Pembrolizumab Cyclophosphamide and Lenalidomide for Patients With Relapsed Multiple Myeloma

NCT03191981 | Withdrawn Phase 1 DMC

• 1 other identifier: HM16/87650
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 4

Brief Summary

This is a multi-centre phase I/II trial with an initial dose finding phase for cyclophosphamide and lenalidomide combined with fixed dose pembrolizumab for patients with relapsed or relapsed / refractory multiple myeloma (MM) that have had at least 1 prior line of therapy

Conditions

Myeloma Multiple

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicities (DLT) in dose finding phase

  Number of participants experiencing DLTs within the first cycle of treatment

  End of cycle 1 of treatment, 4 weeks

• Response rate

  Overall response rate to treatment

  From registration until disease progression, 2 years

Secondary Outcomes (6)

• Safety of trial treatment

  From registration until the end of the trial, 2 years

• Progression free survival (PFS)

  From registration to 6 & 12 months

• Maximum response

  From the start of treatment until the end of treatment, 2 years

• Duration of response

  From start of treatment until disease progression, 2 years

• Compliance to therapy

  From start of treatment until the end of treatment, 2 years

Other Outcomes (2)

• Overall survival

  12 months post registration

• Time to next treatment

  From end of treatment until starting the next treatment, 2 1/2 years

Study Arms (1)

Treatment

EXPERIMENTAL

Cyclophosphamide and lenalidomide combined with fixed dose pembrolizumab

Drug: Cyclophosphamide; Drug: Lenalidomide; Drug: Pembrolizumab

Interventions

Cyclophosphamide DRUG

Treatment for all patients will be with cyclophosphamide, lenalidomide and pembrolizumab at fixed doses.

Treatment

Lenalidomide DRUG

Treatment for all patients will be with cyclophosphamide, lenalidomide and pembrolizumab at fixed doses.

Also known as: Revlimid

Treatment

Pembrolizumab DRUG

Treatment for all patients will be with cyclophosphamide, lenalidomide and pembrolizumab at fixed doses.

Also known as: Keytruda

Treatment

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent for the trial and willing to follow the trial protocol.
• Be 18 years of age or greater on day of signing informed consent.
• Measurable disease with at least one of the following:
• Paraprotein greater than or equal to 5g/L
• Serum free light chains greater than or equal to 100mg/L with abnormal radio for light chain only
• myeloma
• Bence Jones protein greater than or equal to 200mg/24hr
• Have relapsed MM following 1 or more prior lines of therapy.
• Have achieved a partial response (PR or better based on investigator's determination of response by the International Myeloma Working Group (IMWG) criteria) to at least one prior regimen
• Have a performance status of 0-1 on the ECOG Performance Scale.
• Demonstrate adequate organ function as defined below, all screening laboratory tests are to be performed within 10 days prior to registration:
• Haematological
• Absolute neutrophil count greater than or equal to 1.0 x109 /L. Growth factor support is not permitted within 7 days prior to assessment
• Platelet count greater than or equal to 75 x 109/L. Platelet support is not permitted within 7 days prior to assessment.
• Haemoglobin greater than or equal to 90 g/L. Blood support is not permitted within 7 days prior to assessment.

You may not qualify if:

• Those with non-measurable disease, solitary bone or solitary extramedullary plasmacytoma, plasma cell leukaemia, POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
• Is currently participating and receiving trial therapy, or has participated in a trial of an investigational agent and received trial therapy or used an investigational device within 28 days prior to the first dose of trial treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to the first dose of trial treatment. Steroids for myeloma disease control must be stopped 14 days prior to the first dose of trial treatment.
• If previously treated with a lenalidomide-containing regimen, the participant is excluded if:
• Discontinued due to any adverse event related to prior lenalidomide (history of thromboembolism due to lenalidomide is allowed if participant is anticoagulated)
• If the participant was intolerant to lenalidomide.
• If the participant was refractory to any dose of lenalidomide. Refractory to lenalidomide is defined either:
• Participant had disease progression within 60 days after the last dose of lenalidomide; or Whose disease is non-responsive whilst on lenalidomide. Non-responsive disease is defined as either not achieving at least an minimal response (MR) or progressive disease (PD) whilst on lenalidomide.
• Any of the following prior treatments:
• Has had a prior allogenic stem cell transplant. Previous autologous stem cell transplantation is permitted greater than or equal to 3 months prior to the first dose of trial treatment.
• Previous therapy with pembrolizumab or has received prior therapy with an anti-PD-1, L1 or L2 inhibitor.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to the first dose of trial treatment or who has not recovered (i.e., less than or equal to Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• o Has had prior chemotherapy, targeted small molecule therapy, therapeutic radiation therapy within 2 weeks prior to the first dose of trial treatment or who has not recovered (i.e., less than or equal to Grade 1 or at baseline) from adverse events due to a previously administered agent. Participants with less than ore equal to Grade 2 neuropathy are an exception to this criterion and may participant in the trial.
• Treatment with plasmapheresis within 4 weeks prior to the first dose of trial treatment.
• Palliative radiotherapy for pain control and bisphosphonates are permitted

Sponsors & Collaborators

• University of Leeds: lead
• Myeloma UK: collaborator
• Karyopharm Therapeutics Inc: collaborator

Study Sites (4)

Queen Elizabeth Hospital

Birmingham, B15 2TH, United Kingdom

Location

University College Hospital

London, NW1 2BU, United Kingdom

Location

Guys and St Thomas NHS Foundation Trust

London, SE1 9RT, United Kingdom

Location

Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Cyclophosphamide; Lenalidomide; pembrolizumab

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Rakesh Popat

  University College, London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase I/II trial with an initial dose finding phase for cyclophosphamide and lenalidomide combined with fixed dose pembrolizumab

Study Record Dates

• First Submitted: May 24, 2017
• First Posted: June 19, 2017
• Study Start: August 1, 2017
• Primary Completion: August 1, 2017
• Study Completion: August 1, 2017
• Last Updated: August 24, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will not share

Locations

GB (4)