Donor Stem Cell Transplant in Treating Patients With High-Risk Hematologic Cancer
NCT ID: NCT00818961
Last Updated: 2013-12-18
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
TERMINATED
PHASE2
36 participants
INTERVENTIONAL
2005-05-31
2012-03-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
PURPOSE: This phase II trial is studying the side effects of donor stem cell transplant and to see how well it works in treating patients with high-risk hematologic cancer.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
* To evaluate the safety and toxicity of a reduced-intensity conditioning regimen followed by allogeneic bone marrow or peripheral blood stem cell transplantation from an HLA-matched unrelated donor in patients with high-risk hematologic malignancies.
* To evaluate engraftment by peripheral blood chimerism analysis.
* To determine the incidence and severity of acute and chronic graft-versus-host disease following the transplant.
* To examine the possibility of controlling hematologic malignancies by induction of a graft-versus-leukemia/tumor effect.
* To determine the disease-free survival, relapse, transplant-related mortality, and death from all causes.
OUTLINE:
* Reduced-intensity conditioning regimen: Patients receive 1 of 2 conditioning regimens according to diagnosis.
* Regimen 1 (acute leukemia, myelodysplastic syndromes, myeloproliferative syndrome, or chronic myelogenous leukemia): Patients receive fludarabine phosphate IV over 30 minutes and busulfan IV over 3 hours on days -6 to -3 or orally 4 times daily on days -7 to -3.
* Regimen 2 (lymphoproliferative malignancies): Patients receive fludarabine phosphate IV over 30 minutes and cyclophosphamide IV over 1 hour on days -5 to -3. Patients with CD20+ malignancies also receive rituximab IV over 4-6 hours on days -13, -6, 1, and 8.
* Transplantation: Patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on day 0.
* Graft-versus-host disease (GVHD) prophylaxis: Patients receive low-dose alemtuzumab subcutaneously on days -11 to -9 and tacrolimus IV over 24 hours beginning on day -3 and then orally twice daily beginning on day 14 and continuing until day 60, followed by a taper until day 180 in the absence of clinically significant GVHD. Patients also receive methotrexate on days 1, 3, and 6.
Patients who exhibit persistent mixed chimerism or disease relapse/progression despite full withdrawal of immunosuppression may receive up to 3 donor lymphocyte infusions.
Blood samples are taken on days 30, 60, and 100 and then every 4 weeks thereafter for chimerism studies by PCR analysis.
After completion of study therapy, patients are followed periodically for up to 60 months.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Hematopoietic Stem Cell Transplantation
All patients receive a hematopoietic stem cell transplant using one of two chemotherapy regimens based on donor type
alemtuzumab
43 mg subcutaneously over 3 days (3 mg on day -11, 10 mg on day -10, 30 mg on day -9)
graft-versus-tumor induction therapy
curative potential of allogeneic transplant results from the immune anti-tumor effect of donor cells or GVT/GVL
rituximab
in patients with Cd20+ malignancies: rituximab 375 mg/m\*2 day -13. rituximab 1000 mg/m\*2 on days, -6, +1, +8.
busulfan
For patients with AML, CML, MDS, MPS and ALL only: IV or oral busulfan may be given IV busulfan: 130 mg/m2 over 3 hours once daily on days -6, -5, -4 and -3 Oral busulfan: taken every 6 hours x 15 doses beginning on day -7 at 6pm and continuing through day -3 at 6am. 1 mg/kg test dose will be given prior to day -7 and PK samples will be drawn to calculate AUC.
cyclophosphamide
750 mg/m2 infused over 1 hour once daily on days -5, -4 and -3. Cyclophosphamide will be started approximately 4 hours after the start of Fludarabine
fludarabine phosphate
For patients with CLL, NHL \& HD: 30 mg/m2 infused over 30 minutes once daily on days -5, -4 and -3 For patients with AML, CML, MDS, MPS and ALL: 40 mg/m2 infused over 30 minutes once daily on days -6, -5, -4 and -3.
methotrexate
5 mg/m2 administered on days +1, +3 and +6
tacrolimus
0.03mg/kg/day infused over 24 hours starting on day -1 and switched to oral (twice daily divided dose) on day 14 or when able to tolerate PO
allogeneic bone marrow transplantation
Recipients will receive an allogeneic transplant on day 0 after receiving high-dose chemotherapy. This trial uses matched unrelated donor stem cells.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
alemtuzumab
43 mg subcutaneously over 3 days (3 mg on day -11, 10 mg on day -10, 30 mg on day -9)
graft-versus-tumor induction therapy
curative potential of allogeneic transplant results from the immune anti-tumor effect of donor cells or GVT/GVL
rituximab
in patients with Cd20+ malignancies: rituximab 375 mg/m\*2 day -13. rituximab 1000 mg/m\*2 on days, -6, +1, +8.
busulfan
For patients with AML, CML, MDS, MPS and ALL only: IV or oral busulfan may be given IV busulfan: 130 mg/m2 over 3 hours once daily on days -6, -5, -4 and -3 Oral busulfan: taken every 6 hours x 15 doses beginning on day -7 at 6pm and continuing through day -3 at 6am. 1 mg/kg test dose will be given prior to day -7 and PK samples will be drawn to calculate AUC.
cyclophosphamide
750 mg/m2 infused over 1 hour once daily on days -5, -4 and -3. Cyclophosphamide will be started approximately 4 hours after the start of Fludarabine
fludarabine phosphate
For patients with CLL, NHL \& HD: 30 mg/m2 infused over 30 minutes once daily on days -5, -4 and -3 For patients with AML, CML, MDS, MPS and ALL: 40 mg/m2 infused over 30 minutes once daily on days -6, -5, -4 and -3.
methotrexate
5 mg/m2 administered on days +1, +3 and +6
tacrolimus
0.03mg/kg/day infused over 24 hours starting on day -1 and switched to oral (twice daily divided dose) on day 14 or when able to tolerate PO
allogeneic bone marrow transplantation
Recipients will receive an allogeneic transplant on day 0 after receiving high-dose chemotherapy. This trial uses matched unrelated donor stem cells.
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* No bulky tumor masses, elevated LDH, B symptoms, or progressive disease prior to transplant
* Peripheral T-cell NHL, with the following:
* Failed to achieve remission or recurred after either conventional chemotherapy or ASCT
* Documented chemosensitive, non-bulky disease prior to transplant, defined as at least a partial remission to salvage chemotherapy (≥ 50% reduction in diameter of all disease sites)
* No bulky tumor masses, elevated LDH, B symptoms, or progressive disease prior to transplant
* Myeloproliferative syndrome with poor risk features, meeting 1 of the following criteria:
* \< 55 years old AND Lille score of 1
* Lille score of 2
* HgB \< 10 g/dL AND abnormal karyotype
* High-risk disease, with 1 of the following:
* Age 40-72 years
* Any age AND deemed to be at significantly increased risk of morbidity and death following a standard, myeloablative unrelated donor stem cell transplant (e.g., received extensive prior therapy, including ASCT)
* HLA-matched unrelated donor available, with 1 of the following:
* 8/8 match at HLA-A, B, C, or DR loci by high-resolution genotyping
* Single allelic mismatch at either the HLA-B or HLA-C loci donor by high-resolution molecular typing
* No single allelic mismatch at HLA-A or HLA-DR loci
* KPS 80-100%
* Adapted weighted Charlson Comorbidity Index \< 3
* Serum creatinine ≤ 2.0 mg/dL
* AST or ALT \< 3 times upper limit of normal (ULN)
* Total bilirubin \< 1.5 times ULN
* LVEF ≥ 45%
* DLCO \> 50%
* No hypoxia at rest with oxygen saturation \< 92% on room air (corrected with bronchodilator therapy)
* No other severe pulmonary function abnormalities
* No HIV infection
* No active hepatitis B or C infection that, in the opinion of a gastroenterologist or the transplant committee, places the patient at moderate to high risk for developing severe hepatic disease
* No active opportunistic infection (e.g., fungal pneumonia, tuberculosis, or viral infection)
40 Years
72 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Blood and Marrow Transplant Group of Georgia
OTHER
Northside Hospital, Inc.
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Scott R. Solomon, MD
Role: PRINCIPAL_INVESTIGATOR
Blood and Marrow Transplant Group of Georgia
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Blood and Marrow Transplant Group of Georgia
Atlanta, Georgia, United States
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
McGlave PB, Shu XO, Wen W, Anasetti C, Nademanee A, Champlin R, Antin JH, Kernan NA, King R, Weisdorf DJ. Unrelated donor marrow transplantation for chronic myelogenous leukemia: 9 years' experience of the national marrow donor program. Blood. 2000 Apr 1;95(7):2219-25.
Sierra J, Storer B, Hansen JA, Martin PJ, Petersdorf EW, Woolfrey A, Matthews D, Sanders JE, Storb R, Appelbaum FR, Anasetti C. Unrelated donor marrow transplantation for acute myeloid leukemia: an update of the Seattle experience. Bone Marrow Transplant. 2000 Aug;26(4):397-404. doi: 10.1038/sj.bmt.1702519.
Weisdorf DJ, Billett AL, Hannan P, Ritz J, Sallan SE, Steinbuch M, Ramsay NK. Autologous versus unrelated donor allogeneic marrow transplantation for acute lymphoblastic leukemia. Blood. 1997 Oct 15;90(8):2962-8.
Anderson JE, Anasetti C, Appelbaum FR, Schoch G, Gooley TA, Hansen JA, Buckner CD, Sanders JE, Sullivan KM, Storb R. Unrelated donor marrow transplantation for myelodysplasia (MDS) and MDS-related acute myeloid leukaemia. Br J Haematol. 1996 Apr;93(1):59-67. doi: 10.1046/j.1365-2141.1996.4811022.x.
Izutsu K, Kanda Y, Ohno H, Sao H, Ogawa H, Miyazaki Y, Kawa K, Kodera Y, Kato S, Morishima Y, Hirai H; Japan Marrow Donor Program. Unrelated bone marrow transplantation for non-Hodgkin lymphoma: a study from the Japan Marrow Donor Program. Blood. 2004 Mar 1;103(5):1955-60. doi: 10.1182/blood-2003-03-0937. Epub 2003 Nov 6.
Shaw BE, Peggs K, Bird JM, Cavenagh J, Hunter A, Alejandro Madrigal J, Russell NH, Sirohi B, Towlson K, Williams CD, Marks DI; Clinical Trials Committee of the British Society of Blood and Marrow Transplantation. The outcome of unrelated donor stem cell transplantation for patients with multiple myeloma. Br J Haematol. 2003 Dec;123(5):886-95. doi: 10.1046/j.1365-2141.2003.04714.x.
Davies SM, Kollman C, Anasetti C, Antin JH, Gajewski J, Casper JT, Nademanee A, Noreen H, King R, Confer D, Kernan NA. Engraftment and survival after unrelated-donor bone marrow transplantation: a report from the national marrow donor program. Blood. 2000 Dec 15;96(13):4096-102.
Hansen JA, Gooley TA, Martin PJ, Appelbaum F, Chauncey TR, Clift RA, Petersdorf EW, Radich J, Sanders JE, Storb RF, Sullivan KM, Anasetti C. Bone marrow transplants from unrelated donors for patients with chronic myeloid leukemia. N Engl J Med. 1998 Apr 2;338(14):962-8. doi: 10.1056/NEJM199804023381405.
Sorror ML, Maris MB, Storer B, Sandmaier BM, Diaconescu R, Flowers C, Maloney DG, Storb R. Comparing morbidity and mortality of HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative and myeloablative conditioning: influence of pretransplantation comorbidities. Blood. 2004 Aug 15;104(4):961-8. doi: 10.1182/blood-2004-02-0545. Epub 2004 Apr 27.
Sullivan KM, Weiden PL, Storb R, Witherspoon RP, Fefer A, Fisher L, Buckner CD, Anasetti C, Appelbaum FR, Badger C, et al. Influence of acute and chronic graft-versus-host disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukemia. Blood. 1989 May 1;73(6):1720-8.
Mehta J, Singhal S. Graft-versus-myeloma. Bone Marrow Transplant. 1998 Nov;22(9):835-43. doi: 10.1038/sj.bmt.1701459.
Jones RJ, Ambinder RF, Piantadosi S, Santos GW. Evidence of a graft-versus-lymphoma effect associated with allogeneic bone marrow transplantation. Blood. 1991 Feb 1;77(3):649-53.
Porter DL, Connors JM, Van Deerlin VM, Duffy KM, McGarigle C, Saidman SL, Leonard DG, Antin JH. Graft-versus-tumor induction with donor leukocyte infusions as primary therapy for patients with malignancies. J Clin Oncol. 1999 Apr;17(4):1234. doi: 10.1200/JCO.1999.17.4.1234.
O'Brien S, Kantarjian H, Beran M, Smith T, Koller C, Estey E, Robertson LE, Lerner S, Keating M. Results of fludarabine and prednisone therapy in 264 patients with chronic lymphocytic leukemia with multivariate analysis-derived prognostic model for response to treatment. Blood. 1993 Sep 15;82(6):1695-700.
Giralt S, Estey E, Albitar M, van Besien K, Rondon G, Anderlini P, O'Brien S, Khouri I, Gajewski J, Mehra R, Claxton D, Andersson B, Beran M, Przepiorka D, Koller C, Kornblau S, Korbling M, Keating M, Kantarjian H, Champlin R. Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. Blood. 1997 Jun 15;89(12):4531-6.
Diaconescu R, Flowers CR, Storer B, Sorror ML, Maris MB, Maloney DG, Sandmaier BM, Storb R. Morbidity and mortality with nonmyeloablative compared with myeloablative conditioning before hematopoietic cell transplantation from HLA-matched related donors. Blood. 2004 Sep 1;104(5):1550-8. doi: 10.1182/blood-2004-03-0804. Epub 2004 May 18.
Escalon MP, Champlin RE, Saliba RM, Acholonu SA, Hosing C, Fayad L, Giralt S, Ueno NT, Maadani F, Pro B, Donato M, McLaughlin P, Khouri IF. Nonmyeloablative allogeneic hematopoietic transplantation: a promising salvage therapy for patients with non-Hodgkin's lymphoma whose disease has failed a prior autologous transplantation. J Clin Oncol. 2004 Jun 15;22(12):2419-23. doi: 10.1200/JCO.2004.09.092.
Khouri IF, Lee MS, Saliba RM, Andersson B, Anderlini P, Couriel D, Hosing C, Giralt S, Korbling M, McMannis J, Keating MJ, Champlin RE. Nonablative allogeneic stem cell transplantation for chronic lymphocytic leukemia: impact of rituximab on immunomodulation and survival. Exp Hematol. 2004 Jan;32(1):28-35. doi: 10.1016/j.exphem.2003.09.021.
Kernan NA, Bartsch G, Ash RC, Beatty PG, Champlin R, Filipovich A, Gajewski J, Hansen JA, Henslee-Downey J, McCullough J, et al. Analysis of 462 transplantations from unrelated donors facilitated by the National Marrow Donor Program. N Engl J Med. 1993 Mar 4;328(9):593-602. doi: 10.1056/NEJM199303043280901.
Champlin RE, Passweg JR, Zhang MJ, Rowlings PA, Pelz CJ, Atkinson KA, Barrett AJ, Cahn JY, Drobyski WR, Gale RP, Goldman JM, Gratwohl A, Gordon-Smith EC, Henslee-Downey PJ, Herzig RH, Klein JP, Marmont AM, O'Reilly RJ, Ringden O, Slavin S, Sobocinski KA, Speck B, Weiner RS, Horowitz MM. T-cell depletion of bone marrow transplants for leukemia from donors other than HLA-identical siblings: advantage of T-cell antibodies with narrow specificities. Blood. 2000 Jun 15;95(12):3996-4003.
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.
Byrne JL, Stainer C, Cull G, Haynes AP, Bessell EM, Hale G, Waldmann H, Russell NH. The effect of the serotherapy regimen used and the marrow cell dose received on rejection, graft-versus-host disease and outcome following unrelated donor bone marrow transplantation for leukaemia. Bone Marrow Transplant. 2000 Feb;25(4):411-7. doi: 10.1038/sj.bmt.1702165.
Faulkner RD, Craddock C, Byrne JL, Mahendra P, Haynes AP, Prentice HG, Potter M, Pagliuca A, Ho A, Devereux S, McQuaker G, Mufti G, Yin JL, Russell NH. BEAM-alemtuzumab reduced-intensity allogeneic stem cell transplantation for lymphoproliferative diseases: GVHD, toxicity, and survival in 65 patients. Blood. 2004 Jan 15;103(2):428-34. doi: 10.1182/blood-2003-05-1406. Epub 2003 Sep 11.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
BMTGG-NSH-756
Identifier Type: OTHER
Identifier Source: secondary_id
CDR0000630617
Identifier Type: -
Identifier Source: org_study_id