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

23. September 2016 aktualisiert von: 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.

Studienübersicht

Status

Abgeschlossen

Bedingungen

Intervention / Behandlung

Detaillierte Beschreibung

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.

Studientyp

Interventionell

Einschreibung (Tatsächlich)

89

Phase

  • Phase 1

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienorte

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

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

18 Jahre bis 120 Jahre (Erwachsene, Älterer Erwachsener)

Akzeptiert gesunde Freiwillige

Nein

Studienberechtigte Geschlechter

Alle

Beschreibung

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)

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Maskierung: Keine (Offenes Etikett)

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Toxicity after every 3 courses of treatment and every month for up to a year after completion of study treatment

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
T-cell response after every 3 courses of treatment and every month for up to a year after completion of study treatment

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Ermittler

  • Studienstuhl: John E. Janik, MD, NCI - Metabolism Branch;MET

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn

1. September 2002

Primärer Abschluss (Tatsächlich)

1. September 2010

Studienabschluss (Tatsächlich)

1. November 2010

Studienanmeldedaten

Zuerst eingereicht

3. Oktober 2002

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

26. Januar 2003

Zuerst gepostet (Schätzen)

27. Januar 2003

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Schätzen)

26. September 2016

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

23. September 2016

Zuletzt verifiziert

1. März 2012

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Schlüsselwörter

Andere Studien-ID-Nummern

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

Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .

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