Tato stránka byla automaticky přeložena a přesnost překladu není zaručena. Podívejte se prosím na anglická verze pro zdrojový text.

Irradiated Donor Lymphocytes and Rituximab in Treating Patients With Relapsed or Refractory Lymphoproliferative Disease

A Pilot Study of Irradiated HLA-Partially Matched Allogeneic Related Donor Lymphocytes in Conjunction With Rituximab for Selected Patients With CD20 + Malignancies

RATIONALE: When irradiated lymphocytes from a donor are infused into the patient they may help the patient's immune system kill cancer cells. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving irradiated donor lymphocytes together with rituximab may kill more cancer cells.

PURPOSE: This clinical trial is studying the side effects and how well giving irradiated donor lymphocytes together with rituximab works in treating patients with relapsed or refractory lymphoproliferative disease.

Přehled studie

Detailní popis

OBJECTIVES:

Primary

  • Determine the toxicity of irradiated HLA-partially matched related donor lymphocytes when administered with rituximab in patients with relapsed or refractory CD20-positive lymphoproliferative disease.
  • Determine the efficacy of this regimen in these patients.

Secondary

  • Correlate response with Fc receptor FcγIIIA polymorphisms or predicted HLA-directed natural killer cell reactivity.

OUTLINE: This is a pilot study.

  • Rituximab therapy: Patients receive rituximab IV on days -1, 6, 13, and 20. Treatment repeats approximately every 4 months in the absence of disease progression or unacceptable toxicity.
  • Donor lymphocyte infusion: Patients receive irradiated donor lymphocytes IV over 1 hour on day 0. Treatment repeats every 8-16 weeks (alternating with courses of rituximab therapy) for up to 6 donor lymphocyte infusions in the absence of disease progression or unacceptable toxicity.

Peripheral blood is collected periodically during study for correlative laboratory studies. Blood samples are analyzed for FcγIIIA polymorphism by fluorescent in situ hybridization or by reverse transcriptase-polymerase chain reaction. Survival of donor lymphocytes is assessed by chimerism studies.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Typ studie

Intervenční

Zápis (Aktuální)

2

Fáze

  • Fáze 1

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní místa

    • New Jersey
      • New Brunswick, New Jersey, Spojené státy, 08903
        • Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

18 let a starší (Dospělý, Starší dospělý)

Přijímá zdravé dobrovolníky

Ne

Pohlaví způsobilá ke studiu

Všechno

Popis

DISEASE CHARACTERISTICS:

  • Histologically confirmed lymphoproliferative disease

    • CD20-positive disease
  • Bidimensionally measurable disease OR abnormal cells detected in blood
  • Resistant or refractory to standard therapies and/or unlikely to benefit from additional standard therapies* AND meets 1 of the following criteria:

    • Disease with anticipated response rate < 20% after treatment with rituximab alone, including any of the following:

      • Diffuse large cell lymphoma
      • B-cell lymphoblastic lymphoma
      • Burkitt's lymphoma
      • Acute lymphocytic leukemia
    • Relapsed or progressive disease after prior treatment with rituximab, including any of the following:

      • Hodgkin's lymphoma
      • Hairy cell leukemia
      • Chronic lymphocytic leukemia/small lymphocytic lymphoma meeting any of the following criteria:

        • Received prior fludarabine phosphate-containing regimens and relapsed within 1 year of treatment OR ineligible to receive such therapy due to comorbidities or allergies
        • Received prior anti-CD52 monoclonal antibody therapy and relapsed within 1 year of treatment OR ineligible to receive such therapy (for patients without symptomatic lymphadenopathy)
        • Has documentation of disease-associated symptoms, rapid disease progression, or other indications for treatment
      • B-cell prolymphocytic leukemia meeting any of the following criteria:

        • Received prior fludarabine phosphate- or alkylating agent-containing regimens and relapsed within 1 year of treatment OR ineligible to receive such therapy due to comorbidities or allergies
        • Received prior anti-CD52 monoclonal antibody therapy OR ineligible to receive such therapy (for patients without symptomatic lymphadenopathy)
      • Lymphoplasmacytic lymphoma, marginal zone lymphoma, mucosa-associated lymphoid tissue lymphoma, or follicular lymphoma meeting any of the following criteria:

        • Received prior fludarabine phosphate- and/or alkylating agent-containing regimens and relapsed within 1 year of treatment OR ineligible to receive such therapy due to comorbidities or allergies
        • Received prior anti-CD20 monoclonal antibody therapy and relapsed within 1 year of treatment OR ineligible to receive such therapy
        • Received prior radioconjugated anti-CD20 monoclonal antibody therapy OR ineligible to receive such therapy
        • Has documentation of disease-associated symptoms, rapid disease progression, or other indications for treatment
      • Multiple myeloma meeting any of the following criteria:

        • Received prior alkylating agent-, thalidomide-, corticosteroid-, or bortezomib-containing regimens and relapsed after 1 year of treatment OR ineligible to receive such therapies due to comorbidities or allergies
        • Received prior high-dose chemotherapy followed by autologous hematopoietic stem cell rescue and relapsed after treatment OR ineligible to receive such therapy
      • Mantle cell lymphoma meeting the following criteria:

        • Received prior combination chemotherapy and anti-CD20 monoclonal antibody therapy and relapsed after treatment OR ineligible to receive such therapy
      • Diffuse large B-cell lymphoma meeting any of the following criteria:

        • Received prior combination chemotherapy and relapsed after treatment OR ineligible to receive such therapy
        • Received prior salvage combination chemotherapy with or without high-dose chemotherapy followed by autologous hematopoietic stem cell rescue and relapsed after treatment OR not a candidate to receive such therapy
        • Received prior radiolabeled anti-CD20 monoclonal antibody therapy for transformed large cell lymphoma OR ineligible to receive such therapy
      • Burkitt's lymphoma meeting any of the following criteria:

        • Received prior combination chemotherapy and relapsed after treatment OR ineligible to receive such therapy
        • Received prior salvage combination chemotherapy with or without high-dose chemotherapy followed by autologous hematopoietic stem cell rescue and relapsed after treatment OR ineligible to receive such therapy
      • Lymphomatoid granulomatosis meeting any of the following criteria:

        • Received prior single-agent or combination chemotherapy and relapsed after treatment OR ineligible to receive such therapy
        • Has documentation of disease-associated symptoms, rapid disease progression, or other indications for treatment
      • Acute lymphocytic leukemia meeting any of the following criteria:

        • Received prior multi-agent combination chemotherapy administered in sequential induction, consolidation, and maintenance courses and relapsed during or after treatment OR ineligible to receive such therapy
        • Received prior chemotherapy with or without radiotherapy followed by allogeneic hematopoietic stem cell transplantation (HSCT) and relapsed after treatment OR not a candidate for such therapy
        • Received prior treatment with chemotherapy with or without radiotherapy followed by allogeneic HSCT and relapsed after treatment (or not a candidate for such therapy) AND demonstrates persistent cytogenetic, fluorescent in situ hybridization, or molecular (reverse transcriptase-polymerase chain reaction) evidence of the bcr-abl fusion gene despite 6 weeks of treatment with imatinib mesylate NOTE: *Not eligible to receive standard available salvage regimens anticipated to result in durable remission
  • No active CNS malignancy
  • Not considered a candidate for allogeneic HSCT
  • HLA-partially matched (≥ 2/6) related donor available

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • Life expectancy > 3 months
  • Not pregnant
  • Negative pregnancy test
  • Fertile women must use effective contraception
  • Bilirubin < 1.5 times upper limit of normal (ULN)
  • AST < 3.0 times ULN
  • Cardiac ejection fraction > 35%
  • Absolute neutrophil count > 1,000/mm³ (without cytokines)
  • Platelet count > 50,000/mm³ (untransfused)
  • No significant organ dysfunction
  • No active uncontrolled infections
  • No hypersensitivity reaction to rituximab that has precluded completion of a 4-week course of rituximab therapy
  • No uncontrolled psychiatric illness or medical condition that would preclude tolerance of study treatment

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Recovered from prior therapy for at least 7 days
  • More than 30 days since prior cytotoxic chemotherapy
  • At least 14 days since prior steroids
  • At least 14 days since prior radiotherapy to non-target lesions

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Léčba
  • Přidělení: N/A
  • Intervenční model: Přiřazení jedné skupiny
  • Maskování: Žádné (otevřený štítek)

Zbraně a zásahy

Skupina účastníků / Arm
Intervence / Léčba
Experimentální: Therapeutic allogeneic lymphocytes with rituximab
Patients will receive a single day infusion of standard dose rituximab (375 mg/m2) on days -1, 6, 13, 20 approximately every 4 months (in conjunction with alternating doses of the lymphocyte infusion).
The product will then be assigned to the specific patient and the released product will be transported to and administered to the patient at CINJ, after premedication of the patient with acetaminophen 650 mg PO and diphenhydramine- HCl 25 mg PO. Blood product administration will be every 8 weeks and undertaken according to CINJ standard procedures

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Časové okno
Toxicity as assessed by NCI CTCAE v3.0
Časové okno: 4 years
4 years

Sekundární výstupní opatření

Měření výsledku
Časové okno
Efficacy
Časové okno: 4 years
4 years

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia

1. ledna 2005

Primární dokončení (Aktuální)

1. února 2008

Dokončení studie (Aktuální)

1. února 2008

Termíny zápisu do studia

První předloženo

12. září 2005

První předloženo, které splnilo kritéria kontroly kvality

12. září 2005

První zveřejněno (Odhad)

15. září 2005

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Odhad)

17. září 2013

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

13. září 2013

Naposledy ověřeno

1. září 2013

Více informací

Termíny související s touto studií

Klíčová slova

Další identifikační čísla studie

  • CDR0000540171
  • P30CA072720 (Grant/smlouva NIH USA)
  • CINJ-010406 (Jiný identifikátor: Cancer Institute of New Jersey)

Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .

Klinické studie na rituximab

3
Předplatit