Multiple MyelomaPhase 2NCT04258683
A Study of Pembrolizumab Added to the Standard First-Line Therapy of Cyclophosphamide, Bortezomib, and Dexamethasone (CyBorD) for NDMM NTE
A Phase 2 study testing Pembrolizumab in people with Multiple Myeloma, run by Canadian Myeloma Research Group at 4 sites in Canada.
Trial summary
This is a phase 2A multi-centre, open label, pilot study of pembrolizumab added to the standard first-line therapy of cyclophosphamide, bortezomib and dexamethasone (CyBorD) in newly diagnosed patients with multiple myeloma that are not eligible for autologous stem cell transplantation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 4 sitesCanada
- Study dates
- 17 Feb 2021to 31 Oct 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Must be able to understand and voluntarily sign an informed consent form (ICF).
- Must be ≥ 18 years of age at the time of signing the ICF.
- Newly diagnosed multiple myeloma (according to the IMWG diagnostic criteria) receiving standard of care CyBorD treatment and have not achieved at least VGPR or progressed after 2 cycles of treatment.
- Must have measurable disease according to the IMWG criteria as defined below:
- Serum M-protein ≥ 5 g/l
- Urine M-protein ≥ 200 mg/24 h
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- Serum free light chains (FLC) assay: Involved FLC level ≥ 100 mg/l and an abnormal serum free light chain ratio (< 0.26 or > 1.65)
- Must have Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
- Must not be eligible for consolidation with high dose chemotherapy and autologous stem cell transplantation (ASCT).
- Must not have any known congenital or acquired immune suppression.
- Must have negative serology for HIV, HBV and HCV.
- Male subject must agree to use contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period.
- Female subject is eligible to participate if she is not pregnant (see Appendix 3 of protocol), not breastfeeding, and at least one of the following conditions applies:
- Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 of protocol OR
- A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 of protocol during the treatment period and for at least 30 days after the last dose of study treatment.
- Must have adequate organ function as defined below. Specimens must be collected within 10 days prior to the start of study treatment.
- Absolute neutrophil count (ANC) ≥1500/µL
- Platelets ≥100 000/µL
- Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/La
- Creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR
- ≥30 mL/min for subject with creatinine levels >1.5 × institutional ULN
- Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for subjects with total bilirubin levels >1.5 × ULN
- AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for subjects with liver metastases)
- International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless subject is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
Who cannot join
- Prior exposure to Pembrolizumab (or other anti-PD-1, anti-PD-L1, or anti-PD-L2 agent; or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137)).
- Known allergies, hypersensitivity to mannitol, corticosteroids, monoclonal antibodies or human proteins, or their excipients (refer to the Pembrolizumab IB), or known sensitivity to mammalian-derived products
- History of prior allogeneic stem cell transplantation or solid organ transplantation that requires immunosuppressive therapy.
- History of prior autologous peripheral stem cell transplantation or bone marrow transplantation for any indication.
- Subject who is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. Subjects who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
- Myeloma with known CNS involvement, plasma cell leukemia or amyloidosis.
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- Chemotherapy or other anti-myeloma therapy other than three or less cycles of CyBorD. Prior bisphosphonates or other bone consolidation therapy is acceptable either if it was given for myeloma or for any other indication.
- Known congenital or acquired immune deficiency or ongoing chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immune suppressive therapy within 7 days prior to the first dose of study drug for any indication, excluding Dexamethasone or steroids given as part of myeloma treatment.
- Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
- Known chronic obstructive pulmonary disease (COPD), defined as a FEV1 <50% predicted value.
- Known moderate or severe persistent asthma within the last 2 years, or currently has uncontrolled asthma of any classification.
- History of or current uncontrolled cardiovascular disease including:
- Unstable angina, myocardial infarction, or known congestive heart failure Class III/IV (Appendix 5 of protocol) within the preceding 12 months.
- Transient ischemic attack within the preceding 3 months, pulmonary embolism within the preceding 2 months.
- Any of the following: sustained ventricular tachycardia, ventricular fibrillation, Torsades de Pointes, cardiac arrest, Mobitz II second degree heart block or third-degree heart block; known presence of dilated, hypertrophic, or restrictive cardiomyopathy.
- QTc prolongation as confirmed by ECG assessment at screening (QTc >470 milliseconds).
- Has an active infection requiring systemic therapy.
- Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
- Has received prior radiotherapy within 2 weeks of start of study treatment. Subjects must have recovered from all radiation-related toxicities
- Prior history of malignancies, other than MM, unless the subject has been free of the disease for 3 years or longer. Exceptions include the following:
- Basal or squamous cell carcinoma of the skin.
- Carcinoma in situ of the cervix or breast
- Adenocarcinoma of the prostate (TNM stage of T1a or T1b)
- Women who are pregnant, breastfeeding or planning to become pregnant while enrolled in this study, or within 90 days after the last dose of study medications. Male subject who plans to father a child while enrolled in this study, or within 120 days after the last dose of study medications.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
- Has a history or current evidence of any condition (i.e. uncontrolled diabetes, active or uncontrolled infection, acute diffuse pulmonary disease, pericardial disease, uncontrolled thyroid dysfunction), therapy or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator.
Trial locations and contacts
4 sites in 1 country.
Canada4 sites
The Moncton Hospital
Moncton, New Brunswick, E1C6Z8
Allan Blair Cancer Centre
Regina, Saskatchewan, S4T7T1
CIUSSS de l'Estrie-CHUS
Sherbrooke, Quebec, J1H5N4
CancerCare Manitoba
Winnipeg, Manitoba, R3E0V9
About this study
Official title: A Phase 2A Multi Centre, Open Label, Pilot Study Of Pembrolizumab Added to The Standard First-Line Therapy Of Cyclophosphamide, Bortezomib And Dexamethasone (CyBorD) In Newly Diagnosed Multiple Myeloma Patients Not Eligible For Autologous Stem Cell Transplantation
This is a phase 2A multi-centre, open label, pilot study of pembrolizumab added to the standard first-line therapy of cyclophosphamide, bortezomib and dexamethasone (CyBorD) in newly diagnosed patients with multiple myeloma that are not eligible for autologous stem cell transplantation.
Read the detailed description
This is a phase 2A, pilot study of pembrolizumab administered in combination with CyBorD in newly diagnosed, transplant ineligible multiple myeloma patients who achieve less than VGPR (according to IMWG criteria) after two cycles of treatment.
Newly diagnosed multiple myeloma patients will start their standard CyBorD treatment with the combination of cyclophosphamide administered at 300 mg/m2 orally, bortezomib administered at 1.5 mg/m2 subcutaneously, and dexamethasone administered orally at 40 mg, all given on days 1, 8, 15 and 22 of each 28-day cycle. Patients not progressing after 2 cycles of CyBorD treatment and achieving less than VGPR by IMWG criteria will be screened for this study. Subjects meeting the eligibility criteria will add pembrolizumab to their standard CyBorD treatment starting with cycle 4 day 1, which will be cycle one of this study treatment. Pembrolizumab in combination with CyBorD will be administered intravenously at 200 mg at day 1 of every 3-week cycle for 8 cycles (24 weeks). CyBorD will be discontinued after 24 weeks and Pembrolizumab will be administered as a single agent at the same dose for an additional 27 cycles (81 weeks).
- Conditions
- Multiple Myeloma
- Being tested
- Pembrolizumab
- Keywords
- Hematologic Diseases, Pembrolizumab, Keytruda, Neoplasms, Plasma Cell, Cardiovascular Diseases, Immune System Diseases, Cyclophosphamide, Dexamethasone, Bortezomib, Anti-Inflammatory Agents, Bone Marrow
- Medical subject headings
- Multiple Myeloma, Hematologic Diseases, Neoplasms, Cardiovascular Diseases, Immune System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called Keytruda
Patients not progressing after 2 cycles of CyBorD treatment and achieving less than VGPR by IMWG criteria will be screened to receive pembrolizumab intravenously at 200mg at day 1 of every 3-week cycle for 8 cycles (24 weeks) starting Cycle 4 of CyBorD. CyBorD will be discontinued after 24 weeks and pembrolizumab will be administered as a single agent at the same dose for an additional 27 cycles (81 weeks).
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab with CyBorD | Experimental | This will be a single arm study of pembrolizumab with cyclophosphamide, bortezomib and dexamethasone (CyBorD). Receives: Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate (ORR)
For this combination of Pembrolizumab with standard CyBorD, determine the response rate according to IMWG criteria.
Measured: 36 months from study registration
Secondary outcomes (1)
Safety (adverse events) of Pembrolizumab in combination with CyBorD
For this combination of Pembrolizumab with standard CyBorD, determine the incidence rates for adverse events using NCI CTCAE v5.0 grading. Generate a summary table for each term and body system, in addition to serious adverse events, subjects with related adverse events, subject deaths, and subjects who discontinue due to adverse events.
Measured: 36 months from study registration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2020
- Study start17 Feb 2021
- Primary completion31 Oct 2022
- Study completion31 Oct 2022
Why it stopped: Study terminated due to changing treatment landscape
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Canadian Myeloma Research Group
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04258683
- Sponsor's protocol ID
- CMRG 006
- Other IDs
- WINNIPEG
- Status last verified
- Aug 2023
- First submitted
- 4 Feb 2020
- Last updated
- 29 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2A Multi Centre, Open Label, Pilot Study Of Pembrolizumab Added to The Standard First-Line Therapy Of Cyclophosphamide, Bortezomib And Dexamethasone (CyBorD) In Newly Diagnosed Multiple Myeloma Patients Not Eligible For Autologous Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT04258683
- Acronym / sponsor ID
- CMRG 006
- Conditions
- Multiple Myeloma
- Keywords
- Hematologic Diseases, Pembrolizumab, Keytruda, Neoplasms, Plasma Cell, Cardiovascular Diseases, Immune System Diseases, Cyclophosphamide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study terminated due to changing treatment landscape
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Canadian Myeloma Research GroupUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 17 Feb 2021 (actual)
- Primary completion
- 31 Oct 2022 (actual)
- Study completion
- 31 Oct 2022 (actual)
- First posted
- 6 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase 2A multi-centre, open label, pilot study of pembrolizumab added to the standard first-line therapy of cyclophosphamide, bortezomib and dexamethasone (CyBorD) in newly diagnosed patients with multiple myeloma that are not eligible for autologous stem cell transplantation.
Detailed description
This is a phase 2A, pilot study of pembrolizumab administered in combination with CyBorD in newly diagnosed, transplant ineligible multiple myeloma patients who achieve less than VGPR (according to IMWG criteria) after two cycles of treatment.
Newly diagnosed multiple myeloma patients will start their standard CyBorD treatment with the combination of cyclophosphamide administered at 300 mg/m2 orally, bortezomib administered at 1.5 mg/m2 subcutaneously, and dexamethasone administered orally at 40 mg, all given on days 1, 8, 15 and 22 of each 28-day cycle. Patients not progressing after 2 cycles of CyBorD treatment and achieving less than VGPR by IMWG criteria will be screened for this study. Subjects meeting the eligibility criteria will add pembrolizumab to their standard CyBorD treatment starting with cycle 4 day 1, which will be cycle one of this study treatment. Pembrolizumab in combination with CyBorD will be administered intravenously at 200 mg at day 1 of every 3-week cycle for 8 cycles (24 weeks). CyBorD will be discontinued after 24 weeks and Pembrolizumab will be administered as a single agent at the same dose for an additional 27 cycles (81 weeks).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab with CyBorD | Experimental | Drug: PembrolizumabThis will be a single arm study of pembrolizumab with cyclophosphamide, bortezomib and dexamethasone (CyBorD). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Must be able to understand and voluntarily sign an informed consent form (ICF).
- Must be ≥ 18 years of age at the time of signing the ICF.
- Newly diagnosed multiple myeloma (according to the IMWG diagnostic criteria) receiving standard of care CyBorD treatment and have not achieved at least VGPR or progressed after 2 cycles of treatment.
- Must have measurable disease according to the IMWG criteria as defined below:
- Must have Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
Key exclusion criteria (26 listed)
- Prior exposure to Pembrolizumab (or other anti-PD-1, anti-PD-L1, or anti-PD-L2 agent; or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137)).
- Known allergies, hypersensitivity to mannitol, corticosteroids, monoclonal antibodies or human proteins, or their excipients (refer to the Pembrolizumab IB), or known sensitivity to mammalian-derived products
- History of prior allogeneic stem cell transplantation or solid organ transplantation that requires immunosuppressive therapy.
- History of prior autologous peripheral stem cell transplantation or bone marrow transplantation for any indication.
- Subject who is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. Subjects who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabAlso: KeytrudaPatients not progressing after 2 cycles of CyBorD treatment and achieving less than VGPR by IMWG criteria will be screened to receive pembrolizumab intravenously at 200mg at day 1 of every 3-week cycle for 8 cycles (24 weeks) starting Cycle 4 of CyBorD. CyBorD will be discontinued after 24 weeks and pembrolizumab will be administered as a single agent at the same dose for an additional 27 cycles (81 weeks). | Drug | Pembrolizumab with CyBorD |
Primary outcome
Overall response rate (ORR)
Time frame: 36 months from study registration
For this combination of Pembrolizumab with standard CyBorD, determine the response rate according to IMWG criteria.
1 secondary outcome
Safety (adverse events) of Pembrolizumab in combination with CyBorD
Time frame: 36 months from study registration
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab in people with Multiple Myeloma, run by Canadian Myeloma Research Group at 4 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 29 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall response rate (ORR) (time frame: 36 months from study registration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Aug 2023.