Efficacy and Safety of Pomalidomide and Dexamethasone in RRMM Patients With Renal Insufficiency
Study Details
Study Description
Brief Summary
The primary purpose of the study is to determine the safety and efficacy and to generate PK and biomarker data for the combination of Pomalidomide and low-dose Dexamethasone in patients with relapsed or refractory multiple myeloma, with moderate or severe renal impairment.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 2 |
Detailed Description
The study will consist of a Screening phase within 28 days prior to cycle 1 day 1. Subjects once enrolled will enter the Treatment phase, in which patients will be treated until progression, or study discontinuation due to other reasons. Subjects will enter the long term Follow-up phase of the study where data will be collected every 3 months for up to 5 years on Secondary primary malignancies, survival, subsequent anti myeloma treatments and date of progression. Subjects will be recruited into one of 3 cohorts depending on the severity of their renal impairment.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Pomalidomide and low dose Dexamethasone Pomalidomide 4mg, and low dose Dexamethasone, starting at 40mgs(≤ 75 years old) or 20 mg/day (> 75 years old) |
Drug: Pomalidomide and Dexamethasone
Other Names:
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Outcome Measures
Primary Outcome Measures
- Evaluate efficacy of the combination of pomalidomide and low-dose dexamethasone in subjects with RRMM and impaired renal function [Approximately 2 years]
Overall response rate determined by Myeloma responses determined by modified IMWG criteria
Secondary Outcome Measures
- Assessment of renal response according to the criteria defined by Dimopoulos and Ludwig (Dimopoulos, 2009; Dimopoulos, 2010 b,c; Ludwig, 2010). [Approximately 2 years]
Assessment of renal response according to the criteria defined by Ludwig and Dimopoulos
- Time to Myeloma response [Approximately 2 years]
Evaluated according to the CTCAE grading
- Time to renal response [Approximately 2 years]
Evaluated according to the CTCAE grading
- Duration of response [Approximately 2 years]
Evaluated according to the CTCAE grading
- Progression-free survival [Approximately 2 years]
Evaluated according to the CTCAE grading
- Time to progression [Approximately 2 years]
Evaluated according to the CTCAE grading
- Overall Survival [Approximately 2 years]
Evaluated according to the CTCAE grading
- Adverse events (AEs) assessment (type, frequency, seriousness, severity, relationship to pomalidomide and/or dexamethasone and outcomes) including second primary malignancy (SPM). [Approximately 2 years]
Pharmacokinetics (PK) of pomalidomide in subjects with RRMM and impaired renal function (moderate to severe renal impairment).
Eligibility Criteria
Criteria
Inclusion Criteria:
- Subjects must satisfy the following criteria to be enrolled in the study.
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Subjects must have documented diagnosis of multiple myeloma and have measurable disease (serum M-protein ≥ 0.5 g/dL or urine M-protein ≥ 200 mg/24 hours).
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Subjects must have had at least 1 prior antimyeloma regimen including lenalidomide and documented progression as per the International Myeloma Working Group uniform response criteria (Durie, 2006) during or after the last antimyeloma regimen. Induction therapy followed by Autologous Stem Cell Transplant and consolidation/ maintenance will be considered as one regimen.
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Subjects must have an impaired renal function with an estimated Glomerular Filtrate Rate of < 45 mL/min/1.73 m2 according to the modification of diet in renal disease equation.
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Impaired renal function must be due to multiple myeloma which needs to be confirmed by kidney biopsy.
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Subjects may have acute myeloma related renal failure or chronic myeloma related renal failure; they may also have been treated with dialysis before, including dialysis with high cut off membranes.
Exclusion Criteria:
The presence of any of the following will exclude a subject from enrollment
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Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
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Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
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Renal insufficiency due to other reasons than multiple myeloma or due to hypocalcaemia only.
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Prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥ 5 years; exceptions include the following:
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Basal or squamous cell carcinoma of the skin
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Carcinoma in situ of the cervix or breast
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Incidental histological finding of prostate cancer (Tumour lymphNode Metastasis stage of T1a or T1b)
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Previous therapy with pomalidomide. 7. Hypersensitivity to thalidomide, lenalidomide, or dexamethasone (this includes ≥ Grade 3 rash during prior thalidomide or lenalidomide therapy).
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Subjects who are planning for or who are eligible for stem cell transplant.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Krankenhaus der Elisabethinen Linz, I Interne Abteilung | Linz | Austria | 4020 | |
2 | Medizinische Universitat Wien | Wien | Austria | 1090 | |
3 | Wilhelminenspital der Stadt Wien | Wien | Austria | 1160 | |
4 | Hopital Dypuytren-CHU de Limoges | Limoges cedex | France | 87042 | |
5 | Hopital Saint Louis | Paris | France | 75475 | |
6 | CHU de Poitiers | Poitiers | France | 86021 | |
7 | Medizinische Klinik und Poliklinik V Hamatologie, Onkologie und Rheumatologie | Neuenheimer Feld 410 | Germany | 69120 | |
8 | University Hospital Tubingen | Tubingen | Germany | 72076 | |
9 | Alexandra Hospital, University of Athens | Athens | Greece | 11528 | |
10 | Azienda Ospedaliero Universitaria Ospedali | Ancona | Italy | 60126 | |
11 | S.C. Oncologia Medica | Lecco | Italy | 23900 | |
12 | Ospedale Maggiore Policlinico Mangiagalli Regina Elena | Milano | Italy | 20122 | |
13 | Arcispedale Santa Maria Nuova | Reggio Emilia | Italy | 42100 | |
14 | VU University Medical Center VU Medisch Centrum | Amsterdam | Netherlands | 1081 HV | |
15 | Daniel den Hoed Kliniek Medical Oncology, Erasmus MC | Rotterdam | Netherlands | 3075 EA | |
16 | Hospital de La Princesa | Madrid | Spain | 28006 | |
17 | CEIC Hospital Universitario de Salamanca | Salamanca | Spain | 37007 | |
18 | Hospital Universitario Doctor Peset | Valencia | Spain | 46017 | |
19 | Queen Elizabeth Hospital UHB NHS Foundation Trust | Birmingham | United Kingdom | B15 2TH | |
20 | Ninewells Hospital and Medical School | Dundee | United Kingdom | DD1 9SY | |
21 | Oxford Radcliffe Hospital ICRF Medical Oncology Unit | Headington | United Kingdom | OX37LJ | |
22 | St Thomas' HospitalGuy's Hospital Dept. of Haematology | London | United Kingdom | SE1 9RT |
Sponsors and Collaborators
- Celgene
Investigators
- Study Director: Elisabeth Kueenburg, MD, Celgene
Study Documents (Full-Text)
None provided.More Information
Publications
- Dimopoulos M, Weisel K, van de Donk NWCJ, Ramasamy K, Gamberi B, Streetly M, Offidani M, Bridoux F, de la Rubia J, Mateos MV, Ardizzoia A, Kueenburg E, Collins S, Di Micco A, Rosettani B, Li Y, Bacon P, Sonneveld P. Pomalidomide Plus Low-Dose Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma and Renal Impairment: Results From a Phase II Trial. J Clin Oncol. 2018 Jul 10;36(20):2035-2043. doi: 10.1200/JCO.2017.76.1742. Epub 2018 Feb 2.
- Li Y, Wang X, O'Mara E, Dimopoulos MA, Sonneveld P, Weisel KC, Matous J, Siegel DS, Shah JJ, Kueenburg E, Sternas L, Cavanaugh C, Zaki M, Palmisano M, Zhou S. Population pharmacokinetics of pomalidomide in patients with relapsed or refractory multiple myeloma with various degrees of impaired renal function. Clin Pharmacol. 2017 Nov 8;9:133-145. doi: 10.2147/CPAA.S144606. eCollection 2017.
- CC-4047-MM-013
- 2013-001903-36