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

10 décembre 2019 mis à jour par: 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).

Aperçu de l'étude

Statut

Complété

Les conditions

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Réel)

22

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

    • Florida
      • Tampa, Florida, États-Unis, 33612
        • H. Lee Moffitt Cancer Center & Research Institute

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 et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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

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
  • Répartition: N / A
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: 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.
Autres noms:
  • 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.
Autres noms:
  • GM.CD40L

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Maximum Tolerated Dose (MTD)
Délai: 24 months
Determination of MTD of GM.CD40L bystander vaccine with lenalidomide in high-risk MDS patients.
24 months

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Number of Participants with Toxicities
Délai: 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
Délai: 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
Délai: 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
Délai: 24 months
Improvement of hemoglobin and/or RBC transfusion independence after combined immunotherapy treatment.
24 months
Number of Participants with Resolution of Karyotypic Changes
Délai: 24 months
Resolution of karyotypic changes after combined treatment.
24 months
Number of Participants with Augmentation of Other T Cell Parameters
Délai: 24 months
Augmentation of other T cell parameters after the combined treatment.
24 months
Duration of Response
Délai: 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

Collaborateurs et enquêteurs

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

Collaborateurs

Les enquêteurs

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

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

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 (Réel)

2 février 2009

Achèvement primaire (Réel)

17 février 2014

Achèvement de l'étude (Réel)

1 décembre 2019

Dates d'inscription aux études

Première soumission

4 février 2009

Première soumission répondant aux critères de contrôle qualité

10 février 2009

Première publication (Estimation)

11 février 2009

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

11 décembre 2019

Dernière mise à jour soumise répondant aux critères de contrôle qualité

10 décembre 2019

Dernière vérification

1 décembre 2019

Plus d'information

Termes liés à cette étude

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 .

Essais cliniques sur Leucémie

Essais cliniques sur lenalidomide

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