chen Z, Wang ZY. Pharmacokinetics and efficacy of low-dose all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Leukemia. 1996 May;10(5):825-8.
- Background: PubMed 26500134Jaime-Perez JC, Gonzalez-Leal XJ, Pinzon-Uresti MA, Gomez-De Leon A, Cantu-Rodriguez OG, Gutierrez-Aguirre H, Gomez-Almaguer D. Is There Still a Role for Low-Dose All-Transretinoic Acid in the Treatment of Acute Promyelocytic Leukemia in the Arsenic Trioxide Era? Clin Lymphoma Myeloma Leuk. 2015 Dec;15(12):816-9. doi: 10.1016/j.clml.2015.09.002. Epub 2015 Sep 25.
- Background: PubMed 26384238Burnett AK, Russell NH, Hills RK, Bowen D, Kell J, Knapper S, Morgan YG, Lok J, Grech A, Jones G, Khwaja A, Friis L, McMullin MF, Hunter A, Clark RE, Grimwade D; UK National Cancer Research Institute Acute Myeloid Leukaemia Working Group. Arsenic trioxide and all-trans retinoic acid treatment for acute promyelocytic leukaemia in all risk groups (AML17): results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2015 Oct;16(13):1295-305. doi: 10.1016/S1470-2045(15)00193-X. Epub 2015 Sep 14.
- 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.
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 Arsenic trioxide and all-trans retinoic acid in people with Promyelocytic Leukemia, run by Hospital Universitario Dr. Jose E. Gonzalez at 1 site in Mexico.
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 9 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: status not confirmed, as of the sponsor's last update on 26 Oct 2022. 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 Mexico. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Edgar Coronado-Alejandro, MD (8441077402, edgar.coronado.al@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Events (time frame: 28 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 NCT05497310, which also lists 6 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 26 Oct 2022.