MUKseven: Pomalidomide in Relapsed and Refractory Multiple Myeloma (RRMM)

Sponsor

University of Leeds (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02406222

Collaborator

Myeloma UK (Other), Celgene (Industry)

124

Enrollment

Locations

Arms

Duration (Months)

5.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Pomalidomide Drug: Dexamethasone Drug: Cyclophosphamide	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

124 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Pomalidomide in Relapsed and Refractory Multiple Myeloma (RRMM)

Study Start Date :

Mar 1, 2016

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Pomalidomide and Dexamethasone Pomalidomide and Dexamethasone will be administered as part of a 28 day cycle. Patients will continue with their treatment until disease progression, intolerance, toxicity or withdrawal. Dosing schedule: Pomalidomide 4mg orally on days 1-21 Dexamethasone 40mg orally on days 1, 8, 15 and 22	Drug: Pomalidomide Chemotherapy Drug: Dexamethasone Chemotherapy
Experimental: Pomalidomide Dexamethasone Cyclophosphamide Pomalidomide, Dexamethasone and Cyclophosphamide will be administered as part of a 28 day cycle. Patients will continue with their treatment until disease progression, intolerance, toxicity or withdrawal. Dosing schedule: Pomalidomide 4mg orally on days 1-21 Dexamethasone 40mg orally on days 1, 8, 15 and 22 Cyclophosphamide 500mg orally on days 1, 8 and 15	Drug: Pomalidomide Chemotherapy Drug: Dexamethasone Chemotherapy Drug: Cyclophosphamide Chemotherapy

Arm

Intervention/Treatment

Active Comparator: Pomalidomide and Dexamethasone

Pomalidomide and Dexamethasone will be administered as part of a 28 day cycle. Patients will continue with their treatment until disease progression, intolerance, toxicity or withdrawal. Dosing schedule: Pomalidomide 4mg orally on days 1-21 Dexamethasone 40mg orally on days 1, 8, 15 and 22

Drug: Pomalidomide

Chemotherapy

Drug: Dexamethasone

Chemotherapy

Experimental: Pomalidomide Dexamethasone Cyclophosphamide

Pomalidomide, Dexamethasone and Cyclophosphamide will be administered as part of a 28 day cycle. Patients will continue with their treatment until disease progression, intolerance, toxicity or withdrawal. Dosing schedule: Pomalidomide 4mg orally on days 1-21 Dexamethasone 40mg orally on days 1, 8, 15 and 22 Cyclophosphamide 500mg orally on days 1, 8 and 15

Drug: Pomalidomide

Chemotherapy

Drug: Dexamethasone

Chemotherapy

Drug: Cyclophosphamide

Chemotherapy

Outcome Measures

Primary Outcome Measures

Progression free survival [From randomisation up to 72 months]
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

Secondary Outcome Measures

Maximum response overall [From the start of treatment up to 72 months]
To determine the maximum response achieved from treatment
Response to treatment [From the start of treatment up to 72 months]
Determine the response to treatment
Clinical benefit rate overall [From the start of treatment up to 72 months]
Determine any clinical benefit that is derived from treatment
Time to maximum response [From the start of treatment up to 72 months]
Determine the time to maximum response to treatment
Duration of response [From the start of treatment up to 72 months]
Determine the duration that the response to treatment lasts for
Overall survival [Date of randomisation to death, up to 72 months]
Determine overall survival for all patients that receive treatment
Treatment compliance [From the start of treatment up to end of treatment]
Measured by treatment delays and missed treatment doses
Safety and Toxicity [Time of registration to 28 days post treatment discontinuation]
Measured by adverse reactions and serious adverse event reporting

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

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

As part of a stem cell transplant; or
A minimum of 4 consecutive cycles of an alkylator based therapy; or
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

Uncontrolled congestive heart failure
Myocardial infarction within 12 months prior to starting trial treatment
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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Belfast Health & Social Care Trust	Belfast	United Kingdom	BT9 7AB
2	University of Birmingham NHS Foundation Trust	Birmingham	United Kingdom	B15 2TH
3	Birmingham Heartlands Hospital	Birmingham	United Kingdom	B9 5SS
4	Royal Sussex County Hospital	Brighton	United Kingdom	BN2 5BE
5	Queens Hospital	Burton on Trent	United Kingdom	DE13 0RB
6	University Hospital of Wales NHS Trust	Cardiff	United Kingdom	CF14 4XW
7	Ninewells Hospital	Dundee	United Kingdom	DD1 9SY
8	Beatson Oncology Centre	Glasgow	United Kingdom
9	St James's Hopsital	Leeds	United Kingdom	LS9 7TF
10	University Hospital of Leicester NHS Trust	Leicester	United Kingdom	LE1 5WW
11	St Bartholomew Hospital	London	United Kingdom	EC1M 6BQ
12	University College London Hospital	London	United Kingdom	NW1 2BU
13	Guy's and St Thomas' NHS Foundation Trust	London	United Kingdom	SE1 9RT
14	The Royal Marsden NHS Foundation Trust	London	United Kingdom	SW3 6JJ
15	Imperial College Hospital	London	United Kingdom	W2 1NY
16	Central Manchester Univeristy Hospital NHS Trust	Manchester	United Kingdom	M13 9WL
17	The Christie Hospital	Manchester	United Kingdom	M20 4BX
18	Churchill Hospital	Oxford	United Kingdom	OX3 7LE
19	Sheffield Teaching Hospitals NHS FoundationTrust	Sheffield	United Kingdom	S10 2RB
20	University Hospital of North Tees	Stockton-on-Tees	United Kingdom	TS19 8PE
21	New Cross Hospital	Wolverhampton	United Kingdom	WV10 0QP