- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica NCT00303719
Allogeneic Bone Marrow Transplantation Using Less Intensive Therapy
RATIONALE: A peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and radiation therapy, or that have become cancer. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclophosphamide and fludarabine together with total-body irradiation followed by cyclosporine and mycophenolate mofetil before the transplant may stop this from happening.
PURPOSE: This clinical trial is studying how well giving combination chemotherapy together with radiation therapy followed by cyclosporine and mycophenolate mofetil works in treating patients who are undergoing a donor stem cell transplant for hematologic cancer, metastatic breast cancer, or kidney cancer.
Panoramica dello studio
Stato
Condizioni
Descrizione dettagliata
OBJECTIVES:
- Determine if a nonmyeloablative regimen comprising cyclophosphamide, fludarabine, and radiotherapy followed by cyclosporine and mycophenolate mofetil provides a prompt and durable donor engraftment in patients with hematologic malignancies or kidney cancer who are undergoing allogeneic stem cell transplantation.
- Determine the safety of this nonmyeloablative transplantation regimen in these patients.
- Determine the risk of graft-versus-host-disease in patients treated with this regimen.
- Determine the antineoplastic potency of nonmyeloablative stem cell transplantation in patients treated with this regimen.
- Determine the effect of lower doses of daily fludarabine on treatment-related mortality (TRM) OUTLINE: Patients are stratified according to risk (standard vs high).
Preparative regimen*: Patients receive cyclophosphamide intravenously (IV) over 2 hours on day -6 and fludarabine IV over 1 hour on days -6 to -2. Patients undergo total body irradiation on day -1. Some patients also receive anti-thymocyte globulin (ATG)** IV every 12 hours on days -6 to -4. Patients who receive ATG* include the following:
- Related donor recipients who have not received combination chemotherapy within the past 6 months
- Unrelated donor recipients who have not received combination chemotherapy within the past 3 months
- Unrelated donor recipients who have received only 1 induction course for the treatment of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), or blastic phase chronic myelogenous leukemia (CML) NOTE: **Patients who underwent prior autologous stem cell transplantation in the past year do not receive ATG.
- Allogeneic peripheral blood stem cell transplantation (PBSCT): Patients undergo allogeneic PBSCT on day 0.
- Graft-versus-host-disease prophylaxis: Patients receive cyclosporine IV over 2 hours beginning on day -3 and continuing until at least day 100. Patients also receive mycophenolate mofetil IV or orally twice daily on days -3 to 30.
- Donor lymphocyte infusion (DLI): Patients without active GVHD but deteriorating donor chimerism may receive DLI IV over 2 hours.
After completion of study treatment, patients are followed periodically for 2 years.
PROJECTED ACCRUAL: A total of 300 patients will be accrued for this study.
Tipo di studio
Iscrizione (Effettivo)
Fase
- Fase 2
Contatti e Sedi
Luoghi di studio
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Minnesota
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Minneapolis, Minnesota, Stati Uniti, 55455
- Masonic Cancer Center, University of Minnesota
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
Inclusion Criteria:
Standard patients will be enrolled into Arms 1-6. High risk patients (transplant with aplasia) will be considered separately in Arm 7.
Age and Graft criteria (all patients)
- Patient's < or = 75 years old with a 5/6 or 6/6 related donor match are eligible.
- Patient's < or = 75 years who have a 7-8/8 HLA-A,B,C,DRB1 allele matched unrelated volunteer marrow and/or peripheral blood stem cell (PBSC) donor match are eligible.
Disease Criteria (standard risk patients)
- Acute myelogenous leukemia
- Acute lymphocytic leukemia
- Chronic myelogenous leukemia all types except blast crisis (note treated blast crisis in chronic phase is eligible).
- Non-Hodgkins lymphoma (NHL), Hodgkins, chronic lymphocytic leukemia, multiple myeloma demonstrating chemosensitive disease
- Acquired bone marrow failure syndromes
- Myelodysplastic syndrome of all subtypes including refractory anemia (RA) or all IPSS categories if severe pancytopenia, transfusion requirements not responsive to therapy, or high risk cytogenetics. Blasts must be less than 5%. If >5% requires therapy (induction or Hypomethylating agents) pre-transplant to decrease disease burden.
- Renal cell cancer,
- Chronic myeloproliferative disorder, i.e. myelofibrosis
Disease Criteria (High risk patients on Arm 7)
- Patients with refractory leukemia or MDS may be taken to transplant in aplasia after induction or re-induction chemotherapy or radiolabeled antibody. These high risk patients will be analyzed separately in Arm 7.
- Adequate organ function and performance status (all patients)
Exclusion Criteria:
- Pregnancy or breast feeding
- Evidence of HIV infection or known HIV positive serology
- Active serious infection
- Congenital bone marrow failure syndrome
- Previous irradiation that precludes the safe administration of an additional dose of 200 cGy of total body irradiation (TBI)
- Chronic myelogenous leukemia (CML) in refractory blast crisis
- Intermediate or high grade NHL, mantle cell NHL, and Hodgkins disease that is progressive on salvage therapy. Stable disease is acceptable to move forward provided it is non-bulky.
- Multiple Myeloma progressive on salvage chemotherapy.
DONOR ELIGIBILITY
- Related will undergo apheresis - if donor is unable to undergo apheresis, a bone marrow harvest is acceptable; unrelated volunteer donors must be able to undergo bone marrow harvest or apheresis.
- All donors must be able to give informed consent.
- Donors weighing less than 40 kg (children) will need evaluation by a pediatrician for suitability of the apheresis procedure. Informed consent must be obtained from parent or guardian as applicable for minors.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Non randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
---|---|
Sperimentale: High Risk Patients
Nonmyeloablative conditioning using fludarabine, cyclophosphamide and low dose Total Body Irradiation with or without anti-thymocyte globulin followed by allogeneic hematopoietic stem cell transplantation, immunosuppressive cyclosporine and mycophenolate mofetil and post-transplant use of bone marrow-stimulating filgrastim.
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ATG dose is 15 mg/kg intravenous (IV) every 12 hours for 6 doses on days -6, -5, and -4. Those that should/will receive ATG in the preparative regimen:
Altri nomi:
Cyclophosphamide will be given in a two hour infusion, total dose 50 mg/kg on day -6.
Altri nomi:
Patients will receive cyclosporine A (CSA) therapy beginning on day -3 maintaining a level of >200.
For adults the initial dose will be 2.5 mg/kg IV over 2 hours every 12 hours.
For children < 40 kg the initial dose will be 2.5 mg/kg IV over 2 hours every 8 hours.
Patients will receive CSA until day +100.
Altri nomi:
Fludarabine 30 mg/m^2/day intravenous (IV) on day -6 through day -2., total dose 150 mg/m^2 for 5 days.
Altri nomi:
Mycophenolate mofetil (MMF) 1.5 gram twice a day (BID) or if < 50 kg will be given 15 mg/kg orally(po) BID,beginning on day -3, and discontinue at day +30 or 7 days after engraftment (3 consecutive days of absolute neutrophil count (ANC) > 0.5 x 109 /L).
Altri nomi:
On day 0, if related donor, stem cells are infused via central line.
If unrelated donor, marrow/PBSC is infused after arrival and processing on day 0.
Altri nomi:
The dose of TBI will be 200 cGy given in a single fraction on day -1.
Altri nomi:
Patients with white blood cell (WBC) counts < 2500 any time after stem cell infusion will be started on G-CSF support at Day +5 at a dose of 5 mcg/kg intravenously or subcutaneously (IV/SQ) daily rounded to vial size until absolute neutrophil count (ANC) > 2500 for 2 consecutive days.
Altri nomi:
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Sperimentale: Standard Risk Patients
Nonmyeloablative conditioning using fludarabine, cyclophosphamide and low dose Total Body Irradiation with or without anti-thymocyte globulin followed by allogeneic hematopoietic stem cell transplantation, immunosuppressive cyclosporine and mycophenolate mofetil and post-transplant use of bone marrow-stimulating filgrastim.
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ATG dose is 15 mg/kg intravenous (IV) every 12 hours for 6 doses on days -6, -5, and -4. Those that should/will receive ATG in the preparative regimen:
Altri nomi:
Cyclophosphamide will be given in a two hour infusion, total dose 50 mg/kg on day -6.
Altri nomi:
Patients will receive cyclosporine A (CSA) therapy beginning on day -3 maintaining a level of >200.
For adults the initial dose will be 2.5 mg/kg IV over 2 hours every 12 hours.
For children < 40 kg the initial dose will be 2.5 mg/kg IV over 2 hours every 8 hours.
Patients will receive CSA until day +100.
Altri nomi:
Fludarabine 30 mg/m^2/day intravenous (IV) on day -6 through day -2., total dose 150 mg/m^2 for 5 days.
Altri nomi:
Mycophenolate mofetil (MMF) 1.5 gram twice a day (BID) or if < 50 kg will be given 15 mg/kg orally(po) BID,beginning on day -3, and discontinue at day +30 or 7 days after engraftment (3 consecutive days of absolute neutrophil count (ANC) > 0.5 x 109 /L).
Altri nomi:
On day 0, if related donor, stem cells are infused via central line.
If unrelated donor, marrow/PBSC is infused after arrival and processing on day 0.
Altri nomi:
The dose of TBI will be 200 cGy given in a single fraction on day -1.
Altri nomi:
Patients with white blood cell (WBC) counts < 2500 any time after stem cell infusion will be started on G-CSF support at Day +5 at a dose of 5 mcg/kg intravenously or subcutaneously (IV/SQ) daily rounded to vial size until absolute neutrophil count (ANC) > 2500 for 2 consecutive days.
Altri nomi:
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Neutrophil and Donor Cell Engraftment
Lasso di tempo: Day 42 and Day 100
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Successful sustained engraftment is defined as primary neutrophil engraftment by day 42 and e90% donor cells at day 100, with or without DLI. Engraftment based on absolute neutrophil count of donor origin > 0.5 x 10e9 /L for 3 days by day 42 |
Day 42 and Day 100
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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
Sopravvivenza globale
Lasso di tempo: 1 anno
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1 anno
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Serious Adverse Events
Lasso di tempo: Day 100
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Safety by development of severe adverse events within 100 days of transplant
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Day 100
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Transplant Related Mortality
Lasso di tempo: Day 100
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> 30% transplant related mortality at 100 days (non-relapse).
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Day 100
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Acute Graft-Versus-Host Disease
Lasso di tempo: Day 100
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Grade III-IV graft versus host disease
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Day 100
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Collaboratori e investigatori
Investigatori
- Investigatore principale: Erica Warlick, MD, Masonic Cancer Center, University of Minnesota
Pubblicazioni e link utili
Pubblicazioni generali
- Bachanova V, Burke MJ, Yohe S, Cao Q, Sandhu K, Singleton TP, Brunstein CG, Wagner JE, Verneris MR, Weisdorf DJ. Unrelated cord blood transplantation in adult and pediatric acute lymphoblastic leukemia: effect of minimal residual disease on relapse and survival. Biol Blood Marrow Transplant. 2012 Jun;18(6):963-8. doi: 10.1016/j.bbmt.2012.02.012. Epub 2012 Mar 16.
- Bachanova V, Sandhu K, Yohe S, Cao Q, Burke MJ, Verneris MR, Weisdorf D. Allogeneic hematopoietic stem cell transplantation overcomes the adverse prognostic impact of CD20 expression in acute lymphoblastic leukemia. Blood. 2011 May 12;117(19):5261-3. doi: 10.1182/blood-2011-01-329573. Epub 2011 Mar 14.
- Bachanova V, Verneris MR, DeFor T, Brunstein CG, Weisdorf DJ. Prolonged survival in adults with acute lymphoblastic leukemia after reduced-intensity conditioning with cord blood or sibling donor transplantation. Blood. 2009 Mar 26;113(13):2902-5. doi: 10.1182/blood-2008-10-184093. Epub 2009 Jan 28.
- Warlick E, Ahn KW, Pedersen TL, Artz A, de Lima M, Pulsipher M, Akpek G, Aljurf M, Cahn JY, Cairo M, Chen YB, Cooper B, Deol A, Giralt S, Gupta V, Khoury HJ, Kohrt H, Lazarus HM, Lewis I, Olsson R, Pidala J, Savani BN, Seftel M, Socie G, Tallman M, Ustun C, Vij R, Vindelov L, Weisdorf D. Reduced intensity conditioning is superior to nonmyeloablative conditioning for older chronic myelogenous leukemia patients undergoing hematopoietic cell transplant during the tyrosine kinase inhibitor era. Blood. 2012 Apr 26;119(17):4083-90. doi: 10.1182/blood-2012-02-409763. Epub 2012 Mar 9.
- Warlick ED, DeFor TE, Bejanyan N, Holtan S, MacMillan M, Blazar BR, Dusenbery K, Arora M, Bachanova V, Cooley S, Lazaryan A, McGlave P, Miller JS, Rashidi A, Slungaard A, Vercellotti G, Ustun C, Brunsein C, Weisdorf D. Reduced-Intensity Conditioning Followed by Related and Unrelated Allografts for Hematologic Malignancies: Expanded Analysis and Long-Term Follow-Up. Biol Blood Marrow Transplant. 2019 Jan;25(1):56-62. doi: 10.1016/j.bbmt.2018.07.038. Epub 2018 Aug 1.
Collegamenti utili
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
- Malattia cardiovascolare
- Malattie vascolari
- Malattie del sistema immunitario
- Neoplasie per tipo istologico
- Neoplasie
- Malattie linfoproliferative
- Disturbi immunoproliferativi
- Neoplasie urologiche
- Neoplasie urogenitali
- Neoplasie per sede
- Malattie renali
- Malattie urologiche
- Malattie del midollo osseo
- Malattie ematologiche
- Disturbi emorragici
- Disturbi emostatici
- Paraproteinemie
- Disturbi delle proteine del sangue
- Neoplasie renali
- Sindromi mielodisplastiche
- Mieloma multiplo
- Neoplasie, plasmacellule
- Plasmocitoma
- Effetti fisiologici delle droghe
- Meccanismi molecolari dell'azione farmacologica
- Agenti antinfettivi
- Inibitori enzimatici
- Agenti antireumatici
- Agenti antineoplastici
- Agenti immunosoppressivi
- Fattori immunologici
- Agenti Antineoplastici, Alchilanti
- Agenti Alchilanti
- Agonisti mieloablativi
- Agenti dermatologici
- Agenti antibatterici
- Antibiotici, Antineoplastici
- Agenti antimicotici
- Agenti antitubercolari
- Antibiotici, Antitubercolari
- Inibitori della calcineurina
- Ciclofosfamide
- Fludarabina
- Acido micofenolico
- Siero antilinfocitario
- Ciclosporina
- Ciclosporine
Altri numeri di identificazione dello studio
- 2001LS058
- UMN-MT2001-10 (Altro identificatore: Blood and Marrow Transplantation Program)
- 0108M06725 (Altro identificatore: IRB, University of Minnesota)
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .
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