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

Phase 2

Completed

• Conditions: Multiple Myeloma
• Interventions: Drug: Pomalidomide and Dexamethasone

• Registration Number: NCT02045017
• Lead Sponsor: Celgene

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.

Study Timeline

• Study First Submitted: 2013-12-16
• Study First Submitted QC: 2014-01-23
• Study First Posted: 2014-01-24
• Study Start: 2014-02-28
• Primary Completion: 2017-01-27
• Study Completion: 2021-07-28
• Status Verified: 2021-08
• Last Update Submitted: 2021-08-25
• Last Update Posted: 2021-08-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 81

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).

2. 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.

3. 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.

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

5. 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)

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

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Pomalidomide and low dose Dexamethasone	Pomalidomide and Dexamethasone	Pomalidomide 4mg, and low dose Dexamethasone, starting at 40mgs(≤ 75 years old) or 20 mg/day (\> 75 years old)

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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 progression	Approximately 2 years	Evaluated according to the CTCAE grading
Overall Survival	Approximately 2 years	Evaluated according to the CTCAE grading
Progression-free survival	Approximately 2 years	Evaluated according to the CTCAE grading
Duration of response	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).
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

Trial Locations

Locations (22)

Arcispedale Santa Maria Nuova; 🇮🇹 Reggio Emilia, Italy

Oxford Radcliffe Hospital ICRF Medical Oncology Unit; 🇬🇧 Headington, United Kingdom

CHU de Poitiers; 🇫🇷 Poitiers, France

Queen Elizabeth Hospital UHB NHS Foundation Trust; 🇬🇧 Birmingham, United Kingdom

Wilhelminenspital der Stadt Wien; 🇦🇹 Wien, Austria

Ninewells Hospital and Medical School; 🇬🇧 Dundee, United Kingdom

CEIC Hospital Universitario de Salamanca; 🇪🇸 Salamanca, Spain

Medizinische Klinik und Poliklinik V Hamatologie, Onkologie und Rheumatologie; 🇩🇪 Neuenheimer Feld 410, Germany

Hospital de La Princesa; 🇪🇸 Madrid, Spain

Hospital Universitario Doctor Peset; 🇪🇸 Valencia, Spain

Hopital Dypuytren-CHU de Limoges; 🇫🇷 Limoges cedex, France

Medizinische Universitat Wien; 🇦🇹 Wien, Austria

Alexandra Hospital, University of Athens; 🇬🇷 Athens, Greece

University Hospital Tubingen; 🇩🇪 Tubingen, Germany

Azienda Ospedaliero Universitaria Ospedali; 🇮🇹 Ancona, Italy

Krankenhaus der Elisabethinen Linz, I Interne Abteilung; 🇦🇹 Linz, Austria

S.C. Oncologia Medica; 🇮🇹 Lecco, Italy

Ospedale Maggiore Policlinico Mangiagalli Regina Elena; 🇮🇹 Milano, Italy

Daniel den Hoed Kliniek Medical Oncology, Erasmus MC; 🇳🇱 Rotterdam, Netherlands

Hopital Saint Louis; 🇫🇷 Paris, France

VU University Medical Center VU Medisch Centrum; 🇳🇱 Amsterdam, Netherlands

St Thomas' HospitalGuy's Hospital Dept. of Haematology; 🇬🇧 London, United Kingdom