Fludarabine / Total Body Irradiation Regimen for ALLO HCT in Acute Lymphoblastic Leukemia

Adult Lymphoblastic Lymphoma Clinical Trial

— FluTBI  

Official title:

Single Arm Phase II Study of Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation for Acute Lymphoblastic Leukemia (ALL) in Older Patients Using Fludarabine and Total Body Irradiation (FluTBI) Regimen

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01991457
• Other study ID #: UAB 1285
• Status: Completed
• Phase: Phase 2
• Start date: August 27, 2013
• Est. completion date: August 23, 2022

Study information

• Verified date: January 2024
• Source: University of Alabama at Birmingham
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this research is to test if the conditioning regimen, fludarabine and total body irradiation (FluTBI), can lead to a safer and more effective stem cell transplant treatment regimen for ALL patients older than 40 years of age and/or younger patients with high risk medical conditions. The primary objective is to establish the efficacy of allo HCT in older ALL patients using myeloablative FluTBI conditioning regimen. The investigators are also assessing the safety and toxicity of allo HCT in older ALL patients using myeloablative FluTBI conditioning regimen.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: August 23, 2022
• Est. primary completion date: January 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 65 Years

Eligibility

Inclusion Criteria:

• Disease Criteria:

• ALL in complete remission (CR) at the time of transplant. Remission is defined as "less than 5.0% bone marrow lymphoblasts by morphology," as determined by a bone marrow aspirate obtained within 2 weeks of study registration.

• Philadelphia chromosome positive ALL is allowed.

• Lymphoid blastic crisis of CML will be included (provided that patients achieve CR).

• Age Criteria: Equal or above age 40 and up to 65 years. If younger than 40, there must be comorbidities which preclude the patient to undergo CyTBI conditioning regimen.

• Organ Function Criteria: All organ function testing should be done within 28 days of study registration.

• Cardiac: Left ventricular ejection fraction (LVEF) = 50% by MUGA (Multi Gated Acquisition) scan or echocardiogram.

• Pulmonary: FEV1 (Forced expiratory volume in 1 second) and FVC (Forced vital capacity) = 50% predicted, DLCO (alveolar diffusion capacity for carbon monoxide) (corrected for hemoglobin) = 50% of predicted.

• Renal: The estimated creatinine clearance (CrCl) must be equal or greater than 60 mL/min/1.73 m2 as calculated by the Cockcroft-Gault Formula:

CrCl = (140-age) x weight (kg) x 0.85 (if female)/72 x serum creatinine (mg/dL).

• Hepatic:

• Serum bilirubin 2.0 g/dL

• Aspartate transaminase (AST)/alanine transaminase (ALT) 2.5 ULN

• Alkaline phosphatase 2.5 ULN

• Performance status: Karnofsky = 70%

• Consent: Patient must be informed of the investigational nature of this study in accordance with institutional and federal guidelines and have the ability to provide written informed consent prior to initiation of any study-related procedures, and ability,in the opinion of the principal investigator, to comply with all the requirements of the study.

• Presence of a willing adult HLA-matched sibling (excluding identical twin) or HLA-matched unrelated donor meeting all the criteria for routine allo HSCT. All donors will be evaluated for eligibility and suitability per the standard of care according to the FACT and NMDP guidelines.

Exclusion Criteria:

• Non-compliant to medications.

• No appropriate caregivers identified.

• HIV1 (Human Immunodeficiency Virus-1) or HIV2 positive

• Active life-threatening cancer requiring treatment other than ALL

• Uncontrolled medical or psychiatric disorders.

• Uncontrolled infections, defined as positive blood cultures within 72 hours of study entry, or evidence of progressive infection by imaging studies such as chest CT scan within 14 days of registration.

• Active central nervous system (CNS) leukemia

• Preceding allogeneic HSCT

• Receiving intensive chemotherapy within 21 days of registration. Maintenance type of chemotherapy will be allowed.

Related Conditions & MeSH terms

• Adult Lymphoblastic Lymphoma
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Fludarabine

Procedure:
• Total Body Irradiation

Locations

Country	Name	City	State
United States	UAB Bone Marrow Transplantation and Cellular Therapy Program	Birmingham	Alabama

Sponsors (1)

Lead Sponsor	Collaborator
University of Alabama at Birmingham

Country where clinical trial is conducted

United States, 

References & Publications (30)

Alousi A, de Lima M. Reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation. Clin Adv Hematol Oncol. 2007 Jul;5(7):560-70. — View Citation

Alvarnas JC, Brown PA, Aoun P, Ballen KK, Bellam N, Blum W, Boyer MW, Carraway HE, Coccia PF, Coutre SE, Cultrera J, Damon LE, DeAngelo DJ, Douer D, Frangoul H, Frankfurt O, Goorha S, Millenson MM, O'Brien S, Petersdorf SH, Rao AV, Terezakis S, Uy G, Wetzler M, Zelenetz AD, Naganuma M, Gregory KM; National Comprehensive Cancer Network. Acute lymphoblastic leukemia. J Natl Compr Canc Netw. 2012 Jul 1;10(7):858-914. doi: 10.6004/jnccn.2012.0089. — View Citation

Annino L, Vegna ML, Camera A, Specchia G, Visani G, Fioritoni G, Ferrara F, Peta A, Ciolli S, Deplano W, Fabbiano F, Sica S, Di Raimondo F, Cascavilla N, Tabilio A, Leoni P, Invernizzi R, Baccarani M, Rotoli B, Amadori S, Mandelli F; GIMEMA Group. Treatment of adult acute lymphoblastic leukemia (ALL): long-term follow-up of the GIMEMA ALL 0288 randomized study. Blood. 2002 Feb 1;99(3):863-71. doi: 10.1182/blood.v99.3.863. — View Citation

Arnold R, Massenkeil G, Bornhauser M, Ehninger G, Beelen DW, Fauser AA, Hegenbart U, Hertenstein B, Ho AD, Knauf W, Kolb HJ, Kolbe K, Sayer HG, Schwerdtfeger R, Wandt H, Hoelzer D. Nonmyeloablative stem cell transplantation in adults with high-risk ALL may be effective in early but not in advanced disease. Leukemia. 2002 Dec;16(12):2423-8. doi: 10.1038/sj.leu.2402712. — View Citation

Bachanova V, Weisdorf D. Unrelated donor allogeneic transplantation for adult acute lymphoblastic leukemia: a review. Bone Marrow Transplant. 2008 Mar;41(5):455-64. doi: 10.1038/sj.bmt.1705889. Epub 2007 Oct 29. — View Citation

Chaidos A, Kanfer E, Apperley JF. Risk assessment in haemotopoietic stem cell transplantation: disease and disease stage. Best Pract Res Clin Haematol. 2007 Jun;20(2):125-54. doi: 10.1016/j.beha.2006.10.003. — View Citation

Ciurea SO, Saliba RM, Hamerschlak N, Karduss Aurueta AJ, Bassett R, Fernandez-Vina M, Petropoulos D, Worth LL, Chan KW, Couriel DR, Rondon G, Sharma M, Qazilbash M, Jones RB, Kebriaei P, McMannis J, Hosing CM, Nieto Y, Champlin RE, Shpall EJ, de Lima M. Fludarabine, melphalan, thiotepa and anti-thymocyte globulin conditioning for unrelated cord blood transplant. Leuk Lymphoma. 2012 May;53(5):901-6. doi: 10.3109/10428194.2011.631159. Epub 2012 Jan 3. — View Citation

Davies SM, Ramsay NK, Klein JP, Weisdorf DJ, Bolwell B, Cahn JY, Camitta BM, Gale RP, Giralt S, Heilmann C, Henslee-Downey PJ, Herzig RH, Hutchinson R, Keating A, Lazarus HM, Milone GA, Neudorf S, Perez WS, Powles RL, Prentice HG, Schiller G, Socie G, Vowels M, Wiley J, Yeager A, Horowitz MM. Comparison of preparative regimens in transplants for children with acute lymphoblastic leukemia. J Clin Oncol. 2000 Jan;18(2):340-7. doi: 10.1200/JCO.2000.18.2.340. — View Citation

Devine SM, Sanborn R, Jessop E, Stock W, Huml M, Peace D, Wickrema A, Yassine M, Amin K, Thomason D, Chen YH, Devine H, Maningo M, van Besien K. Fludarabine and melphalan-based conditioning for patients with advanced hematological malignancies relapsing after a previous hematopoietic stem cell transplant. Bone Marrow Transplant. 2001 Sep;28(6):557-62. doi: 10.1038/sj.bmt.1703198. — View Citation

Fiere D, Lepage E, Sebban C, Boucheix C, Gisselbrecht C, Vernant JP, Varet B, Broustet A, Cahn JY, Rigal-Huguet F, et al. Adult acute lymphoblastic leukemia: a multicentric randomized trial testing bone marrow transplantation as postremission therapy. The French Group on Therapy for Adult Acute Lymphoblastic Leukemia. J Clin Oncol. 1993 Oct;11(10):1990-2001. doi: 10.1200/JCO.1993.11.10.1990. — View Citation

Gale RP, Horowitz MM. Graft-versus-leukemia in bone marrow transplantation. The Advisory Committee of the International Bone Marrow Transplant Registry. Bone Marrow Transplant. 1990 Jul;6 Suppl 1:94-7. — View Citation

Gaynon PS, Angiolillo AL, Carroll WL, Nachman JB, Trigg ME, Sather HN, Hunger SP, Devidas M; Children's Oncology Group. Long-term results of the children's cancer group studies for childhood acute lymphoblastic leukemia 1983-2002: a Children's Oncology Group Report. Leukemia. 2010 Feb;24(2):285-97. doi: 10.1038/leu.2009.262. Epub 2009 Dec 17. — View Citation

Goldstone AH, Richards SM, Lazarus HM, Tallman MS, Buck G, Fielding AK, Burnett AK, Chopra R, Wiernik PH, Foroni L, Paietta E, Litzow MR, Marks DI, Durrant J, McMillan A, Franklin IM, Luger S, Ciobanu N, Rowe JM. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood. 2008 Feb 15;111(4):1827-33. doi: 10.1182/blood-2007-10-116582. Epub 2007 Nov 29. — View Citation

Gutierrez-Aguirre CH, Gomez-Almaguer D, Cantu-Rodriguez OG, Gonzalez-Llano O, Jaime-Perez JC, Herena-Perez S, Manzano CA, Estrada-Gomez R, Gonzalez-Carrillo ML, Ruiz-Arguelles GJ. Non-myeloablative stem cell transplantation in patients with relapsed acute lymphoblastic leukemia: results of a multicenter study. Bone Marrow Transplant. 2007 Sep;40(6):535-9. doi: 10.1038/sj.bmt.1705769. Epub 2007 Jul 9. — View Citation

Hahn T, Wall D, Camitta B, Davies S, Dillon H, Gaynon P, Larson RA, Parsons S, Seidenfeld J, Weisdorf D, McCarthy PL Jr. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of acute lymphoblastic leukemia in adults: an evidence-based review. Biol Blood Marrow Transplant. 2006 Jan;12(1):1-30. doi: 10.1016/j.bbmt.2005.10.018. — View Citation

Hamaki T, Kami M, Kanda Y, Yuji K, Inamoto Y, Kishi Y, Nakai K, Nakayama I, Murashige N, Abe Y, Ueda Y, Hino M, Inoue T, Ago H, Hidaka M, Hayashi T, Yamane T, Uoshima N, Miyakoshi S, Taniguchi S. Reduced-intensity stem-cell transplantation for adult acute lymphoblastic leukemia: a retrospective study of 33 patients. Bone Marrow Transplant. 2005 Mar;35(6):549-56. doi: 10.1038/sj.bmt.1704776. — View Citation

Horowitz MM, Gale RP, Sondel PM, Goldman JM, Kersey J, Kolb HJ, Rimm AA, Ringden O, Rozman C, Speck B, et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood. 1990 Feb 1;75(3):555-62. — View Citation

Kroger N, Bornhauser M, Ehninger G, Schwerdtfeger R, Biersack H, Sayer HG, Wandt H, Schafer-Eckardt K, Beyer J, Kiehl M, Zander AR; German Cooperative Transplant Study Group. Allogeneic stem cell transplantation after a fludarabine/busulfan-based reduced-intensity conditioning in patients with myelodysplastic syndrome or secondary acute myeloid leukemia. Ann Hematol. 2003 Jun;82(6):336-42. doi: 10.1007/s00277-003-0654-9. Epub 2003 May 1. — View Citation

Larson RA, Dodge RK, Burns CP, Lee EJ, Stone RM, Schulman P, Duggan D, Davey FR, Sobol RE, Frankel SR, et al. A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: cancer and leukemia group B study 8811. Blood. 1995 Apr 15;85(8):2025-37. — View Citation

Marks DI, Forman SJ, Blume KG, Perez WS, Weisdorf DJ, Keating A, Gale RP, Cairo MS, Copelan EA, Horan JT, Lazarus HM, Litzow MR, McCarthy PL, Schultz KR, Smith DD, Trigg ME, Zhang MJ, Horowitz MM. A comparison of cyclophosphamide and total body irradiation with etoposide and total body irradiation as conditioning regimens for patients undergoing sibling allografting for acute lymphoblastic leukemia in first or second complete remission. Biol Blood Marrow Transplant. 2006 Apr;12(4):438-53. doi: 10.1016/j.bbmt.2005.12.029. — View Citation

Martino R, Giralt S, Caballero MD, Mackinnon S, Corradini P, Fernandez-Aviles F, San Miguel J, Sierra J. Allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning in acute lymphoblastic leukemia: a feasibility study. Haematologica. 2003 May;88(5):555-60. — View Citation

Mohty M, Labopin M, Tabrizzi R, Theorin N, Fauser AA, Rambaldi A, Maertens J, Slavin S, Majolino I, Nagler A, Blaise D, Rocha V; Acute Leukemia Working Party; European Group for Blood and Marrow Transplantation. Reduced intensity conditioning allogeneic stem cell transplantation for adult patients with acute lymphoblastic leukemia: a retrospective study from the European Group for Blood and Marrow Transplantation. Haematologica. 2008 Feb;93(2):303-6. doi: 10.3324/haematol.11960. — View Citation

Nakamura Y, Mori T, Kato J, Aisa Y, Nakazato T, Shigematsu N, Okamoto S. [Allogeneic hematopoietic stem cell transplantation with fludarabine, melphalan, and total body irradiation as a conditioning for elderly patients with myeloid malignancies]. Rinsho Ketsueki. 2012 Mar;53(3):318-22. Japanese. — View Citation

Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995 Jun;15(6):825-8. — View Citation

Ram R, Storb R, Sandmaier BM, Maloney DG, Woolfrey A, Flowers ME, Maris MB, Laport GG, Chauncey TR, Lange T, Langston AA, Storer B, Georges GE. Non-myeloablative conditioning with allogeneic hematopoietic cell transplantation for the treatment of high-risk acute lymphoblastic leukemia. Haematologica. 2011 Aug;96(8):1113-20. doi: 10.3324/haematol.2011.040261. Epub 2011 Apr 20. — View Citation

Ringden O, Labopin M, Tura S, Arcese W, Iriondo A, Zittoun R, Sierra J, Gorin NC. A comparison of busulphan versus total body irradiation combined with cyclophosphamide as conditioning for autograft or allograft bone marrow transplantation in patients with acute leukaemia. Acute Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Br J Haematol. 1996 Jun;93(3):637-45. doi: 10.1046/j.1365-2141.1996.d01-1681.x. — View Citation

Sebban C, Lepage E, Vernant JP, Gluckman E, Attal M, Reiffers J, Sutton L, Racadot E, Michallet M, Maraninchi D, et al. Allogeneic bone marrow transplantation in adult acute lymphoblastic leukemia in first complete remission: a comparative study. French Group of Therapy of Adult Acute Lymphoblastic Leukemia. J Clin Oncol. 1994 Dec;12(12):2580-7. doi: 10.1200/JCO.1994.12.12.2580. — View Citation

Snyder DS, Nademanee AP, O'Donnell MR, Parker PM, Stein AS, Margolin K, Somlo G, Molina A, Spielberger R, Kashyap A, Fung H, Slovak ML, Dagis A, Negrin RS, Amylon MD, Blume KG, Forman SJ. Long-term follow-up of 23 patients with Philadelphia chromosome-positive acute lymphoblastic leukemia treated with allogeneic bone marrow transplant in first complete remission. Leukemia. 1999 Dec;13(12):2053-8. doi: 10.1038/sj.leu.2401589. — View Citation

Stelljes M, Bornhauser M, Kroger M, Beyer J, Sauerland MC, Heinecke A, Berning B, Scheffold C, Silling G, Buchner T, Neubauer A, Fauser AA, Ehninger G, Berdel WE, Kienast J; Cooperative German Transplant Study Group. Conditioning with 8-Gy total body irradiation and fludarabine for allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia. Blood. 2005 Nov 1;106(9):3314-21. doi: 10.1182/blood-2005-04-1377. Epub 2005 Jul 14. — View Citation

Yanada M, Matsuo K, Suzuki T, Naoe T. Allogeneic hematopoietic stem cell transplantation as part of postremission therapy improves survival for adult patients with high-risk acute lymphoblastic leukemia: a metaanalysis. Cancer. 2006 Jun 15;106(12):2657-63. doi: 10.1002/cncr.21932. — View Citation

* Note: There are 30 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Subjects Disease-free Survival	Percentage of patients without relapse of disease at 2 years	2 years post-transplant
Secondary	Percentage of Subjects That Survived		2 years post-transplant
Secondary	Time to Neutrophil Engraftment	Neutrophil engraftment is defined as the first of 3 consecutive days with an absolute neutrophil count (ANC) > 500/µL. Measuring the number of days it takes for (ANC) > 500/µL.	Within the first 100 days
Secondary	Number of Subjects With Regimen Related Toxicity		Within first 100 days post-transplant
Secondary	Percentage of Subjects With Acute GVHD		2 years post transplant
Secondary	Number of Patients With Immune Reconstitution		1 year post transplant
Secondary	Percentage of Subjects With Relapse		2 Years post-transplant
Secondary	Number of Subjects With Platelet Engraftment	Platelet engraftment is defined as the first of 3 consecutive days with a platelet count > 20,000/µL without platelet transfusion for 7 days.	Within 100 days post transplant
Secondary	Percentage of Subjects With Chronic GVHD		2 years post transplant

External Links

•   UAB Bone Marrow Transplantation and Cell Therapy Program