A Study of Pembrolizumab Added to the Standard First-Line Therapy of Cyclophosphamide, Bortezomib, and Dexamethasone (CyBorD) for NDMM NTE

NCT04258683 | Withdrawn Phase 2 DMC

• 2 other identifiers: CMRG 006WINNIPEG
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Multiple Myeloma

Keywords

Hematologic Diseases; Pembrolizumab; Keytruda; Neoplasms; Plasma Cell; Cardiovascular Diseases; Immune System Diseases; Cyclophosphamide; Dexamethasone; Bortezomib; Anti-Inflammatory Agents; Bone Marrow

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

  For this combination of Pembrolizumab with standard CyBorD, determine the response rate according to IMWG criteria.

  36 months from study registration

Secondary Outcomes (1)

• Safety (adverse events) of Pembrolizumab in combination with CyBorD

  36 months from study registration

Study Arms (1)

Pembrolizumab with CyBorD

EXPERIMENTAL

This will be a single arm study of pembrolizumab with cyclophosphamide, bortezomib and dexamethasone (CyBorD).

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

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).

Also known as: Keytruda

Pembrolizumab with CyBorD

Eligibility Criteria

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

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Canadian Myeloma Research Group: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (4)

CancerCare Manitoba

Winnipeg, Manitoba, R3E0V9, Canada

Location

The Moncton Hospital

Moncton, New Brunswick, E1C6Z8, Canada

Location

CIUSSS de l'Estrie-CHUS

Sherbrooke, Quebec, J1H5N4, Canada

Location

Allan Blair Cancer Centre

Regina, Saskatchewan, S4T7T1, Canada

Location

MeSH Terms

Conditions

Multiple Myeloma; Hematologic Diseases; Neoplasms; Cardiovascular Diseases; Immune System Diseases

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Hemostatic Disorders; Vascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders

Study Design

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

Study Record Dates

• First Submitted: February 4, 2020
• First Posted: February 6, 2020
• Study Start: February 17, 2021
• Primary Completion: October 31, 2022
• Study Completion: October 31, 2022
• Last Updated: August 29, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (4)