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Lenalidomide + Plerixafor in Previously Treated Chronic Lymphocytic Leukemia (CLL)

26 luglio 2017 aggiornato da: David Rizzieri, MD

Lenalidomide in Combination With Plerixafor in Patients With Previously Treated Chronic Lymphocytic Leukemia

In research studies, lenalidomide (also called Revlimid) has shown some response in chronic lymphocytic leukemia (CLL); however, responses are usually partial responses that occur after several months of taking the study drug. It is thought that by adding the drug plerixafor (also called Mozobil) responses may be improved and/or occur sooner.

The main purpose of this study is to determine the dose of plerixafor that is safe to use in combination with lenalidomide. The study will also look at the response rates of the combination of lenalidomide and plerixafor and the effect the study drugs have on CLL cells.

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Descrizione dettagliata

The combination of lenalidomide and plerixafor will be evaluated in this single institution, open label clinical study of subjects with relapsed chronic lymphocytic leukemia (CLL). The overall design of the phase 1 study includes up to three treatment "stages."

Each subject will receive lenalidomide 5mg by mouth daily beginning on cycle 1 day 1. If tolerated, the dose will be increased by 2.5mg every 7 days to a maximum dose of 10mg by mouth daily (Stage 1). Once the subject is stably maintained on a daily dose of lenalidomide of 10mg daily and the white blood cell (WBC) count is <100.0 x 109 / L, and has been taking lenalidomide for at least 28 days, plerixafor will be added (Stage 2). In the dose escalation phase, 4 different doses of plerixafor in combination with lenalidomide will be studied in cohorts of 3 to 6 subjects each, following a standard "3 + 3" format:

  • Cohort 1: plerixafor 0.24 mg/kg subcutaneous (SC) daily thrice weekly (Mon, Wed, Fri)
  • Cohort 2: plerixafor 0.32 mg/kg SC daily thrice weekly (Mon, Wed, Fri)
  • Cohort 3: plerixafor 0.42 mg/kg SC daily thrice weekly (Mon, Wed, Fri)
  • Cohort 4: plerixafor 0.54 mg/kg SC daily thrice weekly (Mon, Wed, Fri) Plerixafor will be administered for 3 weeks of each cycle (days 1, 3, 5, 8, 10, 12, 15, 17, and 19) followed by a 1 week rest period. Lenalidomide dosing will be continuous.

An interim assessment of response will be performed after 4 cycles of combination therapy:

  • Subjects achieving a complete response (CR) by National Cancer Institute (NCI)-96 criteria will continue lenalidomide monotherapy (plerixafor is discontinued) until disease progression.
  • Subjects achieving a partial response (PR) will continue both lenalidomide and plerixafor. Additionally, rituximab 375mg/m2 will be added on day 1 of each subsequent cycle beginning with cycle 5, day 1 of combination therapy. (Stage 3). Treatment with the combination of lenalidomide and plerixafor will continue for a maximum of 12 cycles of combination therapy. Subjects may receive up to 8 doses of rituximab concurrent with lenalidomide and plerixafor on day 1 of each cycle. Subjects will then continue single agent lenalidomide until disease progression.
  • Subjects with stable disease may continue lenalidomide and plerixafor at the discretion of the investigator and the subject. Rituximab 375 mg/m2 will be added on day 1 of each subsequent cycle. Treatment, dose, schedule, and duration are the same as for subjects achieving a PR.

Tipo di studio

Interventistico

Iscrizione (Effettivo)

21

Fase

  • Fase 1

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • Stati Uniti
    • North Carolina
      • Durham, North Carolina, Stati Uniti, 27710
        • Duke University Medical Center

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

18 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

Inclusion Criteria:

  • Histologically confirmed diagnosis of chronic lymphocytic leukemia (CLL) or Small lymphocytic lymphoma (SLL) as established by the National Cancer Institute (NCI) Working Group Response Criteria (NCI 96 Criteria).
  • Received one or more prior therapies for CLL.
  • Subjects must have symptomatic disease requiring therapy as defined by the protocol.
  • >/= 4 weeks from prior cancer therapy.
  • Eastern Cooperative Oncology Group (ECOG) performance status of </= 2.
  • All study subjects must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.

Exclusion Criteria:

  • Prolymphocytic leukemia (PLL).
  • Richter's (large cell) transformation.
  • Prior allogeneic transplant within 12 months or prior allogeneic transplant > 12 months currently receiving immunosuppressants.
  • Active autoimmune hemolytic anemia.
  • Central nervous system (CNS) involvement.
  • Chronic enteral corticosteroids > 10mg prednisone or equivalent.
  • Evidence of laboratory tumor lysis syndrome (TLS) by Cairo-Bishop Definition of Tumor Lysis Syndrome
  • Use of any other experimental drug or therapy within 28 days of baseline
  • Major surgery within 28 days of baseline.
  • Known hypersensitivity to thalidomide.
  • The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
  • Any prior use of lenalidomide.
  • Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV).

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: N / A
  • Modello interventistico: Assegnazione di gruppo singolo
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: Lenalidomide + Plerixafor+ Rituximab
  1. Lenalidomide 5mg by mouth (PO) daily beginning cycle 1 day 1.
  2. Stage 1: increase by 2.5mg every 7 days to a maximum dose of 10mg.
  3. Stage 2: plerixafor will be added after 28 days of 10mg dose maintenance and white blood cell count (WBC) <100.0 x 109 / L.

  4. Dose cohorts of escalating subcutaneous (SC) thrice weekly plerixafor with continuous 10mg lenalidomide:

    • Cohort 1: 0.24 mg/kg
    • Cohort 2: 0.32 mg/kg
    • Cohort 3: 0.42 mg/kg
    • Cohort 4: 0.54 mg/kg
  5. Stage 3: Rituximab 375mg/m2 will be added on day 1 of cycles 5-12, day 1 of combination therapy for subjects with PR.
  6. Subjects will then continue single agent lenalidomide until disease progression.
Droga: Lenalidomide + Plerixafor (+ Rituximab)
  1. Lenalidomide 5mg by mouth (PO) daily beginning cycle 1 day 1.
  2. Stage 1: increase by 2.5mg every 7 days to a maximum dose of 10mg.
  3. Stage 2: plerixafor will be added after 28 days of 10mg dose maintenance and white blood cell count (WBC) <100.0 x 109 / L.

  4. Dose cohorts of escalating subcutaneous (SC) thrice weekly plerixafor with continuous 10mg lenalidomide:

    • Cohort 1: 0.24 mg/kg
    • Cohort 2: 0.32 mg/kg
    • Cohort 3: 0.42 mg/kg
    • Cohort 4: 0.54 mg/kg
  5. Stage 3: Rituximab 375mg/m2 will be added on day 1 of cycles 5-12, day 1 of combination therapy for subjects with PR.
  6. Subjects will then continue single agent lenalidomide until disease progression.
Altri nomi:
  • Revimid
  • Rituxan
  • Mobile

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Lasso di tempo
Maximum Tolerated Dose
Lasso di tempo: 4-16 months
4-16 months

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Overall Response (Complete Response/Partial Response)
Lasso di tempo: at the end of 4 months of combination treatment and at 2 months after completion of therapy

NCI 96 Response Criteria

CR (Complete Response):

Lymphadenopathy = none > 1.5cm Hepatomegaly = none Splenomegaly = none Blood lymphocytes = <4000 per microliter Marrow = normocellular, <30% lymphocytes, no B-lymphoid nodules. Platelet count = >100,000 per microliter Hemoglobin = >11.0 grams per deciliter Neutrophils = >1500 per microliter

PR (Partial Response):

Lymphadenopathy = Decrease >/= 50% Hepatomegaly = Decrease >/= 50% Splenomegaly = Decrease >/= 50% Blood lymphocytes = Decrease >/= 50% from baseline Marrow = 50% reduction in marrow infiltrate or B-lymphoid nodules. Platelet count = >100,000 per microliter or increase >/= 50% over baseline Hemoglobin = >11.0 grams per deciliter or increase >/= 50% over baseline Neutrophils = >1500 per microliter or increase >/= 50% over baseline
at the end of 4 months of combination treatment and at 2 months after completion of therapy
Progression-free Survival (PFS)
Lasso di tempo: time from day 1 of treatment to disease progression, death, or 2 years, whichever comes first
time from day 1 of treatment to disease progression, death, or 2 years, whichever comes first
Overall Survival (OS)
Lasso di tempo: the time from day 1 of treatment to death or 2 years, whichever comes first
the time from day 1 of treatment to death or 2 years, whichever comes first
Reduction in Severity of B Symptoms
Lasso di tempo: at the end of stage 1 (lenalidomide alone), at the end of stage 2 (4 months of combination), and at 2 months post-completion of therapy
Reduction in the severity of the following B symptoms will be assessed: fever ≥ 101F, chills, night sweats, and anorexia with weight loss.
at the end of stage 1 (lenalidomide alone), at the end of stage 2 (4 months of combination), and at 2 months post-completion of therapy
Reduction in the Frequency of Blood and Platelet Transfusions
Lasso di tempo: 4 weeks prior to therapy and in the 4 weeks following the completion of therapy
The change in number of transfusions from pre- to post-treatment will be calculated and summarized across all patients by giving the minimum, the 25th, 50th (median) and the 75th percentile and the maximum.
4 weeks prior to therapy and in the 4 weeks following the completion of therapy

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

David Rizzieri, MD

Collaboratori

Genzyme, a Sanofi Company
Celgene Corporation

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

1 gennaio 2012

Completamento primario (Effettivo)

1 marzo 2014

Completamento dello studio (Effettivo)

1 marzo 2015

Date di iscrizione allo studio

Primo inviato

12 giugno 2011

Primo inviato che soddisfa i criteri di controllo qualità

13 giugno 2011

Primo Inserito (Stima)

14 giugno 2011

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

5 febbraio 2018

Ultimo aggiornamento inviato che soddisfa i criteri QC

26 luglio 2017

Ultimo verificato

1 luglio 2017

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • Pro00026715
  • RV0622 (Altro identificatore: Celgene)

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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