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

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).

Studieoversigt

Status

Afsluttet

Betingelser

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

22

Fase

  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

    • Florida
      • Tampa, Florida, Forenede Stater, 33612
        • H. Lee Moffitt Cancer Center & Research Institute

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: 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.
Andre navne:
  • 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.
Andre navne:
  • GM.CD40L

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Maximum Tolerated Dose (MTD)
Tidsramme: 24 months
Determination of MTD of GM.CD40L bystander vaccine with lenalidomide in high-risk MDS patients.
24 months

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Number of Participants with Toxicities
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 24 months
Improvement of hemoglobin and/or RBC transfusion independence after combined immunotherapy treatment.
24 months
Number of Participants with Resolution of Karyotypic Changes
Tidsramme: 24 months
Resolution of karyotypic changes after combined treatment.
24 months
Number of Participants with Augmentation of Other T Cell Parameters
Tidsramme: 24 months
Augmentation of other T cell parameters after the combined treatment.
24 months
Duration of Response
Tidsramme: 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

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Samarbejdspartnere

Efterforskere

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

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

2. februar 2009

Primær færdiggørelse (Faktiske)

17. februar 2014

Studieafslutning (Faktiske)

1. december 2019

Datoer for studieregistrering

Først indsendt

4. februar 2009

Først indsendt, der opfyldte QC-kriterier

10. februar 2009

Først opslået (Skøn)

11. februar 2009

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

11. december 2019

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

10. december 2019

Sidst verificeret

1. december 2019

Mere information

Begreber relateret til denne undersøgelse

Andre undersøgelses-id-numre

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

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

Kliniske forsøg med lenalidomide

Abonner