Activity & Safety Study of Lenalidomide & Rituximab as Non-chemotherapy Based Therapy on Chronic Lymphocytic Leukemia (LLC-LENAR-08)
Phase I Study of the Activity and Safety of Lenalidomide and Rituximab as Non-chemotherapy Therapy for Patients With Recurrent and Refractory Chronic Lymphocytic Leukemia
The rationale for combining lenalidomide with rituximab derives from preclinical observations suggesting that lenalidomide may enhance the ADCC (antigen-dependent cellular cytotoxicity) triggered by monoclonal antibodies such as rituximab. Lenalidomide augments NK cytotoxicity by increasing CD56dimCD3 subset, in addition to inducing IL-2 in T cells. These results provide the cellular and molecular basis for the use of lenalidomide as an adjuvant in immunotherapeutic strategies of monoclonal antibodies (mAb)-based therapies. The combination lenalidomide-rituximab was tested in lymphoma cell lines but not specifically on CLL cell lines. However the observed synergism was attributed to NK cells expansion, thus lending support to the notion that this synergism may operate in other B-cell lymphoproliferative malignancies.
The objective was to develop a non-cytotoxic and effective treatment for CLL that would fulfill an unmet medical need, as a significant proportion of CLL patients are elderly and frail. These patients experience an excess in chemotherapy induced toxicity, often preventing the completion of the planned treatment.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Type d'étude
Inscription (Réel)
Phase
- La phase 1
Contacts et emplacements
Lieux d'étude
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Córdoba, Espagne, 14004
- Hospital Universitario Reina Sofía
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Madrid, Espagne, 28046
- Hospital Universitario La Paz
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Madrid, Espagne, 28033
- MD Anderson Internacional España
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Salamanca, Espagne, 37007
- Hospital Clínico de Salamanca
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Sevilla, Espagne, 41013
- Hospital Virgen del Rocío
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Valencia, Espagne, 46010
- Hospital Clínico Universitario de Valencia
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Zaragoza, Espagne, 50009
- Hospital Universitario Miguel Servet
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
- Recurrent and refractory CLL patients that have received at least one previous treatment with purine analogs.
- Adequate liver function and renal function.
- ECOG performance status ≤ 2.
- Signed informed consent
- Male and female patients who are fertile agree to use an effective barrier method of birth control to avoid pregnancy.
Exclusion Criteria:
- Positive serological markers for hepatitis B with the exception of HBsAc in previously vaccinated patients
- Pregnant patients
- HIV infection
- Concurrent chemotherapy or immunotherapy
- Other malignancy within the last 2 years, except for localized cutaneous carcinoma
- Neurological impairment precluding understanding of protocol and the entailed visits and procedures.
- Patients with Renal insufficiency that requires dialysis.
Plan d'étude
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 |
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Expérimental: Lenalidomida, Rituximab
Phase I: Lenalidomide will be administered from day 1 to 21 of 28 days cycles, escalating doses (from 2,5mg to 25 mg).Rituximab dose will be administered at the standard (375 mg/m2 in the first cycle and 500 mg/m2 in successive cycles).
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Lenalidomide: Oral use. It will be administered from day 1 to 21 of 28 days cycles in a total of 6 cycles. Rituximab, intravenous use. The dose will be administered at the standard (375 mg/m2 in the first cycle and 500 mg/m2 in successive cycles). In the first cycle Rituximab will be administered in two divided doses:100mg/m2 total on day 1 and the rest up to 375mg/m2 on day 2. If lenalidomide treatment starts on day 1, Rituximab will be administered, in this first cycle, on days -2 (100 mg/m2) and -1 (275 mg/m2). In the second and subsequent cycles, 500 mg/m2 of Rituximab will be administered on day -1.
Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Phase I: To determine Starting Recommended Dose for the first cycle and the subsequent cycles (Maximal Tolerated Dose)in relapsed B-cell CLL patients.
Délai: 5 months
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6 treatment cycles followed by an evaluation visit (between 60-90 days after last dosing) and quarterly follow up visits, until disease progression.
Module I: patients on every cohort will have the same dose during treatment, except if they experiment DLT, in which case dose will be decreased (unless they are on the first dose level).
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5 months
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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To determine the toxicity profile of LenRtx.
Délai: 5 months
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Phase II: patients will be followed during 6 cycles, safety assessment visit and quarterly follow up visits
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5 months
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To determine the time to treatment failure.
Délai: 5 months
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Phase II: patients will be followed during 6 cycles, safety assessment visit and quarterly follow up visits
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5 months
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To determine the molecular response rate.
Délai: 5 months
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Phase II: patients will be followed during 6 cycles, safety assessment visit and quarterly follow up visits
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5 months
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To determine the clinical response rate (combined morphological and flow cytometry criteria).
Délai: 5 months
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6 treatment cycles followed by an evaluation visit (between 60-90 days after last dosing) and quarterly follow up visits, until disease progression
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5 months
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Collaborateurs et enquêteurs
Parrainer
Collaborateurs
Les enquêteurs
- Chercheur principal: José F Tomas, MD, MD Anderson Internacional España
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Maladies du système immunitaire
- Tumeurs par type histologique
- Tumeurs
- Troubles lymphoprolifératifs
- Maladies lymphatiques
- Troubles immunoprolifératifs
- Leucémie, cellule B
- Leucémie
- Leucémie lymphocytaire chronique à cellules B
- Leucémie, Lymphoïde
- Effets physiologiques des médicaments
- Agents antirhumatismaux
- Agents antinéoplasiques
- Facteurs immunologiques
- Agents antinéoplasiques immunologiques
- Inhibiteurs de l'angiogenèse
- Agents modulateurs de l'angiogenèse
- Substances de croissance
- Inhibiteurs de croissance
- Lénalidomide
- Rituximab
Autres numéros d'identification d'étude
- LLC-LENAR-08 (Autre identifiant: Fundación MD Anderson Internacional. España)
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