Treatment of Newly Diagnosed Patients With Acute Promyelocytic Leukemia (PETHEMA LPA 2005)
Study Details
Study Description
Brief Summary
Primary objectives
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To evaluate the efficacy and toxicity of a risk-adapted protocol that use idarubicin for induction and consolidation therapy in patients with APL.
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To evaluate the impact of mitoxantrone reduction on the event-free, disease-free, and overall survival, as well as on the duration of remission and cumulative incidence of relapse in low- and intermediate-risk patients with APL.
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To evaluate the impact of the addition of ara-C to idarubicin courses of consolidation for high-risk patients (administered as in the original GIMEMA protocols) on the event-free, disease-free, and overall survival, as well as on the duration of remission and cumulative incidence of relapse.
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To evaluate the toxicity of the induction, consolidation, and maintenance chemotherapy in the whole series and in each treatment group in patients with APL.
Secondary objectives
• To compare all outcomes with those achieved with the PETHEMA LPA99 protocol.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 4 |
Detailed Description
Treatment of induction with the simultaneous administration of ATRA (45 mg/m2 day until the RC) and idarubicine (12 mg/m2 days 2, 4, 6 and 8), 3 monthly cycles of consolidation with ATRA (45 mg/m2 days 1-15) and idarubicine (5 mg/m2 days 1-4) in the cycle #1, mitoxantrone (10 mg/m2 days 1-3) in the cycle #2 and idarubicine (12 mg/m2 day 1) in the cycle #3. The consolidation was reinforced for the group of patients with intermediate risk by means of an increase of the idarubicine to 7 mg in the cycle #1 and to 2 days in the cycle #3. In the patients of high risk, the consolidation was reinforced with the addition of altar-c in the cycles #1 and #3. For the maintenance treatment, one will administer to intermittent ATRA (15 days every 3 months) and chemotherapy low doses with methotrexate and 6-mercaptopurina during two years
Study Design
Outcome Measures
Primary Outcome Measures
- To evaluate the efficacy and toxicity of a risk-adapted protocol that use idarubicin for induction and consolidation therapy in patients with APL. [1 year]
- To evaluate the impact of mitoxantrone reduction on the event-free, disease-free, and overall survival. [1 year]
- To evaluate the impact of the addition of ara-C to idarubicin courses of consolidation for high-risk patients on the event-free, disease-free, and overall survival [1 year]
- To evaluate the toxicity of the induction, consolidation, and maintenance chemotherapy in the whole series and in each treatment group in patients with APL. [1 year]
Secondary Outcome Measures
- To compare all outcomes with those achieved with the PETHEMA LPA99 protocol. [2 years]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age ≤ 75 years.
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ECOG ≤ 3.
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Morphologic Diagnosis of LPA (FAB M3 or variant M3). Those cases without typical morphology but with PML-RARα reordering also must be including.
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Genetic Diagnosis: t (15; 17) demonstrated by cariotipo conventional, FISH, PML-RARα reordering detected by RT-PCR or a pattern microspeckled demonstrated with antibody anti-PML (positive PGM3). Obvious, it will be had the result of these tests once initiated the treatment on the basis of a suspicion diagnoses morphologic
Exclusion Criteria:
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Age >75 years (the treatment with this protocol can be considered individually)
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Absence of PML-Rare reordering.
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To have received previously some type of treatment for LPA, including chemotherapy or retinoides. The previous treatment with corticoids, hidroxiurea or leucoaféresis is not reason for exclusion.
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To have received chemotherapy or x-ray for the treatment of a disease vitiates previous.
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Associate Neoplasia.
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Serious psychiatric Disease.
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Seropositividad for VIH.
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Contraindication to receive intensive chemotherapy, specially antraciclinas.
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Sérica Creatinina ≥ 2,5 mg/dL (≥ 250 μmol/l).
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Bilirrubina, fosfatasa alkaline, or GOT > 3 times the normal limit
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Test of positive pregnancy.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | PALG | Lodz | Poland | ||
2 | Hospital General | Albacete | Spain | ||
3 | Hospital general | Alicante | Spain | ||
4 | Hospital germans Trias i Pujol | Badalona | Spain | ||
5 | Hospital Clinic | Barcelona | Spain | ||
6 | Hospital de Sant Pau | Barcelona | Spain | ||
7 | Institut Català d'Oncologái | Barcelona | Spain | ||
8 | Basurtuko Ospitalea | Bilbao | Spain | ||
9 | Hospital general | Castellon | Spain | ||
10 | Hospital de Fuenlabrada | Fuenlabrada | Spain | ||
11 | Hospital "Dr. Trueta" | Gerona | Spain | ||
12 | Hospital de Jerez de la Frontera | Jerez de la Frontera | Spain | ||
13 | Hospital Juan Canalejo | La Coruña | Spain | ||
14 | Hospital Insular de las Palmas | Las Palmas de Gran Canaria | Spain | ||
15 | Complejo Hospitalario León | Leon | Spain | ||
16 | Complexo Hospitalario Xeral-Calde | Lugo | Spain | ||
17 | Hospital 12 de Octubre | Madrid | Spain | ||
18 | Hospital Clínico San Carlos | Madrid | Spain | ||
19 | Hospital Puerta de Hierro | Madrid | Spain | ||
20 | Hospital Reina Sofia | Madrid | Spain | ||
21 | Hospital San Pedro de Alcántara | Madrid | Spain | ||
22 | Hospital Severo Ochoa | Madrid | Spain | ||
23 | Hospital Sta. Maria del Rosell | Murcia | Spain | ||
24 | H. Carlos Haya | Málaga | Spain | ||
25 | H. Universitario Virgen de la Victoria | Málaga | Spain | ||
26 | Hospital Central de Asturias | Oviedo | Spain | ||
27 | Hospital Dr Negrín | Palma de Gran Canaria | Spain | ||
28 | Hospital de Navarra | Pamplona | Spain | ||
29 | Hospital de Montecelo | Pontevedra | Spain | ||
30 | Hospital Clínico Universitario | Salamanca | Spain | ||
31 | Hospital de Cruces | Santander | Spain | ||
32 | Hospital de Santiago de Compostela | Santiago de Compostela | Spain | ||
33 | H.U. Virgen del Rocio | Sevilla | Spain | ||
34 | Hospital Joan XXIII | Tarragona | Spain | ||
35 | Hospital Dr. Peset | Valencia | Spain | ||
36 | Hospital general | Valencia | Spain | ||
37 | Hospital La Fe | Valencia | Spain | ||
38 | Hospital Clínico de Valladolid | Valladolid | Spain | ||
39 | Hospital Txagorritxu | Vitoria | Spain | ||
40 | Hospital Virgen de la Concha | Zamora | Spain | ||
41 | Hospital Clínico Universitario Lozano Blesa | Zaragoza | Spain | ||
42 | Hospital Maciel | Montevideo | Uruguay |
Sponsors and Collaborators
- PETHEMA Foundation
Investigators
- Study Chair: San Miguel Miguel Angel, Dr, HOSPITAL LA FE VALENCIA
- Study Director: Vellenga Edo, Dr, Stichting Hemato-Oncologie voor Volwassenen Nederland
- Study Director: Lowenberg Bob, Dr, Stichting Hemato-Oncologie voor Volwassenen Nederland
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- Asou N, Adachi K, Tamura J, Kanamaru A, Kageyama S, Hiraoka A, Omoto E, Akiyama H, Tsubaki K, Saito K, Kuriyama K, Oh H, Kitano K, Miyawaki S, Takeyama K, Yamada O, Nishikawa K, Takahashi M, Matsuda S, Ohtake S, Suzushima H, Emi N, Ohno R. Analysis of prognostic factors in newly diagnosed acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy. Japan Adult Leukemia Study Group. J Clin Oncol. 1998 Jan;16(1):78-85.
- Burnett AK, Grimwade D, Solomon E, Wheatley K, Goldstone AH. Presenting white blood cell count and kinetics of molecular remission predict prognosis in acute promyelocytic leukemia treated with all-trans retinoic acid: result of the Randomized MRC Trial. Blood. 1999 Jun 15;93(12):4131-43.
- Falini B, Flenghi L, Fagioli M, Lo Coco F, Cordone I, Diverio D, Pasqualucci L, Biondi A, Riganelli D, Orleth A, Liso A, Martelli MF, Pelicci PG, Pileri S. Immunocytochemical diagnosis of acute promyelocytic leukemia (M3) with the monoclonal antibody PG-M3 (anti-PML). Blood. 1997 Nov 15;90(10):4046-53.
- Fenaux P, Chastang C, Chevret S, Sanz M, Dombret H, Archimbaud E, Fey M, Rayon C, Huguet F, Sotto JJ, Gardin C, Makhoul PC, Travade P, Solary E, Fegueux N, Bordessoule D, Miguel JS, Link H, Desablens B, Stamatoullas A, Deconinck E, Maloisel F, Castaigne S, Preudhomme C, Degos L. A randomized comparison of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia. The European APL Group. Blood. 1999 Aug 15;94(4):1192-200.
- Gomis F, Sanz J, Sempere A, Plumé G, Senent ML, Pérez ML, Cervera J, Moscardó F, Bolufer P, Barragán E, Martín G, Sanz MA. Immunofluorescent analysis with the anti-PML monoclonal antibody PG-M3 for rapid and accurate genetic diagnosis of acute promyelocytic leukemia. Ann Hematol. 2004 Nov;83(11):687-90. Epub 2004 Jul 24.
- Grimwade D, Gorman P, Duprez E, Howe K, Langabeer S, Oliver F, Walker H, Culligan D, Waters J, Pomfret M, Goldstone A, Burnett A, Freemont P, Sheer D, Solomon E. Characterization of cryptic rearrangements and variant translocations in acute promyelocytic leukemia. Blood. 1997 Dec 15;90(12):4876-85.
- Lengfelder E, Reichert A, Schoch C, Haase D, Haferlach T, Löffler H, Staib P, Heyll A, Seifarth W, Saussele S, Fonatsch C, Gassmann W, Ludwig WD, Hochhaus A, Beelen D, Aul C, Sauerland MC, Heinecke A, Hehlmann R, Wörmann B, Hiddemann W, Büchner T. Double induction strategy including high dose cytarabine in combination with all-trans retinoic acid: effects in patients with newly diagnosed acute promyelocytic leukemia. German AML Cooperative Group. Leukemia. 2000 Aug;14(8):1362-70.
- Ohno R, Asou N, Ohnishi K. Treatment of acute promyelocytic leukemia: strategy toward further increase of cure rate. Leukemia. 2003 Aug;17(8):1454-63. Review.
- Sanz MA, Lo Coco F, Martín G, Avvisati G, Rayón C, Barbui T, Díaz-Mediavilla J, Fioritoni G, González JD, Liso V, Esteve J, Ferrara F, Bolufer P, Bernasconi C, Gonzalez M, Rodeghiero F, Colomer D, Petti MC, Ribera JM, Mandelli F. Definition of relapse risk and role of nonanthracycline drugs for consolidation in patients with acute promyelocytic leukemia: a joint study of the PETHEMA and GIMEMA cooperative groups. Blood. 2000 Aug 15;96(4):1247-53.
- Sanz MA, Martín G, González M, León A, Rayón C, Rivas C, Colomer D, Amutio E, Capote FJ, Milone GA, De La Serna J, Román J, Barragán E, Bergua J, Escoda L, Parody R, Negri S, Calasanz MJ, Bolufer P; Programa de Estudio y Traitmiento de las Hemopatías Malignas. Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA group. Blood. 2004 Feb 15;103(4):1237-43. Epub 2003 Oct 23.
- Sanz MA, Martín G, Lo Coco F. Choice of chemotherapy in induction, consolidation and maintenance in acute promyelocytic leukaemia. Best Pract Res Clin Haematol. 2003 Sep;16(3):433-51. Review.
- Tallman MS, Nabhan C, Feusner JH, Rowe JM. Acute promyelocytic leukemia: evolving therapeutic strategies. Blood. 2002 Feb 1;99(3):759-67. Review.
- van Dongen JJ, Macintyre EA, Gabert JA, Delabesse E, Rossi V, Saglio G, Gottardi E, Rambaldi A, Dotti G, Griesinger F, Parreira A, Gameiro P, Diáz MG, Malec M, Langerak AW, San Miguel JF, Biondi A. Standardized RT-PCR analysis of fusion gene transcripts from chromosome aberrations in acute leukemia for detection of minimal residual disease. Report of the BIOMED-1 Concerted Action: investigation of minimal residual disease in acute leukemia. Leukemia. 1999 Dec;13(12):1901-28. Review.
- LPA 2005