Efficacy and Safety of Pomalidomide and Dexamethasone in RRMM Patients With Renal Insufficiency

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02045017
• Other study ID #: CC-4047-MM-013
• Secondary ID: 2013-001903-36
• Status: Completed
• Phase: Phase 2
• Start date: February 28, 2014
• Est. completion date: July 28, 2021

Study information

• Verified date: August 2021
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 81
• Est. completion date: July 28, 2021
• Est. primary completion date: January 27, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Renal Insufficiency

Intervention

Drug:
• Pomalidomide and Dexamethasone

Locations

Country	Name	City	State
Austria	Krankenhaus der Elisabethinen Linz, I Interne Abteilung	Linz
Austria	Medizinische Universitat Wien	Wien
Austria	Wilhelminenspital der Stadt Wien	Wien
France	Hopital Dypuytren-CHU de Limoges	Limoges cedex
France	Hopital Saint Louis	Paris
France	CHU de Poitiers	Poitiers
Germany	Medizinische Klinik und Poliklinik V Hamatologie, Onkologie und Rheumatologie	Neuenheimer Feld 410
Germany	University Hospital Tubingen	Tubingen
Greece	Alexandra Hospital, University of Athens	Athens
Italy	Azienda Ospedaliero Universitaria Ospedali	Ancona
Italy	S.C. Oncologia Medica	Lecco
Italy	Ospedale Maggiore Policlinico Mangiagalli Regina Elena	Milano
Italy	Arcispedale Santa Maria Nuova	Reggio Emilia
Netherlands	VU University Medical Center VU Medisch Centrum	Amsterdam
Netherlands	Daniel den Hoed Kliniek Medical Oncology, Erasmus MC	Rotterdam
Spain	Hospital de La Princesa	Madrid
Spain	CEIC Hospital Universitario de Salamanca	Salamanca
Spain	Hospital Universitario Doctor Peset	Valencia
United Kingdom	Queen Elizabeth Hospital UHB NHS Foundation Trust	Birmingham
United Kingdom	Ninewells Hospital and Medical School	Dundee
United Kingdom	Oxford Radcliffe Hospital ICRF Medical Oncology Unit	Headington
United Kingdom	St Thomas' HospitalGuy's Hospital Dept. of Haematology	London

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

Austria,  France,  Germany,  Greece,  Italy,  Netherlands,  Spain,  United Kingdom, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate efficacy of the combination of pomalidomide and low-dose dexamethasone in subjects with RRMM and impaired renal function	Overall response rate determined by Myeloma responses determined by modified IMWG criteria	Approximately 2 years
Secondary	Assessment of renal response according to the criteria defined by Dimopoulos and Ludwig (Dimopoulos, 2009; Dimopoulos, 2010 b,c; Ludwig, 2010).	Assessment of renal response according to the criteria defined by Ludwig and Dimopoulos	Approximately 2 years
Secondary	Time to Myeloma response	Evaluated according to the CTCAE grading	Approximately 2 years
Secondary	Time to renal response	Evaluated according to the CTCAE grading	Approximately 2 years
Secondary	Duration of response	Evaluated according to the CTCAE grading	Approximately 2 years
Secondary	Progression-free survival	Evaluated according to the CTCAE grading	Approximately 2 years
Secondary	Time to progression	Evaluated according to the CTCAE grading	Approximately 2 years
Secondary	Overall Survival	Evaluated according to the CTCAE grading	Approximately 2 years
Secondary	Adverse events (AEs) assessment (type, frequency, seriousness, severity, relationship to pomalidomide and/or dexamethasone and outcomes) including second primary malignancy (SPM).	Pharmacokinetics (PK) of pomalidomide in subjects with RRMM and impaired renal function (moderate to severe renal impairment).	Approximately 2 years