Clinical trial NCT02045017: Efficacy and Safety of Pomalidomide and Dexamethasone in RRMM Patients With Renal Insufficiency
Official title: A Phase 2 Multicenter, Open-label Study to Determine the Efficacy and Safety of Pomalidomide (CC-4047) in Combination With Low-Dose Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma and Moderate or Severe Renal Impairment Including Subjects Undergoing Hemodialysis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
Relapsed Multiple Myeloma
Refactory Multiple Myeloma
Renal Insufficiency
Pomalidomide
Dexamethasone
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2014-01-24
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: Inclusion Criteria:

- Subjects must satisfy the following criteria to be enrolled in the study.

1. 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).

5. 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.

6. 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.

1. Impaired renal function must be due to multiple myeloma which needs to be confirmed by kidney biopsy.
2. 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

1. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
2. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
3. Renal insufficiency due to other reasons than multiple myeloma or due to hypocalcaemia only.
4. Prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥ 5 years; exceptions include the following:

   1. Basal or squamous cell carcinoma of the skin
   2. Carcinoma in situ of the cervix or breast
   3. Incidental histological finding of prostate cancer (Tumour lymphNode Metastasis stage of T1a or T1b)

6. Previous therapy with pomalidomide. 7. Hypersensitivity to thalidomide, lenalidomide, or dexamethasone (this includes ≥ Grade 3 rash during prior thalidomide or lenalidomide therapy).

10. Subjects who are planning for or who are eligible for stem cell transplant.

Primary outcomes:
measure: Evaluate efficacy of the combination of pomalidomide and low-dose dexamethasone in subjects with RRMM and impaired renal function
timeFrame: Approximately 2 years
Secondary outcomes:
measure: Assessment of renal response according to the criteria defined by Dimopoulos and Ludwig (Dimopoulos, 2009; Dimopoulos, 2010 b,c; Ludwig, 2010).
timeFrame: Approximately 2 years
measure: Time to Myeloma response
timeFrame: Approximately 2 years
measure: Time to renal response
timeFrame: Approximately 2 years
measure: Duration of response
timeFrame: Approximately 2 years
measure: Progression-free survival
timeFrame: Approximately 2 years
measure: Time to progression
timeFrame: Approximately 2 years
measure: Overall Survival
timeFrame: Approximately 2 years
measure: Adverse events (AEs) assessment (type, frequency, seriousness, severity, relationship to pomalidomide and/or dexamethasone and outcomes) including second primary malignancy (SPM).
timeFrame: Approximately 2 years
Other outcomes:
Locations:
city: Linz
country: Austria
facility: Krankenhaus der Elisabethinen Linz, I Interne Abteilung
city: Wien
country: Austria
facility: Medizinische Universitat Wien
city: Wien
country: Austria
facility: Wilhelminenspital der Stadt Wien
city: Limoges cedex
country: France
facility: Hopital Dypuytren-CHU de Limoges
city: Paris
country: France
facility: Hopital Saint Louis
city: Poitiers
country: France
facility: CHU de Poitiers
city: Neuenheimer Feld 410
country: Germany
facility: Medizinische Klinik und Poliklinik V Hamatologie, Onkologie und Rheumatologie
city: Tubingen
country: Germany
facility: University Hospital Tubingen
city: Athens
country: Greece
facility: Alexandra Hospital, University of Athens
city: Ancona
country: Italy
facility: Azienda Ospedaliero Universitaria Ospedali
city: Lecco
country: Italy
facility: S.C. Oncologia Medica
city: Milano
country: Italy
facility: Ospedale Maggiore Policlinico Mangiagalli Regina Elena
city: Reggio Emilia
country: Italy
facility: Arcispedale Santa Maria Nuova
city: Amsterdam
country: Netherlands
facility: VU University Medical Center VU Medisch Centrum
city: Rotterdam
country: Netherlands
facility: Daniel den Hoed Kliniek Medical Oncology, Erasmus MC
city: Madrid
country: Spain
facility: Hospital de La Princesa
city: Salamanca
country: Spain
facility: CEIC Hospital Universitario de Salamanca
city: Valencia
country: Spain
facility: Hospital Universitario Doctor Peset
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital UHB NHS Foundation Trust
city: Dundee
country: United Kingdom
facility: Ninewells Hospital and Medical School
city: Headington
country: United Kingdom
facility: Oxford Radcliffe Hospital ICRF Medical Oncology Unit
city: London
country: United Kingdom
facility: St Thomas' HospitalGuy's Hospital Dept. of Haematology
Study officials:
affiliation: Celgene
name: Elisabeth Kueenburg, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.