Pomalidomide in Relapsed and Refractory Multiple Myeloma (RRMM)

NCT02406222 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: HM13/10758
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 21

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.

Conditions

Multiple Myeloma

Keywords

Relapsed; Refractory; Pomalidomide; Dexamethasone; Cyclophosphamide

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Maximum response overall

  From the start of treatment up to 72 months

• Response to treatment

  From the start of treatment up to 72 months

• Clinical benefit rate overall

  From the start of treatment up to 72 months

• Time to maximum response

  From the start of treatment up to 72 months

• Duration of response

  From the start of treatment up to 72 months

Study Arms (2)

Pomalidomide and Dexamethasone

ACTIVE COMPARATOR

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; Drug: Dexamethasone

Pomalidomide Dexamethasone Cyclophosphamide

EXPERIMENTAL

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; Drug: Dexamethasone; Drug: Cyclophosphamide

Interventions

Pomalidomide DRUG

Chemotherapy

Pomalidomide Dexamethasone Cyclophosphamide; Pomalidomide and Dexamethasone

Dexamethasone DRUG

Chemotherapy

Pomalidomide Dexamethasone Cyclophosphamide; Pomalidomide and Dexamethasone

Cyclophosphamide DRUG

Chemotherapy

Pomalidomide Dexamethasone Cyclophosphamide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Leeds: lead
• Myeloma UK: collaborator
• Celgene: collaborator

Study Sites (21)

Belfast Health & Social Care Trust

Belfast, BT9 7AB, United Kingdom

Location

University of Birmingham NHS Foundation Trust

Birmingham, B15 2TH, United Kingdom

Location

Birmingham Heartlands Hospital

Birmingham, B9 5SS, United Kingdom

Location

Royal Sussex County Hospital

Brighton, BN2 5BE, United Kingdom

Location

Queens Hospital

Burton-on-Trent, DE13 0RB, United Kingdom

Location

University Hospital of Wales NHS Trust

Cardiff, CF14 4XW, United Kingdom

Location

Ninewells Hospital

Dundee, DD1 9SY, United Kingdom

Location

Beatson Oncology Centre

Glasgow, United Kingdom

Location

St James's Hopsital

Leeds, LS9 7TF, United Kingdom

Location

University Hospital of Leicester NHS Trust

Leicester, LE1 5WW, United Kingdom

Location

St Bartholomew Hospital

London, EC1M 6BQ, United Kingdom

Location

University College London Hospital

London, NW1 2BU, United Kingdom

Location

Guy's and St Thomas' NHS Foundation Trust

London, SE1 9RT, United Kingdom

Location

The Royal Marsden NHS Foundation Trust

London, SW3 6JJ, United Kingdom

Location

Imperial College Hospital

London, W2 1NY, United Kingdom

Location

Central Manchester Univeristy Hospital NHS Trust

Manchester, M13 9WL, United Kingdom

Location

The Christie Hospital

Manchester, M20 4BX, United Kingdom

Location

Churchill Hospital

Oxford, OX3 7LE, United Kingdom

Location

Sheffield Teaching Hospitals NHS FoundationTrust

Sheffield, S10 2RB, United Kingdom

Location

University Hospital of North Tees

Stockton-on-Tees, TS19 8PE, United Kingdom

Location

New Cross Hospital

Wolverhampton, WV10 0QP, United Kingdom

Location

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Interventions

pomalidomide; Dexamethasone; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Martin Kaiser, Dr

  Royal Marsden NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2015
• First Posted: April 2, 2015
• Study Start: March 1, 2016
• Primary Completion: December 1, 2022
• Study Completion: June 1, 2025
• Last Updated: December 5, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (21)