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- Klinische proef NCT01744626
Safety Study of CC-292 and Rituximab in Subjects With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
A Phase 1b, Multi-center, Open Label, Study to Determine the Safety and Activity of CC-292 in Combination With Rituximab in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma.
Studie Overzicht
Toestand
Interventie / Behandeling
Gedetailleerde beschrijving
This dose finding study uses a 3 + 3 dose escalation and expansion design to establish the recommended Phase 2 dose (RP2D). Treatment will consist 28 day treatment cycles with a single Rituximab infusion per cycle for 6 cycles and twice daily (days 1-28) administration of CC-292 with a starting dose cohort of 375mg twice a day. Following safety review of the data from the initial cohort and confirmation that the initial dose is tolerable, the next dose level will be enrolled with a once per cycle Rituximab infusion for 6 cycles and twice daily CC-292 at 500 mg.
Determination of the maximum tolerated dose and/or optimal biologic effect will be used to establish a dose for evaluation in an expansion cohort of 24 subjects. Evaluation of the data for subjects in the expansion cohorts will result in establishment of a RP2D.
Studietype
Inschrijving (Werkelijk)
Fase
- Fase 1
Contacten en locaties
Studie Locaties
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Bayern, Duitsland, 80804
- Städt. Klinikum München-Schwabing
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Bayern, Duitsland, 907080
- Universitätsklinikum Würzburg
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Köln, Duitsland, 50924
- Universitätsklinik Köln
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Bayern
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Ulm, Bayern, Duitsland, 89070
- Universitätsklinik Ulm
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Alabama
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Huntsville, Alabama, Verenigde Staten, 35805
- Clearview Cancer Institute
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Indiana
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Lafayette, Indiana, Verenigde Staten, 47905
- Horizon Oncology Research, Inc
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New Jersey
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Hackensack, New Jersey, Verenigde Staten, 07601
- Hackensack UMC
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Tennessee
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Memphis, Tennessee, Verenigde Staten, 38120
- The West Clinic
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
Inclusion Criteria:
- Male and female subjects 18 years of age and older at the time of signing the informed consent document.
- Understand and voluntarily sign an informed consent document (ICD) prior to any study related assessments/procedures being conducted.
- Able to adhere to the study visit schedule and other protocol requirements.
- Body weight ≥ 50 kg.
- Must have a documented diagnosis of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) (International Workshop) guidelines for the diagnosis and treatment of CLL (Appendix A), or lymphoma guidelines (Appendix B) for diagnosis and treatment of SLL by investigator assessment.
Have failed ≥ 1 previous treatments for CLL/SLL, and have relapsed or refractory disease following last prior treatment.
- Refractory is defined as CLL/SLL that does not achieve at least a partial response (PR) to therapy or that progresses within 6 months of treatment. Relapsed CLL/SLL refers to disease that progresses after ≥ 6 months in subjects who had achieved a PR or complete response (CR) to therapy.
- Subjects must have failed, refused, be ineligible, or not otherwise appropriate, per the investigator's judgment, for autologous stem cell transplant (SCT) unless enrollment in this study is anticipated to debulk lesions in preparation for SCT.
- Eastern Cooperative Oncology Group performance status (ECOG PS) of ≤ 2
- Life expectancy of at least 3 months form the time of signing the ICD.
- Females of childbearing potential (FCBP)must have a negative medically supervised pregnancy test prior to starting of study therapy.
Male subjects must:
- Agree to use a condom during sexual contact with a FCBP, even if they have had a vasectomy, throughout study drug treatment, during any dose interruption and for 28 days after end of study therapy.
- Agree to not donate semen during study drug treatment and for 28 days after end of study drug treatment.
- Ability to swallow oral capsules without difficulty.
- Have an echocardiogram or multigated acquisition scan of the heart demonstrating left ventricular ejection fraction (LVEF) ≥ 50% or the institution's lower limit of normal.
- Have recovered from adverse, toxic effects of prior therapies to Grade ≤ 1 National Cancer Institute Common Terminology Criteria for Adverse Events (NCI/CTCAE) version 4.03 except for alopecia and peripheral neuropathy. This requirement will be subordinate to specific clinical and laboratory criteria that are otherwise specifically addressed in these inclusion/exclusion criteria.
Exclusion Criteria:
- Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
- Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
- Any condition that confounds the ability to interpret data from the study.
- Autologous stem cell transplant within 3 months of screening date.
Uncontrolled intercurrent illness including, but not limited to:
- Ongoing or active infection requiring parenteral antibiotics.
- Uncontrolled diabetes mellitus as defined by the investigator.
- Chronic symptomatic congestive heart failure (Class III or IV of the New York Heart. Association Classification for Heart Disease; AppendixG).
- Unstable angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months of signing the ICD.
- Clinically significant cardiac arrhythmia that is symptomatic or requires treatment, or asymptomatic sustained ventricular tachycardia. Subjects with controlled atrial fibrillation that is asymptomatic are eligible.
- Pregnant or lactating females.
Prior history of malignancies, unless the subject has been free of the disease for ≥ 3 years of signing the informed consent. Exceptions to the ≥ 3 year time limit include history of the following:
- Basal cell carcinoma of the skin.
- Squamous cell carcinoma of the skin.
- Carcinoma in situ of the cervix.
- Carcinoma in situ of the breast.
- Carcinoma in situ of the bladder.
- Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b). (The TNM staging system is based on the extent of the tumor (T), whether cancer cells have spread to nearby (regional) lymph nodes (N), and whether distant (to other parts of the body) metastasis (M) has occurred).
- Known seropositivity for or history of active viral infection with Human Immunodeficiency Virus (HIV).
Seropositive for or active viral infection with Hepatitis B virus (HBV):
- HBV surface antigen positive.
HBV surface antigen negative, HBV surface antibody positive and/or HBV core antibody positive and detectable viral deoxyribonucleic acid (DNA).
Note: Subjects who are HBV surface antigen negative and viral DNA negative are eligible.
- Subjects who had HBV but have received an antiviral treatment and show no detectable viral DNA within 6 months of signing the ICD are eligible.
- Subjects who exhibit the classical vaccination profile of HBV surface antibody positive, HBV core antibody negative, and HBV surface antigen negative are eligible.
- Known seropositivity for or active viral infection with Hepatitis C virus (HCV).
- Subjects who are at a high risk for a thromboembolic event and are not willing to take venous thromboembolic event (VTE) prophylaxis.
Any of the following laboratory abnormalities:
- Absolute neutrophil count (ANC) ≤ 1,000 cells/mm3 (1.0 x 109/L) unless secondary to bone marrow involvement by lymphoma as demonstrated by recent bone marrow aspiration and bone marrow biopsy.
- Platelet count ≤ 50,000/mm3 (50 x 109/L) unless secondary to bone marrow involvement by lymphoma as demonstrated by recent bone marrow aspiration and bone marrow biopsy. Note that growth factors or transfusions should not be administered during screening for the sole purpose of helping a subject exceed these exclusionary laboratory values.
- Serum Aspartate Transaminase/Serum Glutamic Oxaloacetic Transaminase (AST/SGOT) or Alanine Transaminase/Serum Glutamic Pyruvate Transaminase (ALT/SGPT) > 3.0 x Upper Limit of Normal (ULN) or > 5.0 x ULN in cases of documented liver involvement by lymphoma.
- Serum bilirubin > 1.5 x ULN or > 3.0 x ULN in cases of Gilbert's Syndrome and documented liver involvement by lymphoma.
Calculated creatinine clearance using the Cockcroft-Gault formula (Cockcroft, 1976).
- For subjects enrolling in Part 1 creatinine clearance value must be < 30 mL/min
- For subjects enrolling in Part 2 creatinine clearance value must be < 60 mL/min
- Corrected QT interval (QTc) prolongation (defined as a QTc > 450 msec for males and > 470 msec for females [Fridericia's correction] echocardiograms (ECGs) or other clinically significant ECG abnormalities as assessed by the investigator. An average of 3 QTc intervals may be obtained if necessary.
- Evidence of Tumor Lysis Syndrome (TLS) per the Cairo-Bishop definition of laboratory TLS ([Appendix F] subjects may be enrolled upon correction of electrolyte abnormalities).
- Prior exposure to Bruton Tyrosine Kinase inhibitors.
- Chemotherapy, radiotherapy, investigational anti cancer therapy or major surgery within 28 days of Day 1 dosing.
- Use of systemic corticosteroids in doses greater than prednisone equivalent 20 mg/day within 3 weeks prior to the first dose of study drug treatment.
- Concomitant use of medicines known to cause QT prolongation or torsades de pointes (Appendix I).
- Chronic use of H2 antagonists or proton pump inhibitors or their use within 7 days of first dose of study drug treatment. Subjects with chronic gastroesophageal reflux disease, dyspepsia, and peptic ulcer disease, should be carefully evaluated for their suitability for this treatment prior to enrollment in this study.
- Gastrointestinal abnormalities including the ability to take oral medication, require intravenous (IV) alimentation, or prior surgical procedures affecting absorption.
- History of hypersensitivity reaction to Rituximab.
- Any vaccinations incorporating the use of a live vaccine within 3 weeks from first dose.
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: NVT
- Interventioneel model: Opdracht voor een enkele groep
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Experimenteel: CC-292 with Rituximab
Dose Escalation
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Cohort 1: 375 mg CC-292 will be administered twice a day on Days 1-28 Cohort 2: 500 mg CC-292 will be administered twice a day on Days 1-28
Cohort 1: Rituximab once per cycle Cohort 2: Rituximab once per cycle
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Adverse Events
Tijdsspanne: Up to a year
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Number of participants with adverse events
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Up to a year
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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PK-Cmax
Tijdsspanne: Tot 15 dagen
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Maximale waargenomen plasmaconcentratie
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Tot 15 dagen
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PK-Tmax
Tijdsspanne: Up to 15 days
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Time to maximum observed plasma concentration of CC-292 in combination with Rituximab.
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Up to 15 days
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PK-λz
Tijdsspanne: Up to 15 days
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Terminal phase rate constant.
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Up to 15 days
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PK-t1/2
Tijdsspanne: Up to 15 days
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Estimate of the terminal phase half-life in plasma.
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Up to 15 days
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PK-AUC (0-t)
Tijdsspanne: Up to 15 days
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Area under the plasma concentration-time curve from time zero to the last quantifiable time point.
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Up to 15 days
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PK-AUC0-∞
Tijdsspanne: Tot 15 dagen
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Oppervlakte onder de tijdcurve van de plasmaconcentratie vanaf tijd nul geëxtrapoleerd naar oneindig.
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Tot 15 dagen
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Efficacy
Tijdsspanne: Up to 2 years
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To evaluate the preliminary efficacy of CC-292 in combination with Rituximab, including Response Rate, Duration of Response and Progression-Free Survival
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Up to 2 years
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Medewerkers en onderzoekers
Sponsor
Onderzoekers
- Studie directeur: Kenichi Takeshita, MD, Celgene
Studie record data
Bestudeer belangrijke data
Studie start
Primaire voltooiing (Werkelijk)
Studie voltooiing (Werkelijk)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Schatting)
Updates van studierecords
Laatste update geplaatst (Schatting)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
- Ziekten van het immuunsysteem
- Neoplasmata per histologisch type
- Neoplasmata
- Lymfoproliferatieve aandoeningen
- Lymfatische ziekten
- Immunoproliferatieve aandoeningen
- Leukemie, B-cel
- Lymfoom
- Leukemie
- Leukemie, lymfatische, chronische, B-cel
- Leukemie, Lymfoïde
- Fysiologische effecten van medicijnen
- Antireumatische middelen
- Antineoplastische middelen
- Immunologische factoren
- Antineoplastische middelen, immunologisch
- Rituximab
Andere studie-ID-nummers
- CC-292-CLL-002
- 2012-003767-21 (EudraCT-nummer)
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .
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