Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
Recruitment Status
TERMINATED
Clinical Phase
PHASE2
Total Enrollment
72 participants
Study Classification
INTERVENTIONAL
Study Start Date
2003-09-30
Study Completion Date
2009-11-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
The primary aim of the study was to compare the efficacy of the procedure in terms of event-free survival between patients receiving cyclosporine (CsA) plus either alemtuzumab (CAMPATH-1H ) or methotrexate (MTX) after matched related donor allo-reduced intensity conditioning. Secondary aims were: 1. To compare the incidence of infections and transplant-related mortality between the two arms; 2. to compare the incidence of acute and chronic GVHD 3. to evaluate hematologic and immunologic reconstitution and evolution of chimerism and residual disease.
Patients were randomly assigned to received cyclosporine plus alemtuzumab or cyclosporine plus MTX and were stratified according to diagnosis: Chronic lymphocytic leukemia or Low grade- non-Hodgkin's lymphoma.
All patients received the same reduced-intensity conditioning (RIC) scheme based on fludarabine 150mg/m2 (30 mg/m2/day everyday from -8 to -4) plus melphalan 140mg/m2 (70 mg/m2/day everyday from -3 to -2). Regarding the GVHD prophylaxis, patients in group 1 (n=17) received CsA 1 mg/kg intravenously starting on day -7 and 2/mg/Kg from day -1 plus alemtuzumab administered at a dose of 20 mg IV on -8 to -4 whereas in group 2 (n=23) pts received CsA at same doses as group 1 plus MTX given at a dose of 15 mg/m2 intravenously on days 1 and 10 mg/m2 on days 3, 6 and 11, followed by folinic acid rescue (15 mg in +1 and 10 mg in +3, +6 and +11 intravenously every 6 hours for 4 doses starting 24 hours after each dose of MTX).
Acute and chronic GVHD were similarly graded by established criteria \[20, 21\]. In patients receiving alemtuzumab, CsA was suspended by day +130. They also received donor lymphocyte infusion (DLI) at a dose of 1 x 107 cluster of differentiation 3 / kg on day +180 in case of active disease, persistence of minimal residual disease detected by flow cytometry or mixed chimerism and no GVHD. In case mixed chimerism, donor lymphocyte infusion was performed if patient hematopoiesis progressively increased. In patients receiving CsA + MTX, CsA was suspended by day +180. These patients received DLI only in situations specified above.
The statistical analysis has been designed to identify a 20% difference in terms of disease-free survival (based on the increased incidence of relapse in patients receiving T-cell depletion).
Patients were randomly assigned to received cyclosporine plus alemtuzumab or cyclosporine plus MTX and were stratified according to diagnosis: Chronic lymphocytic leukemia or Low grade- non-Hodgkin's lymphoma.
All patients received the same reduced-intensity conditioning (RIC) scheme based on fludarabine 150mg/m2 (30 mg/m2/day everyday from -8 to -4) plus melphalan 140mg/m2 (70 mg/m2/day everyday from -3 to -2). Regarding the GVHD prophylaxis, patients in group 1 (n=17) received CsA 1 mg/kg intravenously starting on day -7 and 2/mg/Kg from day -1 plus alemtuzumab administered at a dose of 20 mg IV on -8 to -4 whereas in group 2 (n=23) pts received CsA at same doses as group 1 plus MTX given at a dose of 15 mg/m2 intravenously on days 1 and 10 mg/m2 on days 3, 6 and 11, followed by folinic acid rescue (15 mg in +1 and 10 mg in +3, +6 and +11 intravenously every 6 hours for 4 doses starting 24 hours after each dose of MTX).
Acute and chronic GVHD were similarly graded by established criteria \[20, 21\]. In patients receiving alemtuzumab, CsA was suspended by day +130. They also received donor lymphocyte infusion (DLI) at a dose of 1 x 107 cluster of differentiation 3 / kg on day +180 in case of active disease, persistence of minimal residual disease detected by flow cytometry or mixed chimerism and no GVHD. In case mixed chimerism, donor lymphocyte infusion was performed if patient hematopoiesis progressively increased. In patients receiving CsA + MTX, CsA was suspended by day +180. These patients received DLI only in situations specified above.
The statistical analysis has been designed to identify a 20% difference in terms of disease-free survival (based on the increased incidence of relapse in patients receiving T-cell depletion).
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Unrecognized Condition: Mature B or T-cell Neoplasm
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
conditioning treatment
alemtuzumab
allogeneic hematopoietic stem cell transplantation
chronic lymphoproliferative disorders
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
Allocation Method
RANDOMIZED
Intervention Model
PARALLEL
Primary Study Purpose
TREATMENT
Blinding Strategy
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Cyclosporine + METHOTREXATE
MTX days +1, +3, +6 and +11 followed by folinic acid rescue. All patients will receive CSA from day -7.
Group Type
ACTIVE_COMPARATOR
Cyclosporine + METHOTREXATE
Intervention Type
DRUG
MTX days +1, +3, +6 and +11 followed by rescue with folinic Ac. All patients receive CSA from day -7.
Cyclosporine + CAMPATH-1H
CAMPATH-1H at a dose of 20 mg / day at 8-hour intravenous infusion on days -8 to -4. All patients will receive CSA from day -7.
Group Type
EXPERIMENTAL
Cyclosporine + CAMPATH-1H
Intervention Type
DRUG
CAMPATH-1H at a dose of 20 mg / day at 8-hour intravenous infusion on days -8 to -4. All patients will receive CSA from day -7.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Cyclosporine + METHOTREXATE
MTX days +1, +3, +6 and +11 followed by rescue with folinic Ac. All patients receive CSA from day -7.
Intervention Type
DRUG
Cyclosporine + CAMPATH-1H
CAMPATH-1H at a dose of 20 mg / day at 8-hour intravenous infusion on days -8 to -4. All patients will receive CSA from day -7.
Intervention Type
DRUG
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Alemtuzumab
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
1. Having an identical Human Leukocyte Antigens (HLA) or a mismatched family donor.
2. Age between 45 and 65 years (outside this age range at the discretion of each center).
3. Indications:
* Follicular lymphoma with one of the following characteristics:
1. Poor prognosis follicular NHL (3 or more factors by Federico et al: erythrocyte sedimentation rate (ESR)\> 30, male,\> 60 years, high LDH\> 2 extranodal areas, pathologic stage (PS) \>2 or The International Prognostic Index (IPI) 3 or high lactate dehydrogenase (LDH) or micro Beta 2) failing to achieve CR with regimens including fludarabine and anti CD20 (cluster of differentiation antigen 20 ).
2. 2nd CR (complete response) or PR (partial response) not candidates for autologous transplantation;
3. persistent disease or relapse after autologous transplantation.
* Other low-grade lymphomas:
1. relapsed after autologous transplantation.
2. autologous transplant candidates which can not be performed because of the inability to collect a sufficient number of cells, steam cells disease persistence, etc..
* Chronic lymphocytic leukemia with one of the following characteristics:
1. "B" symptoms: weight loss \>10% in the last 6 months, fever \>38ºC (degrees centigrade) for 14 days without infection, night sweats without infection
2. lymphadenopathy \>10 cm or progressive, progressive splenomegaly
3. Anemia and/or thrombocytopenia secondary to bone marrow infiltration
4. Diffuse lymphocytic infiltration of the bone marrow
6. Patients with poor prognostic cytogenetic abnormalities: 17p-, 11q-with VDJ unmutated
4. Patients must also meet the following general requirements:
1. Performance status \<3 (Zubrod score, Eastern Cooperative Oncology Group (ECOG) performance status or WHO (World Health Organization) )
2. forced expiratory volume at one second (FEV1) \> 39%, lung diffusing capacity for carbon monoxide (DLCO) and forced vital capacity (FVC) \> 39% of the theoretical values
3. Total bilirubin and transaminases \<3 x the normal maximum value, unless attributable to base haemopathy
4. Creatinine \<2 x normal maximum and clearance\> 40 mL / min unless attributable to his base haemopathy
5. No evidence of symptomatic disease, cirrhosis or active hepatitis
6. Negative serology for HIV
7. Written informed consent
2. Age between 45 and 65 years (outside this age range at the discretion of each center).
3. Indications:
* Follicular lymphoma with one of the following characteristics:
1. Poor prognosis follicular NHL (3 or more factors by Federico et al: erythrocyte sedimentation rate (ESR)\> 30, male,\> 60 years, high LDH\> 2 extranodal areas, pathologic stage (PS) \>2 or The International Prognostic Index (IPI) 3 or high lactate dehydrogenase (LDH) or micro Beta 2) failing to achieve CR with regimens including fludarabine and anti CD20 (cluster of differentiation antigen 20 ).
2. 2nd CR (complete response) or PR (partial response) not candidates for autologous transplantation;
3. persistent disease or relapse after autologous transplantation.
* Other low-grade lymphomas:
1. relapsed after autologous transplantation.
2. autologous transplant candidates which can not be performed because of the inability to collect a sufficient number of cells, steam cells disease persistence, etc..
* Chronic lymphocytic leukemia with one of the following characteristics:
1. "B" symptoms: weight loss \>10% in the last 6 months, fever \>38ºC (degrees centigrade) for 14 days without infection, night sweats without infection
2. lymphadenopathy \>10 cm or progressive, progressive splenomegaly
3. Anemia and/or thrombocytopenia secondary to bone marrow infiltration
4. Diffuse lymphocytic infiltration of the bone marrow
6. Patients with poor prognostic cytogenetic abnormalities: 17p-, 11q-with VDJ unmutated
4. Patients must also meet the following general requirements:
1. Performance status \<3 (Zubrod score, Eastern Cooperative Oncology Group (ECOG) performance status or WHO (World Health Organization) )
2. forced expiratory volume at one second (FEV1) \> 39%, lung diffusing capacity for carbon monoxide (DLCO) and forced vital capacity (FVC) \> 39% of the theoretical values
3. Total bilirubin and transaminases \<3 x the normal maximum value, unless attributable to base haemopathy
4. Creatinine \<2 x normal maximum and clearance\> 40 mL / min unless attributable to his base haemopathy
5. No evidence of symptomatic disease, cirrhosis or active hepatitis
6. Negative serology for HIV
7. Written informed consent
Exclusion Criteria
1. Impaired hepatic or renal function superior to that described above
2. Presence of serious diseases that prevent chemotherapy treatments
3. Presence of psychiatric comorbidity
4. HIV infection
5. Other prior neoplasm
6. Do not have signed informed consent
7. Pregnant or at risk of pregnancy by inadequate contraceptive measures.
8. Patients diagnosed with chronic lymphocytic leukemia (CLL) transformation to more aggressive cytologic or histologic forms (prolymphocytic leukemia, large cell lymphoma, Hodgkin's disease) and those affected with autoimmune hemolytic anemia
2. Presence of serious diseases that prevent chemotherapy treatments
3. Presence of psychiatric comorbidity
4. HIV infection
5. Other prior neoplasm
6. Do not have signed informed consent
7. Pregnant or at risk of pregnancy by inadequate contraceptive measures.
8. Patients diagnosed with chronic lymphocytic leukemia (CLL) transformation to more aggressive cytologic or histologic forms (prolymphocytic leukemia, large cell lymphoma, Hodgkin's disease) and those affected with autoimmune hemolytic anemia
Minimum Eligible Age
45 Years
Maximum Eligible Age
65 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
OTHER
Sponsor Role
lead
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Responsibility Role
SPONSOR
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
José Antonio Pérez-Simón, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
University of Salamanca
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Department of Propedeutic Oncology, Medical University of Gdansk
Gdansk, , Poland
Site Status
Clinical Hematology Department. ICO-Hospital Germans Trias i Pujol. Jose Carreras Research Institute
Badalona, Barcelona, Spain
Site Status
Hospital Clinic I Provincial
Barcelona, , Spain
Site Status
Santa Creu I Sant Pau Hospital
Barcelona, , Spain
Site Status
Hospital Universitario de Salamanca
Salamanca, , Spain
Site Status
Countries
Review the countries where the study has at least one active or historical site.
Poland
Spain
References
Explore related publications, articles, or registry entries linked to this study.
Kroger N, Shaw B, Iacobelli S, Zabelina T, Peggs K, Shimoni A, Nagler A, Binder T, Eiermann T, Madrigal A, Schwerdtfeger R, Kiehl M, Sayer HG, Beyer J, Bornhauser M, Ayuk F, Zander AR, Marks DI; Clinical Trial Committee of the British Society of Blood and Marrow Transplantation and the German Cooperative Transplant Group. Comparison between antithymocyte globulin and alemtuzumab and the possible impact of KIR-ligand mismatch after dose-reduced conditioning and unrelated stem cell transplantation in patients with multiple myeloma. Br J Haematol. 2005 Jun;129(5):631-43. doi: 10.1111/j.1365-2141.2005.05513.x.
Reference Type
BACKGROUND
Chen PM, Tzeng CH, Fan FS, Hsieh RK, Wei CH. Bone marrow transplantation in Taiwan: low incidence of acute GVHD in patients with hematologic malignancies and severe aplastic anemia. Bone Marrow Transplant. 1994 Jun;13(6):709-11.
Reference Type
BACKGROUND
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.
Reference Type
BACKGROUND
Sullivan KM, Shulman HM, Storb R, Weiden PL, Witherspoon RP, McDonald GB, Schubert MM, Atkinson K, Thomas ED. Chronic graft-versus-host disease in 52 patients: adverse natural course and successful treatment with combination immunosuppression. Blood. 1981 Feb;57(2):267-76.
Reference Type
BACKGROUND
Morris E, Thomson K, Craddock C, Mahendra P, Milligan D, Cook G, Smith GM, Parker A, Schey S, Chopra R, Hatton C, Tighe J, Hunter A, Peggs K, Linch D, Goldstone A, Mackinnon S. Outcomes after alemtuzumab-containing reduced-intensity allogeneic transplantation regimen for relapsed and refractory non-Hodgkin lymphoma. Blood. 2004 Dec 15;104(13):3865-71. doi: 10.1182/blood-2004-03-1105. Epub 2004 Aug 10.
Reference Type
BACKGROUND
Delgado J, Pillai S, Benjamin R, Caballero D, Martino R, Nathwani A, Lovell R, Thomson K, Perez-Simon JA, Sureda A, Kottaridis P, Vazquez L, Peggs K, Sierra J, Milligan D, Mackinnon S. The effect of in vivo T cell depletion with alemtuzumab on reduced-intensity allogeneic hematopoietic cell transplantation for chronic lymphocytic leukemia. Biol Blood Marrow Transplant. 2008 Nov;14(11):1288-97. doi: 10.1016/j.bbmt.2008.09.001.
Reference Type
BACKGROUND
Perez-Simon JA, Kottaridis PD, Martino R, Craddock C, Caballero D, Chopra R, Garcia-Conde J, Milligan DW, Schey S, Urbano-Ispizua A, Parker A, Leon A, Yong K, Sureda A, Hunter A, Sierra J, Goldstone AH, Linch DC, San Miguel JF, Mackinnon S; Spanish and United Kingdom Collaborative Groups for Nonmyeloablative Transplantation. Nonmyeloablative transplantation with or without alemtuzumab: comparison between 2 prospective studies in patients with lymphoproliferative disorders. Blood. 2002 Nov 1;100(9):3121-7. doi: 10.1182/blood-2002-03-0701.
Reference Type
BACKGROUND
Martino R, Caballero MD, Canals C, Simon JA, Solano C, Urbano-Ispizua A, Bargay J, Rayon C, Leon A, Sarra J, Odriozola J, Conde JG, Sierra J, San Miguel J; ALLOPBSCT Subcommittee of the Spanish Group for Haematopoietic Transplantation (GETH); Group GEL-TAMO. Allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning: results of a prospective multicentre study. Br J Haematol. 2001 Dec;115(3):653-9. doi: 10.1046/j.1365-2141.2001.03153.x.
Reference Type
BACKGROUND
Schweighofer CD, Ritgen M, Eichhorst BF, Busch R, Abenhardt W, Kneba M, Hallek M, Wendtner CM. Consolidation with alemtuzumab improves progression-free survival in patients with chronic lymphocytic leukaemia (CLL) in first remission: long-term follow-up of a randomized phase III trial of the German CLL Study Group (GCLLSG). Br J Haematol. 2009 Jan;144(1):95-8. doi: 10.1111/j.1365-2141.2008.07394.x. Epub 2008 Oct 30.
Reference Type
BACKGROUND
Keating MJ, Flinn I, Jain V, Binet JL, Hillmen P, Byrd J, Albitar M, Brettman L, Santabarbara P, Wacker B, Rai KR. Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study. Blood. 2002 May 15;99(10):3554-61. doi: 10.1182/blood.v99.10.3554.
Reference Type
BACKGROUND
Rai KR, Freter CE, Mercier RJ, Cooper MR, Mitchell BS, Stadtmauer EA, Santabarbara P, Wacker B, Brettman L. Alemtuzumab in previously treated chronic lymphocytic leukemia patients who also had received fludarabine. J Clin Oncol. 2002 Sep 15;20(18):3891-7. doi: 10.1200/JCO.2002.06.119.
Reference Type
BACKGROUND
Osterborg A, Dyer MJ, Bunjes D, Pangalis GA, Bastion Y, Catovsky D, Mellstedt H. Phase II multicenter study of human CD52 antibody in previously treated chronic lymphocytic leukemia. European Study Group of CAMPATH-1H Treatment in Chronic Lymphocytic Leukemia. J Clin Oncol. 1997 Apr;15(4):1567-74. doi: 10.1200/JCO.1997.15.4.1567.
Reference Type
BACKGROUND
Chakrabarti S, Mackinnon S, Chopra R, Kottaridis PD, Peggs K, O'Gorman P, Chakraverty R, Marshall T, Osman H, Mahendra P, Craddock C, Waldmann H, Hale G, Fegan CD, Yong K, Goldstone AH, Linch DC, Milligan DW. High incidence of cytomegalovirus infection after nonmyeloablative stem cell transplantation: potential role of Campath-1H in delaying immune reconstitution. Blood. 2002 Jun 15;99(12):4357-63. doi: 10.1182/blood.v99.12.4357.
Reference Type
BACKGROUND
Hale G, Cobbold S, Novitzky N, Bunjes D, Willemze R, Prentice HG, Milligan D, MacKinnon S, Waldmann H; CAMPATH Users. CAMPATH-1 antibodies in stem-cell transplantation. Cytotherapy. 2001;3(3):145-64. doi: 10.1080/146532401753173981.
Reference Type
BACKGROUND
Kottaridis PD, Milligan DW, Chopra R, Chakraverty RK, Chakrabarti S, Robinson S, Peggs K, Verfuerth S, Pettengell R, Marsh JC, Schey S, Mahendra P, Morgan GJ, Hale G, Waldmann H, de Elvira MC, Williams CD, Devereux S, Linch DC, Goldstone AH, Mackinnon S. In vivo CAMPATH-1H prevents graft-versus-host disease following nonmyeloablative stem cell transplantation. Blood. 2000 Oct 1;96(7):2419-25.
Reference Type
BACKGROUND
Khouri IF, Przepiorka D, van Besien K, O'Brien S, Palmer JL, Lerner S, Mehra RC, Vriesendorp HM, Andersson BS, Giralt S, Korbling M, Keating MJ, Champlin RE. Allogeneic blood or marrow transplantation for chronic lymphocytic leukaemia: timing of transplantation and potential effect of fludarabine on acute graft-versus-host disease. Br J Haematol. 1997 May;97(2):466-73. doi: 10.1046/j.1365-2141.1997.272673.x.
Reference Type
BACKGROUND
Rondon G, Giralt S, Huh Y, Khouri I, Andersson B, Andreeff M, Champlin R. Graft-versus-leukemia effect after allogeneic bone marrow transplantation for chronic lymphocytic leukemia. Bone Marrow Transplant. 1996 Sep;18(3):669-72.
Reference Type
BACKGROUND
van Besien K, Sobocinski KA, Rowlings PA, Murphy SC, Armitage JO, Bishop MR, Chaekal OK, Gale RP, Klein JP, Lazarus HM, McCarthy PL Jr, Raemaekers JM, Reiffers J, Phillips GL, Schattenberg AV, Verdonck LF, Vose JM, Horowitz MM. Allogeneic bone marrow transplantation for low-grade lymphoma. Blood. 1998 Sep 1;92(5):1832-6.
Reference Type
BACKGROUND
Khouri IF, Keating M, Korbling M, Przepiorka D, Anderlini P, O'Brien S, Giralt S, Ippoliti C, von Wolff B, Gajewski J, Donato M, Claxton D, Ueno N, Andersson B, Gee A, Champlin R. Transplant-lite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment for lymphoid malignancies. J Clin Oncol. 1998 Aug;16(8):2817-24. doi: 10.1200/JCO.1998.16.8.2817.
Reference Type
BACKGROUND
Giralt S, Thall PF, Khouri I, Wang X, Braunschweig I, Ippolitti C, Claxton D, Donato M, Bruton J, Cohen A, Davis M, Andersson BS, Anderlini P, Gajewski J, Kornblau S, Andreeff M, Przepiorka D, Ueno NT, Molldrem J, Champlin R. Melphalan and purine analog-containing preparative regimens: reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation. Blood. 2001 Feb 1;97(3):631-7. doi: 10.1182/blood.v97.3.631.
Reference Type
BACKGROUND
Slavin S, Nagler A, Naparstek E, Kapelushnik Y, Aker M, Cividalli G, Varadi G, Kirschbaum M, Ackerstein A, Samuel S, Amar A, Brautbar C, Ben-Tal O, Eldor A, Or R. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood. 1998 Feb 1;91(3):756-63.
Reference Type
BACKGROUND
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
TIRCAMPATH-alo 2002
Identifier Type: -
Identifier Source: org_study_id