Clinical trial NCT02406222: Pomalidomide in Relapsed and Refractory Multiple Myeloma (RRMM)
Official title: Pomalidomide in Relapsed and Refractory Multiple Myeloma (RRMM)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Relapsed
Refractory
Pomalidomide
Dexamethasone
Cyclophosphamide
Lead sponsor: University of Leeds
Sponsor class: OTHER
Collaborators: name: Myeloma UK
name: Celgene
First posted: 2015-04-02
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression free survival
timeFrame: From randomisation up to 72 months
Secondary outcomes:
measure: Maximum response overall
timeFrame: From the start of treatment up to 72 months
measure: Response to treatment
timeFrame: From the start of treatment up to 72 months
measure: Clinical benefit rate overall
timeFrame: From the start of treatment up to 72 months
measure: Time to maximum response
timeFrame: From the start of treatment up to 72 months
measure: Duration of response
timeFrame: From the start of treatment up to 72 months
measure: Overall survival
timeFrame: Date of randomisation to death, up to 72 months
measure: Treatment compliance
timeFrame: From the start of treatment up to end of treatment
measure: Safety and Toxicity
timeFrame: Time of registration to 28 days post treatment discontinuation
Other outcomes:
Locations:
city: Belfast
country: United Kingdom
facility: Belfast Health & Social Care Trust
city: Birmingham
country: United Kingdom
facility: University of Birmingham NHS Foundation Trust
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
city: Brighton
country: United Kingdom
facility: Royal Sussex County Hospital
city: Burton on Trent
country: United Kingdom
facility: Queens Hospital
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales NHS Trust
city: Dundee
country: United Kingdom
facility: Ninewells Hospital
city: Glasgow
country: United Kingdom
facility: Beatson Oncology Centre
city: Leeds
country: United Kingdom
facility: St James's Hopsital
city: Leicester
country: United Kingdom
facility: University Hospital of Leicester NHS Trust
city: London
country: United Kingdom
facility: St Bartholomew Hospital
city: London
country: United Kingdom
facility: University College London Hospital
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
city: London
country: United Kingdom
facility: Imperial College Hospital
city: Manchester
country: United Kingdom
facility: Central Manchester Univeristy Hospital NHS Trust
city: Manchester
country: United Kingdom
facility: The Christie Hospital
city: Oxford
country: United Kingdom
facility: Churchill Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS FoundationTrust
city: Stockton-on-Tees
country: United Kingdom
facility: University Hospital of North Tees
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
Study officials:
affiliation: Royal Marsden NHS Foundation Trust
name: Martin Kaiser, Dr
role: PRINCIPAL_INVESTIGATOR
References: