Clinical trial NCT05049473: Treatment of Mature B-ALL and Burkitt Lymphoma (BL) in Adult Patients. BURKIMAB-14.
Official title: Treatment of Mature B-ALL and Burkitt Lymphoma (BL) in Adult Patients. BURKIMAB-14.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Mature B-Cell Leukemia Burkitt Type
Burkitt Lymphoma (BL)
Unclassifiable Lymphoma Between DCBL and BL
Keywords: Mature B-ALL
Burkitt lymphoma
Adult
Lead sponsor: PETHEMA Foundation
Sponsor class: OTHER
Collaborators: name: Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
First posted: 2021-09-20
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Rituximab combined with a specific intensive chemotherapy is considered the standard treatment for newly diagnosed patients with mature B leukemia/lymphoma. However, the toxicity of this therapy is high. The purpose of this trial is to reduce the dose intensity of the chemotherapy blocks once the patient has achieved complete response. With this approach the investigators expect to maintain the efficacy and to reduce the toxicity of the chemotherapy, specially the rate of deaths in complete response.

Detailed description: Patients younger than 55 years in complete response after two blocks of rituximab and specific intensive chemotherapy will receive four additional blocks of rituximab and attenuated chemotherapy (reduction by 33% of the dose of cyclophosphamide, methotrexate and cytarabine) followed by additional rituximab doses as consolidation. Patients older than 55 years will receive the six blocks with attenuated chemotherapy.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years old
* Patients diagnosed with de novo mature B-ALL, Burkitt lymphoma (BL). Under physician's criteria, patients with unclassified B-lymphoma with intermediate characteristics between DLBCL and BL could be included.
* Candidate to intensive treatment.

Exclusion Criteria:

* Other ALL subtype different from mature B-ALL/BL
* Severe complications not due to mature B-ALL/BL (eg, sepsis, pneumonia, shock or hemorrhage) at diagnosis.
* Renal failure not due to mature B-ALL /BL
* Heart or liver failure
* Severe lung disease
* Secondary mature B-ALL/BL
* Hypersensitivity to foreign proteins
* Previous treatment with cytotoxic drugs
* Pregnancy/breastfeeding
* Severe psychiatric disease
* Lack of social or familiar support

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Throughout the study period. Approximately 3 years
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Throughout the study period. Approximately 3 years
measure: Number of patients with toxicity during the treatment period.
timeFrame: Throughout the study period. Approximately 3 years
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital de Sant Pau
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Bellvitge
country: Spain
facility: ICO-Hospital Duran i Reynals
city: Bilbao
country: Spain
facility: Hospital Universitario de Basurto
city: Cáceres
country: Spain
facility: Hospital San Pedro de Alcántara
city: Córdoba
country: Spain
facility: Hospital Reina Sofía
city: Donostia
country: Spain
facility: Hospital Universitario de Donostia
city: Las Palmas De Gran Canaria
country: Spain
facility: Hospital Universitario de Gran Canaria Dr Negrín
city: Lleida
country: Spain
facility: Hospital Arnau de Vilanova (Lleida)
city: Madrid
country: Spain
facility: Hospital 12 De Octubre
city: Madrid
country: Spain
facility: Hospital Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital La Zarzuela
city: Madrid
country: Spain
facility: Hospital Madrid Norte Sanchinarro
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario La Princesa
city: Málaga
country: Spain
facility: Hospital Clínico de Málaga
city: Oviedo
country: Spain
facility: Hospital Central de Asturias
city: Palma De Mallorca
country: Spain
facility: Son Llàtzer
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: San Sebastián De Los Reyes
country: Spain
facility: Hospital Universitario Infanta Sofía
city: Santiago De Compostela
country: Spain
facility: Complexo Hospitalario Santiago de Compostela
city: Tarragona
country: Spain
facility: ICO-Hospital Joan XXIII
city: Terrassa
country: Spain
facility: Mútua de Terrassa
city: Torrejón De Ardoz
country: Spain
facility: Hospital Universitario de Torrejón
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
city: Ávila
country: Spain
facility: Hospital Nuestra Señora de Sonsoles
Study officials:
affiliation: ICO-Hospital Germans Trias i Pujol
name: JOSEP MARIA RIBERA SANTASUSANA, M.D.; Ph.D.
role: STUDY_CHAIR
affiliation: ICO-Hospital Germans Trias i Pujol
name: JUAN MANUEL SANCHO CIA, M.D.; Ph.D.
role: STUDY_CHAIR
References:
citation: Sancho JM, Ribera JM. Linfoma de Burkitt. En: Manual Práctico de Hematología Clínica. 4ª edición 2012.
citation: WHO Classification of Tumours of Haematopoietics and Lymphoid Tissues, 2008.
citation: Karantanis D, Durski JM, Lowe VJ, Nathan MA, Mullan BP, Georgiou E, Johnston PB, Wiseman GA. 18F-FDG PET and PET/CT in Burkitt's lymphoma. Eur J Radiol. 2010 Jul;75(1):e68-73. doi: 10.1016/j.ejrad.2009.07.035. Epub 2009 Aug 27.
citation: Zeng W, Lechowicz MJ, Winton E, Cho SM, Galt JR, Halkar R. Spectrum of FDG PET/CT findings in Burkitt lymphoma. Clin Nucl Med. 2009 Jun;34(6):355-8. doi: 10.1097/RLU.0b013e3181a34552.
citation: Just PA, Fieschi C, Baillet G, Galicier L, Oksenhendler E, Moretti JL. 18F-fluorodeoxyglucose positron emission tomography/computed tomography in AIDS-related Burkitt lymphoma. AIDS Patient Care STDS. 2008 Sep;22(9):695-700. doi: 10.1089/apc.2008.0174.
citation: Hoelzer D, Ludwig WD, Thiel E, Gassmann W, Loffler H, Fonatsch C, Rieder H, Heil G, Heinze B, Arnold R, Hossfeld D, Buchner T, Koch P, Freund M, Hiddemann W, Maschmeyer G, Heyll A, Aul C, Faak T, Kuse R, Ittel TH, Gramatzki M, Diedrich H, Kolbe K, Fuhr HG, Fischer K, Schadeck-Gressel C, Weiss A, Strohscheer I, Metzner B, Fabry U, Gokbuget N, Volkers B, Messerer D, Uberla K. Improved outcome in adult B-cell acute lymphoblastic leukemia. Blood. 1996 Jan 15;87(2):495-508.
citation: Reiter A, Schrappe M, Tiemann M, Ludwig WD, Yakisan E, Zimmermann M, Mann G, Chott A, Ebell W, Klingebiel T, Graf N, Kremens B, Muller-Weihrich S, Pluss HJ, Zintl F, Henze G, Riehm H. Improved treatment results in childhood B-cell neoplasms with tailored intensification of therapy: A report of the Berlin-Frankfurt-Munster Group Trial NHL-BFM 90. Blood. 1999 Nov 15;94(10):3294-306.
citation: Thomas DA, Cortes J, O'Brien S, Pierce S, Faderl S, Albitar M, Hagemeister FB, Cabanillas FF, Murphy S, Keating MJ, Kantarjian H. Hyper-CVAD program in Burkitt's-type adult acute lymphoblastic leukemia. J Clin Oncol. 1999 Aug;17(8):2461-70. doi: 10.1200/JCO.1999.17.8.2461.
citation: Adde M, Shad A, Venzon D, Arndt C, Gootenberg J, Neely J, Nieder M, Owen W, Seibel N, Wilson W, Horak ID, Magrath I. Additional chemotherapy agents improve treatment outcome for children and adults with advanced B-cell lymphomas. Semin Oncol. 1998 Apr;25(2 Suppl 4):33-9; discussion 45-8.
citation: Lee EJ, Petroni GR, Schiffer CA, Freter CE, Johnson JL, Barcos M, Frizzera G, Bloomfield CD, Peterson BA. Brief-duration high-intensity chemotherapy for patients with small noncleaved-cell lymphoma or FAB L3 acute lymphocytic leukemia: results of cancer and leukemia group B study 9251. J Clin Oncol. 2001 Oct 15;19(20):4014-22. doi: 10.1200/JCO.2001.19.20.4014.
citation: Ribera JM, Garcia O, Grande C, Esteve J, Oriol A, Bergua J, Gonzalez-Campos J, Vall-Llovera F, Tormo M, Hernandez-Rivas JM, Garcia D, Brunet S, Alonso N, Barba P, Miralles P, Llorente A, Montesinos P, Moreno MJ, Hernandez-Rivas JA, Bernal T. Dose-intensive chemotherapy including rituximab in Burkitt's leukemia or lymphoma regardless of human immunodeficiency virus infection status: final results of a phase 2 study (Burkimab). Cancer. 2013 May 1;119(9):1660-8. doi: 10.1002/cncr.27918. Epub 2013 Jan 29.
citation: Hoelzer D, Walewski J, Döhner H, Schmid M, Hiddemann W, Baumann A, et al. Substantially improved outcome of adult Burkitt Non-Hodgkin lymphoma and leukemia patients with rituximab and a short-intensive chemotherapy; Report of a large prospective multicenter trial. Fifty-four annual meeting of American Society of Hematology. Abstract 667
citation: Intermesoli T, Rambaldi A, Rossi G, Delaini F, Romani C, Pogliani EM, Pagani C, Angelucci E, Terruzzi E, Levis A, Cassibba V, Mattei D, Gianfaldoni G, Scattolin AM, Di Bona E, Oldani E, Parolini M, Gokbuget N, Bassan R. High cure rates in Burkitt lymphoma and leukemia: a Northern Italy Leukemia Group study of the German short intensive rituximab-chemotherapy program. Haematologica. 2013 Nov;98(11):1718-25. doi: 10.3324/haematol.2013.086827. Epub 2013 Jun 10.
citation: Oriol A, Ribera JM, Esteve J, Sanz MA, Brunet S, Garcia-Boyero R, Fernandez-Abellan P, Marti JM, Abella E, Sanchez-Delgado M, Penarrubia MJ, Besalduch J, Moreno MJ, Borrego D, Feliu E, Ortega JJ; PETHEMA Group, Spanish Society of Hematology. Lack of influence of human immunodeficiency virus infection status in the response to therapy and survival of adult patients with mature B-cell lymphoma or leukemia. Results of the PETHEMA-LAL3/97 study. Haematologica. 2003 Apr;88(4):445-53.
citation: Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V; International Harmonization Project on Lymphoma. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007 Feb 10;25(5):579-86. doi: 10.1200/JCO.2006.09.2403. Epub 2007 Jan 22.
citation: Bleyer WA. New vistas for leucovorin in cancer chemotherapy. Cancer. 1989 Mar 15;63(6 Suppl):995-1007. doi: 10.1002/1097-0142(19890315)63:6+3.0.co;2-r.
citation: Pauley JL, Panetta JC, Crews KR, Pei D, Cheng C, McCormick J, Howard SC, Sandlund JT, Jeha S, Ribeiro R, Rubnitz J, Pui CH, Evans WE, Relling MV. Between-course targeting of methotrexate exposure using pharmacokinetically guided dosage adjustments. Cancer Chemother Pharmacol. 2013 Aug;72(2):369-78. doi: 10.1007/s00280-013-2206-x. Epub 2013 Jun 13.
citation: Reiter A, Schrappe M, Ludwig WD, Tiemann M, Parwaresch R, Zimmermann M, Schirg E, Henze G, Schellong G, Gadner H, Riehm H. Intensive ALL-type therapy without local radiotherapy provides a 90% event-free survival for children with T-cell lymphoblastic lymphoma: a BFM group report. Blood. 2000 Jan 15;95(2):416-21.
citation: Pauley JL, Panetta JC, Schmidt J, Kornegay N, Relling MV, Pui CH. Late-onset delayed excretion of methotrexate. Cancer Chemother Pharmacol. 2004 Aug;54(2):146-52. doi: 10.1007/s00280-004-0797-y. Epub 2004 May 18.
citation: Pinedo HM, Zaharko DS, Bull JM, Chabner BA. The reversal of methotrexate cytotoxicity to mouse bone marrow cells by leucovorin and nucleosides. Cancer Res. 1976 Dec;36(12):4418-24.
citation: Scott JR, Zhou Y, Cheng C, Ward DA, Swanson HD, Molinelli AR, Stewart CF, Navid F, Jeha S, Relling MV, Crews KR. Comparable efficacy with varying dosages of glucarpidase in pediatric oncology patients. Pediatr Blood Cancer. 2015 Sep;62(9):1518-22. doi: 10.1002/pbc.25395. Epub 2015 Jan 28.