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Donor Stem Cell Transplant in Treating Patients With High-Risk Hematologic Cancer

28 ottobre 2013 aggiornato da: Northside Hospital, Inc.

Reduced Intensity Allogeneic Stem Cell Transplantation With Matched Unrelated Donors for Patients With Hematologic Malignancies

RATIONALE: Giving low doses of chemotherapy before a donor stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving a monoclonal antibody, such as alemtuzumab, before transplant and tacrolimus and methotrexate after transplant may stop this from happening.

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.

Panoramica dello studio

Descrizione dettagliata

OBJECTIVES:

  • 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.

Tipo di studio

Interventistico

Iscrizione (Effettivo)

36

Fase

  • Fase 2

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

    • Georgia
      • Atlanta, Georgia, Stati Uniti, 30342
        • Blood and Marrow Transplant Group of Georgia

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 40 anni a 72 anni (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

  • Diagnosis of one of the following hematological malignancies:

    • CML, with 1 of the following:

      • In first CP AND failed imatinib mesylate therapy, defined as failure to obtain a hematologic remission at 3 months or a major cytogenetic response (i.e., Ph+ cells < 35%) at 6 months or demonstrated clonal evolution or disease progression during therapy
      • In accelerated phase with < 15% blasts
      • In blast crisis that has entered into a second CP following induction chemotherapy
    • AML, with 1 of the following:

      • In second or subsequent complete remission (CR) (i.e., < 5% blasts by morphology, no residual leukemia by flow cytometry, and absence of cytogenetic abnormalities)
      • Failed primary induction chemotherapy, but subsequently entered into a CR with ≤ 2 subsequent re-induction chemotherapy treatment(s)
      • In first CR with intermediate-risk or poor-risk cytogenetics
    • ALL with 1 of the following:

      • In second or subsequent CR
      • In first CR AND presence of t(9;22)
    • MDS, with the following:

      • High-risk disease, defined by IPSS score of ≥ 1.5 at diagnosis AND meets 1 of the following criteria:

        • ≤ 10% blasts at diagnosis
        • In morphologic CR (< 5% blasts) following cytoreductive chemotherapy
    • CMML, with 1 of the following:

      • ≤ 10% blasts at diagnosis
      • In morphologic CR (< 5% blasts) following cytoreductive chemotherapy
    • CLL/PLL with the following:

      • Rai stage I-IV disease
      • Failed ≥ 1 prior chemotherapy regimen (including fludarabine phosphate) or ASCT
      • Documented chemosensitive or stable, non-bulky disease prior to transplant, defined as < 20% bone marrow involvement AND lymph node size < 3 cm in axial diameter
      • No bulky tumor masses, elevated lactate dehydrogenase (LDH), B symptoms, or progressive disease prior to transplant
    • Low-grade non-Hodgkin lymphoma (NHL) (i.e., small lymphocytic lymphoma, follicular center lymphoma [grade 1 or 2], marginal zone lymphoma, or B-cell lymphoma), with the following criteria:

      • Failed ≥ 1 prior chemotherapy regimen or ASCT
      • Documented chemosensitive or stable, non-bulky disease prior to transplant, defined as < 20% bone marrow involvement AND lymph node size < 3 cm in axial diameter
      • Received ≤ 3 prior chemotherapy regimens (monoclonal antibody therapy and involved-field radiotherapy are not considered a prior regimen)
      • No bulky tumor masses, elevated LDH, B symptoms, or progressive disease prior to transplant
    • Mantle cell lymphoma, with the following:

      • Failed to achieve remission or recurred after either conventional chemotherapy or ASCT
      • Responsive or stable disease to most recent prior therapy
      • No bulky tumor masses, elevated LDH, B symptoms, or progressive disease prior to transplant
    • Intermediate-grade NHL (i.e., follicular center lymphoma [grade 3] or diffuse large cell lymphoma), meeting the following criteria:

      • 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
    • Hodgkin lymphoma, with the following:

      • Relapsed after prior ASCT OR after ≥ 2 combination chemotherapy regimens and ineligible for 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
    • 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)

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: N / A
  • Modello interventistico: Assegnazione di gruppo singolo
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Altro: Hematopoietic Stem Cell Transplantation
All patients receive a hematopoietic stem cell transplant using one of two chemotherapy regimens based on donor type
43 mg subcutaneously over 3 days (3 mg on day -11, 10 mg on day -10, 30 mg on day -9)
Altri nomi:
  • Campath
curative potential of allogeneic transplant results from the immune anti-tumor effect of donor cells or GVT/GVL
in patients with Cd20+ malignancies: rituximab 375 mg/m*2 day -13. rituximab 1000 mg/m*2 on days, -6, +1, +8.
Altri nomi:
  • Rituxan
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.
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
Altri nomi:
  • Cytoxan
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.
Altri nomi:
  • Fludar
5 mg/m2 administered on days +1, +3 and +6
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
Altri nomi:
  • Prograf; FK506
Recipients will receive an allogeneic transplant on day 0 after receiving high-dose chemotherapy. This trial uses matched unrelated donor stem cells.
Altri nomi:
  • HSCT, allo transplant

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Survival at Day 100
Lasso di tempo: 100 day
Survival at Day 100
100 day

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Overall Survival at 1 Year
Lasso di tempo: 1 year
Evaluation of overall survival at 1 year (# of patients who are alive at 1 year post-transplant)
1 year
Non-relapse Mortality at Day 100
Lasso di tempo: Day 100
patients are evaluable for their cause of death at Day 100
Day 100
Non-relapse Mortality at 1 Year Post-transplant
Lasso di tempo: 1 year
Number of patients who died of non-relapse causes at one year. this is in clusive of all patients who were transplanted on study even though only 10 patients died at by 1 year time point. This outcome will be referenced in the donor chimerism outcome. Only 26/36 patients were eligible for this time point as that is all that were alive.
1 year
Complete Donor Chimerism
Lasso di tempo: 2 years
Complete donor chimerism (defined as >/= 95% donor cells in peripheral blood CD3+ and CD33+ was measured.
2 years
Neutrophil Recovery
Lasso di tempo: Day 100
The number of patients experiencing neutrophil recovery post transplant
Day 100
Platelet Engraftment
Lasso di tempo: Day 100
The number of patients experiencing platelet engraftment post-transplant
Day 100
Number of Patients Requiring the Use of Donor Leukocyte Infusion (DLI) for Early Mixed T-cell Chimerism
Lasso di tempo: Day 100
DLI is used for patients with mixed chimerism following transplant
Day 100
Number of Patients Experiencing Grade 2-4 Acute Graft-versus-host Disease Post-transplant
Lasso di tempo: patients were followed for 2 years
patients experiencing acute graft versus host disease post-transplant
patients were followed for 2 years
Number of Patients Experiencing Chronic Graft Versus Host Disease
Lasso di tempo: >100 days post-transplant
>100 days post-transplant
Number of Patients Experiencing Veno-occlusive Disease (VOD) Post-transplant
Lasso di tempo: 4 years
Patients will be evaluated up to 4 years post transplant
4 years

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Investigatori

  • Investigatore principale: Scott R. Solomon, MD, Blood and Marrow Transplant Group of Georgia

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

1 maggio 2005

Completamento primario (Effettivo)

1 marzo 2011

Completamento dello studio (Effettivo)

1 marzo 2012

Date di iscrizione allo studio

Primo inviato

7 gennaio 2009

Primo inviato che soddisfa i criteri di controllo qualità

7 gennaio 2009

Primo Inserito (Stima)

8 gennaio 2009

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Stima)

18 dicembre 2013

Ultimo aggiornamento inviato che soddisfa i criteri QC

28 ottobre 2013

Ultimo verificato

1 ottobre 2013

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Altri numeri di identificazione dello studio

  • CDR0000630617
  • BMTGG-NSH-756 (Altro identificatore: Northside Hospital, Inc)

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 .

Prove cliniche su alemtuzumab

3
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