The Acute Promyelocytic Leukaemia Asian Consortium (APL-AC) Project

Acute Promyelocytic Leukemia Clinical Trial

Official title:

The Acute Promyelocytic Leukaemia Asian Consortium (APL-AC) Project

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04251754
• Other study ID #: APLAC001
• Status: Recruiting
• Start date: February 2, 2020
• Est. completion date: June 2025

Study information

• Verified date: October 2022
• Source: The University of Hong Kong
• Contact: Harinder Singh Harry Gill, MD
• Phone: +852 22554542
• Email: gillhsh[@]hku.hk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

There is currently lack of collaborative data on the epidemiology, clinicopathologic features and treatment outcome of newly diagnosed and relapsed APL in Asia. In addition, there is lack of data comparing oral- As2O3-based regimens with other treatment approaches, including intravenous As2O3,in the frontline or relapsed setting. With the long-term data of oral-As2O3 based regimen for APL available from Hong Kong, retrospective and prospective comparison with other treatment approaches in other Asian countries will generate important information to pave the way for widespread application of oral-As2O3 outside Hong Kong.

Description:

Acute promyelocytic leukemia (APL) is characterized by t(15;17)(q24;21) and the fusion gene PML-RARA.1 In newly-diagnosed patients, optimal supportive care together with the use of all-trans retinoic acid (ATRA) and chemotherapy results in first complete remission (CR1) in excess of 90% with durable remissions in about 80% of patients.Arsenic trioxide (As2O3) given intravenously (i.v.-As2O3) is highly efficacious for APL in first relapse (R1), inducing second complete remission (CR2) in more than 90% of patients. We have formulated an oral preparation of As2O3 (oral-As2O3), and shown that it is efficacious for APL in R1, giving CR2 rates of more than 90% in both adults and children. For patients in CR2, a 2-year maintenance with oral-As2O3 results in durable remission and long-term survivals in more than 60% and 70% of patients respectively strongly suggesting that hematopoietic stem cell transplantation (HSCT) could be obviated in such patients. With these results, we implemented oral-As2O3 maintenance in CR1 in Hong Kong and demonstrated very favourable overall-survival (OS) and leukemia-free-survival (LFS). This implied that that prolonged oral-As2O3 treatment may prevent relapses.

Meanwhile, i.v.-As2O3 has also been tested in the frontline treatment of newly-diagnosed APL.These studies employed different strategies, recruiting a mixture of low-, intermediate- to high-risk patients and placing i.v.-As2O3 in induction and/or consolidation. During induction, i.v.-As2O3 was combined with ATRA, with additional gemtuzumab ozogamicin (an anti-CD33 immunoconjugate) or chemotherapy. During consolidation, i.v.-As2O3 was combined with conventional chemotherapy. Their results all indicated that frontline use of i.v.-As2O3 in induction and/or consolidation improved the outcome of newly-diagnosed APL patients. However, with quite diverse protocols and the enrollment in some studies of only patients with low to intermediate risks, and in other studies of patients with all risk categories; the optimal strategy of employing i.v.-As2O3 in newly-diagnosed APL remains to be defined. We have tested oral- As2O3 in combination with ATRA, ascorbic acid (AAA) with daunorubicin in both low-risk and high-risk APL with 3 year LFS and OS of both 100%.

With the impressive results of oral-As2O3-based regimen in newly diagnosed and relapsed APL, an important future perspective is the application of this relatively economical and convenient approach to the treatment of patients with APL in Asia and other developing countries around the world where the cost and availability of intravenous formulation of As2O3 is a concern. There is currently lack of collaborative data on the epidemiology, clinicopathologic features and treatment outcome of newly diagnosed and relapsed APL in Asia. In addition, there is lack of data comparing oral- As2O3-based regimens with other treatment approaches, including intravenous As2O3,in the frontline or relapsed setting. With the long-term data of oral-As2O3 based regimen for APL available from Hong Kong, retrospective and prospective comparison with other treatment approaches in other Asian countries will generate important information to pave the way for widespread application of oral-As2O3 outside Hong Kong.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: June 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion criteria:

• Patients aged 18 or above

• Acute promyelocytic leukaemia with PML/RARA

• Acute myeloid leukaemia with variant RARA translocation

Exclusion criteria:

-Acute myeloid leukaemia without PML/RARA or variant RARA translocation

Related Conditions & MeSH terms

• Acute Promyelocytic Leukemia
• Leukemia
• Leukemia, Promyelocytic, Acute

Locations

Country	Name	City	State
Hong Kong	Department of Medicine, the University of Hong Kong, Queen Mary Hospital	Hong Kong

Sponsors (1)

Lead Sponsor	Collaborator
The University of Hong Kong

Country where clinical trial is conducted

Hong Kong, 

References & Publications (17)

Abaza Y, Kantarjian H, Garcia-Manero G, Estey E, Borthakur G, Jabbour E, Faderl S, O'Brien S, Wierda W, Pierce S, Brandt M, McCue D, Luthra R, Patel K, Kornblau S, Kadia T, Daver N, DiNardo C, Jain N, Verstovsek S, Ferrajoli A, Andreeff M, Konopleva M, Es — View Citation

Au WY, Kumana CR, Lee HK, Lin SY, Liu H, Yeung DY, Lau JS, Kwong YL. Oral arsenic trioxide-based maintenance regimens for first complete remission of acute promyelocytic leukemia: a 10-year follow-up study. Blood. 2011 Dec 15;118(25):6535-43. doi: 10.1182 — View Citation

Au WY, Li CK, Lee V, Yuen HL, Yau J, Chan GC, Ha SY, Kwong YL. Oral arsenic trioxide for relapsed acute promyelocytic leukemia in pediatric patients. Pediatr Blood Cancer. 2012 Apr;58(4):630-2. doi: 10.1002/pbc.23306. Epub 2011 Sep 2. — View Citation

Gill H, Kumana CR, Yim R, Hwang YY, Chan TSY, Yip SF, Lee HKK, Mak V, Lau JSM, Chan CC, Kho B, Wong RSM, Li W, Lin SY, Lau CK, Ip HW, Leung RYY, Lam CCK, Kwong YL. Oral arsenic trioxide incorporation into frontline treatment with all-trans retinoic acid a — View Citation

Gill H, Yim R, Lee HKK, Mak V, Lin SY, Kho B, Yip SF, Lau JSM, Li W, Ip HW, Hwang YY, Chan TSY, Tse E, Au WY, Kumana CR, Kwong YL. Long-term outcome of relapsed acute promyelocytic leukemia treated with oral arsenic trioxide-based reinduction and maintena — View Citation

Hu J, Liu YF, Wu CF, Xu F, Shen ZX, Zhu YM, Li JM, Tang W, Zhao WL, Wu W, Sun HP, Chen QS, Chen B, Zhou GB, Zelent A, Waxman S, Wang ZY, Chen SJ, Chen Z. Long-term efficacy and safety of all-trans retinoic acid/arsenic trioxide-based therapy in newly diag — View Citation

Iland HJ, Bradstock K, Supple SG, Catalano A, Collins M, Hertzberg M, Browett P, Grigg A, Firkin F, Hugman A, Reynolds J, Di Iulio J, Tiley C, Taylor K, Filshie R, Seldon M, Taper J, Szer J, Moore J, Bashford J, Seymour JF; Australasian Leukaemia and Lymp — View Citation

Kelaidi C, Chevret S, De Botton S, Raffoux E, Guerci A, Thomas X, Pigneux A, Lamy T, Rigal-Huguet F, Meyer-Monard S, Chevallier P, Maloisel F, Deconinck E, Ferrant A, Fegueux N, Ifrah N, Sanz M, Dombret H, Fenaux P, Adès L. Improved outcome of acute promy — View Citation

Lengfelder E, Haferlach C, Saussele S, Haferlach T, Schultheis B, Schnittger S, Ludwig WD, Staib P, Aul C, Grüneisen A, Kern W, Reichle A, Serve H, Berdel WE, Braess J, Spiekermann K, Wörmann B, Sauerland MC, Heinecke A, Hiddemann W, Hehlmann R, Büchner T — View Citation

Lo-Coco F, Avvisati G, Vignetti M, Breccia M, Gallo E, Rambaldi A, Paoloni F, Fioritoni G, Ferrara F, Specchia G, Cimino G, Diverio D, Borlenghi E, Martinelli G, Di Raimondo F, Di Bona E, Fazi P, Peta A, Bosi A, Carella AM, Fabbiano F, Pogliani EM, Petti — View Citation

Lo-Coco F, Avvisati G, Vignetti M, Thiede C, Orlando SM, Iacobelli S, Ferrara F, Fazi P, Cicconi L, Di Bona E, Specchia G, Sica S, Divona M, Levis A, Fiedler W, Cerqui E, Breccia M, Fioritoni G, Salih HR, Cazzola M, Melillo L, Carella AM, Brandts CH, Morr — View Citation

Niu C, Yan H, Yu T, Sun HP, Liu JX, Li XS, Wu W, Zhang FQ, Chen Y, Zhou L, Li JM, Zeng XY, Yang RR, Yuan MM, Ren MY, Gu FY, Cao Q, Gu BW, Su XY, Chen GQ, Xiong SM, Zhang TD, Waxman S, Wang ZY, Chen Z, Hu J, Shen ZX, Chen SJ. Studies on treatment of acute — View Citation

Platzbecker U, Avvisati G, Cicconi L, Thiede C, Paoloni F, Vignetti M, Ferrara F, Divona M, Albano F, Efficace F, Fazi P, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Sali — View Citation

Powell BL, Moser B, Stock W, Gallagher RE, Willman CL, Stone RM, Rowe JM, Coutre S, Feusner JH, Gregory J, Couban S, Appelbaum FR, Tallman MS, Larson RA. Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemi — View Citation

Soignet SL, Frankel SR, Douer D, Tallman MS, Kantarjian H, Calleja E, Stone RM, Kalaycio M, Scheinberg DA, Steinherz P, Sievers EL, Coutré S, Dahlberg S, Ellison R, Warrell RP Jr. United States multicenter study of arsenic trioxide in relapsed acute promy — View Citation

Tallman MS, Altman JK. How I treat acute promyelocytic leukemia. Blood. 2009 Dec 10;114(25):5126-35. doi: 10.1182/blood-2009-07-216457. — View Citation

Tallman MS, Andersen JW, Schiffer CA, Appelbaum FR, Feusner JH, Woods WG, Ogden A, Weinstein H, Shepherd L, Willman C, Bloomfield CD, Rowe JM, Wiernik PH. All-trans retinoic acid in acute promyelocytic leukemia: long-term outcome and prognostic factor ana — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survivals	The primary outcome measures in this study include the overall survival (OS) and the relapse-free survival (RFS). OS is defined as the time (in months) from diagnosis to death from any cause (event) or latest follow-up. RFS is defined as the time from first complete remission (CR)/complete remission with incomplete haematological recovery (CRi) to first hamatologic relapse or molecular relapse (R1) (event), death from any cause (event) or latest follow-up (censor). CR, CRi, treatment failure, haematologic relapse are defined according to the 2017 European LeukemiaNet (ELN) recommendations. A molecular relapse is defined as recurrence of measurable residual disease (MRD) by reverse-transcriptase polymerase chain reaction (RT-PCR) or real-time quantitative PCR (qRT PCR). A single MRD positivity must be confirmed by performing the molecular assay within 2 weeks.	60 months