Pomalidomide in Relapsed and Refractory Multiple Myeloma (RRMM)

Multiple Myeloma Clinical Trial

— MUKseven  

Official title:

Pomalidomide in Relapsed and Refractory Multiple Myeloma (RRMM)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02406222
• Other study ID #: HM13/10758
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 2016
• Est. completion date: June 2023

Study information

• Verified date: May 2022
• Source: University of Leeds
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is determining whether the addition of cyclophosphamide to pomalidomide and dexamethasone improves progression free survival in patients with relapsed refractory myeloma (RRMM) compare to pomalidomide and dexamethasone alone. Patients will be randomised on a 1:1 basis to receive CPD or Pd. Treatment will be continued until disease progression or unacceptable toxicity.

Description:

Multiple myeloma is the second most common hematologic malignancy in the European Union (EU), responsible for an estimated 21,000 deaths in the EU in 2008. For patients that relapse or are refractory to current standard treatment (combination of bortezomib/lenalidomide, dexamethasone and an alkylating agent) there are few options available and therefore the prognosis within this group is often poor with response to treatment decreasing with successive relapses until resistant disease develops. . Current standard treatment at first relapse in the UK is the use of bortezomib in combination with dexamethasone and cyclophosphamide. Another common treatment is lenalidomide given with dexamethasone and cyclophosphamide. The addition of cyclophosphamide has demonstrated to improve treatment outcomes whilst being tolerated well. A recent clinical study has shown the addition of cyclophosphamide to the combination of pomalidomide and dexamethasone has shown to be safe and tolerable and beneficial in terms of treatment outcomes. The primary aim of this study is to investigate whether the addition of cyclophosphamide to pomalidomide and dexamethasone leads to an improved progression free survival. A secondary aim is to identify markers from clinical material that will predict response to pomalidomide in a group of relapsed and refractory multiple myeloma (RRMM) patients to provide important information for use in discussions with NICE on how best to improve the value and use of pomalidomide in the UK in the RRMM setting.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 124
• Est. completion date: June 2023
• Est. primary completion date: December 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosed with symptomatic multiple myeloma (according to International Myeloma Working Group (IMWG) 2009 criteria) and have measurable disease

• Participants must require therapy for relapsed and/or refractory disease

• Participants must have received = 2 treatment lines of anti-myeloma therapy (induction therapy followed by autologous stem-cell transplantation (ASCT) and consolidation/maintenance will be considered as one line).

• Participants must have received prior treatment with both lenalidomide and proteasome inhibitor, either as single agents or in combination regimens

• All participants must have failed treatment with either lenalidomide and proteasome inhibitor in one of the following ways:

1. Documented progressive disease on or within 60 days of completing treatment with lenalidomide and/or proteasome inhibitor ; or

2. In case of prior response [= partial response (PR)] to lenalidomide or proteasome inhibitor, participants must have relapsed within 6 months after stopping treatment with lenalidomide and/or proteasome inhibitor containing regimens; or

3. Participants who have not had a = minimal response (MR) despite receiving at least 4 cycles of treatment or who have developed intolerance/toxicity after a minimum of two cycles of lenalidomide and/or proteasome inhibitor containing regimen

• Patients must have received adequate prior alkylator therapy in one of the following ways

1. As part of a stem cell transplant; or

2. A minimum of 4 consecutive cycles of an alkylator based therapy; or

3. Progression on treatment with an alkylator; provided that the participant received at least 2 cycles of an alkylator containing therapy.

• Life expectancy of at least 3 months

• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2

• Required laboratory values within 14 days of treatment:

• Absolute neutrophil count = 1.0 x109 /L (growth factor support is permitted)

• Platelet count = 30 x 109/L (platelet transfusion is permitted)

• Creatinine clearance > 30 mL/min

• Corrected serum calcium = 3.5 mmol/L

• Haemoglobin = 8 g/dL (blood transfusion support is permitted)

• Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) < 3 times Upper Limit of Normal (ULN)

• Serum total bilirubin < 17 µmol/l

• Participants must consent to provide the bone marrow samples specified at screening and throughout the trial, in order to enter the trial. Confirmation of receipt of the sample from the lab must be received before treatment commences..

• Able to give informed consent and willing to follow trial protocol

• Aged over 18 or over

• Females of childbearing potential (FCBP) must agree to utilise one reliable form of contraception for 28 days prior to starting trial treatment, during the trial, and for 28 days after trial treatment discontinuation and even in the case of dose interruption and must agree to regular pregnancy testing during this timeframe

• Females must agree to abstain from breastfeeding during trial participation and 28 days after trial drug discontinuation

• Males must agree to use a latex condom during any sexual contact with FCBP during the trial, including during any dose interruptions and for 28 days following discontinuation from this trial even if he has undergone a successful vasectomy

• Males must also agree to refrain from donating semen or sperm while on pomalidomide, including during any dose interruptions and for 28 days after discontinuation from this trial

• All participants must agree to refrain from donation blood while on trial drug, including during dose interruptions and for 28 days after discontinuation from this trial

Exclusion Criteria:

• Previous therapy with pomalidomide

• Hypersensitivity to thalidomide, lenalidomide, cyclophosphamide or dexamethasone

• Participants with non-secretory multiple myeloma

• Peripheral neuropathy = Grade 3

• Participants who have received an allogeneic bone marrow or allogeneic peripheral blood stem cell transplant

• Participants who are planned for a stem cell transplant post MUK Seven trial treatment

• Antitumour therapies including investigational medicinal products at any dose within 28 days before the start of protocol treatment (or 5 half-lives, whichever is longer). Bisphosphonates for bone disease and radiotherapy for palliative intent are permitted.

• Participants with any of the following

1. Uncontrolled congestive heart failure

2. Myocardial infarction within 12 months prior to starting trial treatment

3. Unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris.

• Participants with gastrointestinal disease that may significantly alter absorption of pomalidomide

• Participants with a history of other malignancies within 5 years before the date of study entry (exceptions are squamous and basal cell carcinomas of the skin, carcinoma in situ of the cervix or breast, or other non-invasive lesion that is considered cured with minimal risk of recurrence within 5 years).

• Participants unable or unwilling to undergo antithrombotic prophylactic treatment

• Pregnant or breastfeeding females

• Participants known to be seropositive for HIV, or active infectious hepatitis A, B or C

• Any condition including the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she were to participate in the trial

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Pomalidomide
Chemotherapy
• Dexamethasone
Chemotherapy
• Cyclophosphamide
Chemotherapy

Locations

Country	Name	City	State
United Kingdom	Belfast Health & Social Care Trust	Belfast
United Kingdom	Birmingham Heartlands Hospital	Birmingham
United Kingdom	University of Birmingham NHS Foundation Trust	Birmingham
United Kingdom	Royal Sussex County Hospital	Brighton
United Kingdom	Queens Hospital	Burton on Trent
United Kingdom	University Hospital of Wales NHS Trust	Cardiff
United Kingdom	Ninewells Hospital	Dundee
United Kingdom	Beatson Oncology Centre	Glasgow
United Kingdom	St James's Hopsital	Leeds
United Kingdom	University Hospital of Leicester NHS Trust	Leicester
United Kingdom	Guy's and St Thomas' NHS Foundation Trust	London
United Kingdom	Imperial College Hospital	London
United Kingdom	St Bartholomew Hospital	London
United Kingdom	The Royal Marsden NHS Foundation Trust	London
United Kingdom	University College London Hospital	London
United Kingdom	Central Manchester Univeristy Hospital NHS Trust	Manchester
United Kingdom	The Christie Hospital	Manchester
United Kingdom	Churchill Hospital	Oxford
United Kingdom	Sheffield Teaching Hospitals NHS FoundationTrust	Sheffield
United Kingdom	University Hospital of North Tees	Stockton-on-Tees
United Kingdom	New Cross Hospital	Wolverhampton

Sponsors (3)

Lead Sponsor	Collaborator
University of Leeds	Celgene, Myeloma UK

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival	To determine whether the addition of cyclophosphamide to pomalidomide and dexamethasone (CPD) improves progression-free survival in patients with relapsed refractory myeloma (RRMM) in the UK, compared to pomalidomide and dexamethasone (Pd) alone	From randomisation up to 72 months
Secondary	Maximum response overall	To determine the maximum response achieved from treatment	From the start of treatment up to 72 months
Secondary	Response to treatment	Determine the response to treatment	From the start of treatment up to 72 months
Secondary	Clinical benefit rate overall	Determine any clinical benefit that is derived from treatment	From the start of treatment up to 72 months
Secondary	Time to maximum response	Determine the time to maximum response to treatment	From the start of treatment up to 72 months
Secondary	Duration of response	Determine the duration that the response to treatment lasts for	From the start of treatment up to 72 months
Secondary	Overall survival	Determine overall survival for all patients that receive treatment	Date of randomisation to death, up to 72 months
Secondary	Treatment compliance	Measured by treatment delays and missed treatment doses	From the start of treatment up to end of treatment
Secondary	Safety and Toxicity	Measured by adverse reactions and serious adverse event reporting	Time of registration to 28 days post treatment discontinuation