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Monoclonal Antibody Therapy in Treating Patients With Lymphoma or Colon Cancer That Has Not Responded to Vaccine Therapy

23 septembre 2016 mis à jour par: National Institutes of Health Clinical Center (CC)

A Pilot Study of Ipilimumab (MDX-CTLA4, MDX-010) in Lymphoma

RATIONALE: Monoclonal antibodies such as anti-cytotoxic T-lymphocyte-associated antigen-4 can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells.

PURPOSE: This phase II trial is studying anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody to see how well it works in treating patients with lymphoma or colon cancer that has not responded to vaccine therapy.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Description détaillée

OBJECTIVES:

Primary

  • Determine the toxicity of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody in patients with follicular or mantle cell lymphoma, colon cancer, or prostate cancer refractory to vaccine therapy. (part I) (prostate cancer and mantle cell lymphoma closed to accrual as of 3/10/2005; colon cancer closed to accrual as of 9/28/05)
  • Determine the toxicity of this drug at escalating doses in patients with follicular lymphoma. (part II)
  • Determine the toxicity of this drug at escalating doses in patients with non-Hodgkin's lymphoma or Hodgkin's lymphoma. (part III)

Secondary

  • Determine the ability of this drug to increase tumor-specific T-cell responses in these patients.
  • Determine the ability of this drug to produce clinical tumor response in these patients.
  • Determine the effect of this drug on suppressor T-cell populations (CD4+ and CD25+ cells) in these patients.

OUTLINE: This is a pilot, partial dose-escalation study.

  • Part I (patients with prostate or colon cancer or follicular or mantle cell lymphomas) (prostate cancer and mantle cell lymphoma closed to accrual as of 3/10/2005; colon cancer closed to accrual as of 9/28/05): Patients receive anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-CTLA4) IV over 90 minutes on day 1. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
  • Part II (dose-escalation) (patients with follicular lymphomas only): Patients receive MDX-CTLA4 as in part I. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of MDX-CTLA4 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

  • Part III (dose-escalation*) (patients with non-Hodgkin's or Hodgkin's lymphoma): Patients receive MDX-CTLA4 as in part II.

NOTE: No dose-escalation for lymphoma patients who have previously been treated with an allogeneic stem cell transplantation.

Patients are followed every other month.

PROJECTED ACCRUAL: A total of 89 patients will be accrued for this study.

Type d'étude

Interventionnel

Inscription (Réel)

89

Phase

  • La phase 1

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

    • Maryland
      • Bethesda, Maryland, États-Unis, 20892-1182
        • Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 120 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

DISEASE CHARACTERISTICS:

  • Histologically confirmed prostate cancer (closed to accrual as of 3/9/2005)

    • Prior therapy on protocol NCI-00-C-0137 or NCI-00-C-0154
    • Progressive disease (2 consecutively rising PSA levels, new bone scan lesion, or progression of soft tissue)
    • PSA at least 5 ng/mL
    • Progressive androgen-independent disease

      • Disease progression at least 4 weeks after flutamide withdrawal OR
      • Disease progression at least 6 weeks after bicalutamide or nilutamide withdrawal OR
  • Histologically confirmed follicular or mantle cell non-Hodgkin's lymphoma (mantle cell lymphoma closed to accrual as of 3/9/2005)

    • Prior therapy on protocol NCI-00-C-0133, NCI-01-C-0169, or NCI-00-C-0050
    • Progressive disease after standard treatment
    • Relapsed disease OR
  • Histologically confirmed colon cancer (colon cancer closed to accrual as of 9/28/05)

    • Prior therapy on protocol NCI-99-C-0023
    • Progressive disease OR
  • Histologically confirmed non-Hodgkin's lymphoma or Hodgkin's lymphoma

    • Progressive disease after standard treatment
    • No curative therapy exists
    • Prior allogeneic stem cell transplantation from a matched sibling or matched unrelated donor for an aggressive lymphoma allowed

      • Last infusion of allogeneic cells (either hematopoietic stem cells or donor lymphocytes) must have occurred > 90 days prior to study enrollment
  • No other standard therapy available or refused such therapy
  • No symptomatic or rapidly progressive malignancy requiring therapy
  • No symptomatic CNS metastases

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • Karnofsky 80-100%

Life expectancy

  • More than 2 months

Hematopoietic

  • WBC at least 2,500/mm^3
  • Granulocyte count at least 1,500/mm^3
  • Platelet count at least 50,000/mm^3
  • Hemoglobin at least 10 g/dL
  • Hematocrit at least 30%

Hepatic

  • Bilirubin no greater than 3.0 mg/dL (unless due to Gilbert's disease)
  • SGOT and SGPT no greater than 3 times upper limit of normal
  • Hepatitis B surface antigen negative
  • Hepatitis C antibody negative

Renal

  • Creatinine no greater than 2.0 mg/dL

Immunologic

  • HIV negative
  • Rheumatoid factor negative if history or evidence of arthritis
  • Anti-nuclear antibody (ANA) titer no greater than 1:80 if history or clinical signs or symptoms of connective tissue disease
  • No prior or active autoimmune disease (e.g., uveitis, rheumatoid arthritis, lupus erythematosus, autoimmune hemolytic anemia, ulcerative and hemorrhagic colitis, endocrine disorders [e.g., thyroiditis, hyperthyroidism, hypothyroidism, autoimmune hypophysitis/hypopituitarism, or adrenal insufficiency], sarcoid granuloma, myasthenia gravis, polymyositis,or Guillain-Barre syndrome)
  • No positive antibody titers to autoimmune diseases

    • Rheumatoid factor positive allowed unless ANA titer is greater than 1:80 and there is a history of or clinical signs or symptoms of connective tissue disease
  • No active infection

Other

  • No other active malignancy within the past 5 years except adequately treated squamous cell or basal cell skin cancer, carcinoma in situ of the cervix, or superficial bladder cancer
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 4 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • See Disease Characteristics
  • Recovered from prior vaccine therapy
  • No prior anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-CTLA4) for patients in part I of study

    • Patients in part II of study may have had up to 4 prior treatments with MDX-CTLA4
  • No concurrent vaccine therapy
  • No concurrent infliximab

Chemotherapy

  • At least 4 weeks since prior cytotoxic chemotherapy
  • No concurrent mercaptopurine, methotrexate, or cyclophosphamide

Endocrine therapy

  • See Disease Characteristics
  • At least 4 weeks since prior steroids
  • No concurrent systemic, inhaled, or topical steroids

Radiotherapy

  • At least 4 weeks since prior radiotherapy

Surgery

  • At least 4 weeks since prior major surgery

Other

  • Prior intervening therapy for prostate cancer, non-Hodgkin's lymphoma or colon cancer allowed
  • No other concurrent investigational therapy
  • No other concurrent immunosuppressants (e.g., cyclosporine or its analog)

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Masquage: Aucun (étiquette ouverte)

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Toxicity after every 3 courses of treatment and every month for up to a year after completion of study treatment

Mesures de résultats secondaires

Mesure des résultats
T-cell response after every 3 courses of treatment and every month for up to a year after completion of study treatment

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Les enquêteurs

  • Chaise d'étude: John E. Janik, MD, NCI - Metabolism Branch;MET

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 septembre 2002

Achèvement primaire (Réel)

1 septembre 2010

Achèvement de l'étude (Réel)

1 novembre 2010

Dates d'inscription aux études

Première soumission

3 octobre 2002

Première soumission répondant aux critères de contrôle qualité

26 janvier 2003

Première publication (Estimation)

27 janvier 2003

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Estimation)

26 septembre 2016

Dernière mise à jour soumise répondant aux critères de contrôle qualité

23 septembre 2016

Dernière vérification

1 mars 2012

Plus d'information

Termes liés à cette étude

Mots clés

Autres numéros d'identification d'étude

  • 020284
  • 02-C-0284
  • NCI-5744
  • CDR0000257563

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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