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Immunotherapy Using Lenalidomide + Bystander Vaccine in High Risk Myelodysplastic Syndrome (MDS)

10. Dezember 2019 aktualisiert von: H. Lee Moffitt Cancer Center and Research Institute

A Phase I Pilot Study of Immunotherapy Using Lenalidomide Plus "Bystander" Vaccine in Patients With High-Risk Myelodysplastic Syndrome (MDS)

The purpose of this study is to find out the maximum tolerated dose (MTD) of the combined therapy of lenalidomide (Revlimid®) and Granulocyte/macrophage colony stimulating factor and CD40 Ligand expressed in the K562 cell line (GM.CD40L) bystander vaccine. This research is also being done to see how well the combination of these drugs works to fight myelodysplastic syndrome (MDS).

Studienübersicht

Status

Abgeschlossen

Bedingungen

Detaillierte Beschreibung

Fixed dose of lenalidomide at 10 mg/day, Days 1- 21 of 28 days of treatment cycle, and 4 dose escalations of GM.CD40L vaccine: 10 X 10^6 GM.CDL cells per vaccination; 30 X 10^6 GM.CDL cells per vaccination; 60 X 10^6 GM.CDL cells per vaccination; 120 X 10^6 GM.CDL cells per vaccination; Vaccination at 2-week intervals, on days 8 and 22, for a total of four 28-day cycles.

Studientyp

Interventionell

Einschreibung (Tatsächlich)

22

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

    • Florida
      • Tampa, Florida, Vereinigte Staaten, 33612
        • H. Lee Moffitt Cancer Center & Research Institute

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 und älter (Erwachsene, Älterer Erwachsener)

Akzeptiert gesunde Freiwillige

Nein

Studienberechtigte Geschlechter

Alle

Beschreibung

Inclusion Criteria:

  • Must understand and voluntarily sign an informed consent form
  • Age ≥18 years at the time of signing the informed consent form
  • Able to comply with the study visit schedule and assessments required by the protocol
  • Documented diagnosis of MDS with subtypes of Refractory Anemia with Excess Blast 1 (RAEB-1) (myeloblast ≥5-9%) or Refractory Anemia with Excess Blast 2 (RAEB-2) (myeloblast ≥10-19%) or intermediate 2, Acute myelogenous leukemia with bone marrow myeloblast >30% and high risk defined by International Prognostic Scoring System (IPSS) scores or refractory anemia with excess blast in transformation (RAEB-t) (myeloblast ≥ 20-30%) as per French-American-British Classification System (FAB) criteria. Any single or combination of cytogenetic abnormalities is allowed.
  • Study treatment can be offered as first line treatment as long as the available food and Drug Administration (FDA) approved treatment options are explained by the treating physician and the participant declines such options.
  • Study treatment can be offered to patients who have failed, cannot tolerate or do not wish to continue other therapeutic agents for MDS.
  • Prior chemotherapy is allowed but should be off chemotherapy of any kind for at last 4 weeks prior to initiation of study therapy.
  • Must be able to provide adequate bone marrow (BM) aspirate and biopsy specimens for histopathological evaluation, cytogenetic analysis and tissue banking during the screening procedure.
  • Platelet count must be > 20,000/ µl without platelet transfusion.
  • Absolute neutrophil count (ANC) must be >500/ µl without myeloid growth factor support.
  • Should not be receiving erythropoietin and/or myeloid growth factor for at least 14 days prior to initiation of study therapy.
  • Should not have current diagnosis or prior history of any autoimmune or immune deficiency disorders including human immunodeficiency virus positive/acquired immunodeficiency syndrome (HIV+/AIDS).
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 14 days prior to and again within 24 hours of starting lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.
  • Both male and female and members of all races and ethnic groups are eligible for this study.

Exclusion Criteria:

  • Prior therapy with lenalidomide.
  • Proliferative chronic myelomonocytic leukemia (CMML with WBC≥12,000/µL in peripheral blood), confirmed by bone marrow biopsy.
  • Acute myelogenous leukemia with bone marrow myeloblast ≥30%
  • MDS secondary to treatment with radiotherapy, chemotherapy, and/or immunotherapy for malignant or autoimmune diseases are excluded.
  • Any of the following laboratory abnormalities:

    • Serum creatinine > 1.5 x upper limit of normal (ULN)
    • Serum aspartic transaminase (AST) or alanine transaminase (ALT) >2.0 x ULN
    • Serum total bilirubin > 2.0 mg/dL (34 µmol/L)
  • Prior ≥ grade-2 national Cancer Institute Common Toxicity Criteria (NCI CTC) allergic reaction to thalidomide.
  • Prior desquamating (blistering) rash while taking thalidomide.
  • Prior allergic reaction to vaccination of any sort.
  • Participants with ≥ grade-2 neuropathy.
  • Clinically significant anemia due to factors such as iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis or gastrointestinal bleeding.
  • Use of cytotoxic chemotherapeutic agents, growth factors, or experimental agents (agents that are not commercially available) for the treatment of MDS within 28 days of the start of drug treatment.
  • Prior history of malignancy other than MDS (except basal cell or squamous cell carcinoma or carcinoma in situ of the cervix) unless the participant has been free of disease for ≥3 years.
  • Any serious medical condition or psychiatric illness that will prevent the participant from signing the informed consent form or will place the participant at unacceptable risk if he/she participates in the study.
  • Pregnant or nursing females.
  • Use of corticosteroids greater than the equivalent of prednisone 10mg daily within 4 weeks of the first vaccination, and on-going need for corticosteroids greater than the equivalent of prednisone 10 mg daily

Studienplan

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

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: N / A
  • Interventionsmodell: Einzelgruppenzuweisung
  • Maskierung: Keine (Offenes Etikett)

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Experimental: Immunotherapy
Participants will take two 5 mg capsules of lenalidomide per day for 21 days followed by 7 days of rest. This 28 day period is considered 1 cycle. Participants will receive 4 treatment cycles with 28 days in each cycle. Those participants showing a clinical response after 4 cycles of treatment may continue to receive lenalidomide as a single agent for additional cycles at the treating Physicians discretion. During each 28 day cycle participants will also receive GM.CD40L bystander vaccination injections in 2-week intervals on days 8 and 22 for a total of 8 immunizations during the 4 cycle treatment period.
Patients will take 10 mg capsules of lenalidomide per day for 21 days followed by 7 days of rest. This 28 day period is considered 1 cycle. Patients will receive 4 treatment cycles with 28 days in each cycle.
Andere Namen:
  • Revlimid®
In addition to lenalidomide, during each 28 day cycle patients will also receive GM.CD40L bystander vaccination injections in 2-week intervals on days 8 and 22 for a total of 8 immunizations during the 4 cycle treatment period.
Andere Namen:
  • GM.CD40L

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Maximum Tolerated Dose (MTD)
Zeitfenster: 24 months
Determination of MTD of GM.CD40L bystander vaccine with lenalidomide in high-risk MDS patients.
24 months

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Number of Participants with Toxicities
Zeitfenster: 24 months
Determination of toxicities associated with combination of GM.CD40L bystander vaccine with lenalidomide in high-risk MDS patients.
24 months
Number of Participants with Augmentation of Specific T Cell Immunological Functions
Zeitfenster: 24 months
Augmentation of specific T cell immunological functions; T cell proliferation and Interferon-γ production, delayed type hypersensitivity (DTH) sensitivity by lenalidomide.
24 months
Number of Participants with Reduction of Bone Marrow Myeloblast
Zeitfenster: 24 months
Reduction of bone marrow myeloblast from baseline to post treatment with lenalidomide and GM.CD40L bystander vaccine.
24 months
Number of Participants with Improvement of Hemoglobin and/or red blood cell (RBC) Transfusion Independence
Zeitfenster: 24 months
Improvement of hemoglobin and/or RBC transfusion independence after combined immunotherapy treatment.
24 months
Number of Participants with Resolution of Karyotypic Changes
Zeitfenster: 24 months
Resolution of karyotypic changes after combined treatment.
24 months
Number of Participants with Augmentation of Other T Cell Parameters
Zeitfenster: 24 months
Augmentation of other T cell parameters after the combined treatment.
24 months
Duration of Response
Zeitfenster: 24 months
Determination of response duration evaluated by Wilms Tumor 1 (WT1) expression and clinical outcomes. Clinical response will be assessed using International Working Group (IWG) criteria.
24 months

Mitarbeiter und Ermittler

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

Mitarbeiter

Ermittler

  • Hauptermittler: Javier Pinilla, M.D., Ph.D., H. Lee Moffitt Cancer & Research Institute

Publikationen und hilfreiche Links

Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.

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 (Tatsächlich)

2. Februar 2009

Primärer Abschluss (Tatsächlich)

17. Februar 2014

Studienabschluss (Tatsächlich)

1. Dezember 2019

Studienanmeldedaten

Zuerst eingereicht

4. Februar 2009

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

10. Februar 2009

Zuerst gepostet (Schätzen)

11. Februar 2009

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

11. Dezember 2019

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

10. Dezember 2019

Zuletzt verifiziert

1. Dezember 2019

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Andere Studien-ID-Nummern

  • MCC-14998
  • 105861 (Andere Kennung: USF IRB)
  • RV-MDS-PI-202 (Andere Kennung: Celgene Corp.)
  • BB-IND 13478 (Andere Kennung: CBER)
  • 0803-907 (Andere Kennung: OBA)

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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