NCT05497310

Brief 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. In this study we intent to demonstrate the effectiveness of combined therapy of low-dose ATRA plus attenuated dose ATO.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
15

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Jul 2022

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2022

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

August 9, 2022

Completed
2 days until next milestone

First Posted

Study publicly available on registry

August 11, 2022

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2025

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

July 31, 2025

Completed
Last Updated

October 26, 2022

Status Verified

October 1, 2022

Enrollment Period

3 years

First QC Date

August 9, 2022

Last Update Submit

October 24, 2022

Conditions

Promyelocytic Leukemia

Keywords

all-trans retinoic acidarsenic trioxidefrontline therapyinduction chemotherapy

Outcome Measures

Primary Outcomes (1)

  • Incidence of Treatment-Emergent Adverse Events

    Safety will be defined by the number of patients deceased after 1 induction cycle of 28 days

    28 days

Secondary Outcomes (4)

  • Overall response

    28 days

  • Progression-free survival

    6 months

  • Event-free survival

    6 months

  • Rate of treatment discontinuation due to toxicity.

    28 days

Study Arms (1)

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).

Drug: Arsenic trioxideDrug: all-trans retinoic acid

Interventions

Arsenic trioxideDRUG

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).

Also known as: Trisenox
Induction with attenuated ATO plus low-dose ATRA
all-trans retinoic acidDRUG

Patients will receive ATRA 25/mg/m2/day for 28 continuous days without interruption.

Also known as: Vesanoid
Induction with attenuated ATO plus low-dose ATRA

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • Acute myocardial infarction, unstable angina, or stable angina in the last six months
  • Uncontrolled active infection
  • Liver disease (Child-Pugh C)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hopsital Universitario Dr. Jose E. Gonzalez, Centro Universitario contra el Cancer

Monterrey, Nuevo León, 64460, Mexico

RECRUITING

Related Publications (6)

  • 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.

    PMID: 3165295BACKGROUND

  • Chen 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.

    PMID: 8704214BACKGROUND

  • Castaigne 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.

    PMID: 8260694BACKGROUND

  • Chen 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.

    PMID: 8656678BACKGROUND

  • Jaime-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.

    PMID: 26500134BACKGROUND

  • Burnett 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.

    PMID: 26384238BACKGROUND

MeSH Terms

Conditions

Leukemia, Promyelocytic, Acute

Interventions

Arsenic TrioxideTretinoin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid, AcuteLeukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

ArsenicalsInorganic ChemicalsOxidesOxygen CompoundsVitamin ARetinoidsCarotenoidsPolyenesAlkenesHydrocarbons, AcyclicHydrocarbonsOrganic ChemicalsCyclohexenesCyclohexanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicTerpenesDiterpenesPigments, BiologicalBiological Factors

Central Study Contacts

Edgar Coronado-Alejandro, MD

CONTACT

8441077402edgar.coronado.al@gmail.com

Andrés Gómez de León, MD

CONTACT

818470002drgomezdeleon@gmail.com

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Masking Details
This is an Open label study
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Model Details: 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.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Head of Hematology Service

Study Record Dates

First Submitted

August 9, 2022

First Posted

August 11, 2022

Study Start

July 1, 2022

Primary Completion

June 30, 2025

Study Completion

July 31, 2025

Last Updated

October 26, 2022

Record last verified: 2022-10

Data Sharing

IPD Sharing
Will not share

Locations

ME(1)