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Pembrolizumab, Belantamab and Dexamethasone in Refractory Multiple Myeloma.

Primary Purpose

Multiple Myeloma, Refractory

Status
Withdrawn
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Pembrolizumab
Belantamab mafodotin
Dexamethasone
Sponsored by
Hackensack Meridian Health
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma, Refractory

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Participants are eligible to be included in the study only if all of the following criteria apply:

  1. Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of multiple myeloma.
  2. Patients must have relapsed or must be considered refractory to all of the following:

    1. a proteasome inhibitor,
    2. an immunomodulating agent,
    3. a CD38-monoclonal antibody
    4. an autologous stem cell transplant
    5. CAR T-cell therapy (or ineligible)
  3. Patients must have more than 4 lines of prior therapy.
  4. Measurable disease, defined as one of the following:

    1. M-protein ≥ 0.5g/dL (0.3 g/dL or above if IgA subtype)
    2. Urine M-protein ≥ 200 mg/24hours
    3. Serum free light chain difference > 100 mg/L
    4. Biopsy proven plasmacytoma
    5. Bone marrow involvement >10%
  5. Life expectancy >3 months
  6. Eastern Cooperative Oncology Group (ECOG) Performance Score 0-1
  7. Adequate hepatic function within 28 days prior to Cycle 1 Day 1 (C1D1):

    1. Total bilirubin < 1.5 × upper limit of normal (ULN) (except patients with Gilbert's syndrome who must have a total bilirubin of < 3 × ULN), and
    2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) normal to <2 × ULN.
  8. Adequate renal function within 28 days prior to C1D1 as determined by estimated creatinine clearance of ≥ 30 mL/min, calculated using the Cockcroft and Gault formula (140 - Age) • Mass (kg)/ (72 • creatinine mg/dL); multiply by 0.85 if female (Cockcroft

1976). 9) Adequate hematopoietic function within 7 days prior to C1D1: total white blood cell (WBC) count ≥1500/mm3, absolute neutrophil count ≥1000/mm3, hemoglobin ≥8.5 g/dL and platelet count ≥30,000/mm3 (patients for whom <50% of bone marrow nucleated cells are plasma cells)

a. Patients receiving hematopoietic growth factor support, including erythropoietin, darbepoetin, granulocyte-colony stimulating factor (GCSF), granulocyte macrophage colony stimulating factor (GM-CSF), and platelet stimulators (eg, eltrombopag, romiplostim, or interleukin-11) must have a 2-week interval between growth factor support and the Screening assessments, but they may receive growth factor support during the study. b. Patients must have: i. At least a 2-week interval from the last red blood cell (RBC) transfusion prior to the Screening hemoglobin assessment, and ii. At least a 1-week interval from the last platelet transfusion prior to the Screening platelet assessment. However, patients may receive RBC and/or platelet transfusions as clinically indicated per institutional guidelines during the study. 10) Male and Female Participants: A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 4 months after the last dose of study treatment and refrain from donating sperm during this period. A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies:

  1. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
  2. A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 4 months after the last dose of study treatment. -

Exclusion Criteria:

  1. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study
  2. Any of the following laboratory abnormalities (unless there is >50% plasma cell involvement of the bone marrow):

    1. Absolute neutrophil count (ANC) < 1,000/μL
    2. Platelet count < 30,000/μL
    3. Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L)
    4. Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) or serum glutamic pyruvic transaminase (SGPT)/alanine aminotransferase (ALT) ≥ 2.5 x upper limit of normal (ULN)
    5. Serum total bilirubin, direct bilirubin, and alkaline phosphatase ≥ 1.5 x ULNf. Subjects with serious renal impairment ([CrCl] < 50 mL/min) or requiring dialysis would be excluded

    g. International Normalized Ratio (INR) of >1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants

  3. Subjects with a prior history of malignancies, other than Multiple Myeloma (MM), unless the subject has been free of the disease for ≥ 5 years with the exception of the following noninvasive malignancies:

    1. Basal cell carcinoma of the skin
    2. Squamous cell carcinoma of the skin
    3. Carcinoma in situ of the cervix
    4. Carcinoma in situ of the breast
    5. Incidental histological findings of prostate cancer such as T1a or T1b using the Tumor/Node/Metastasis (TNM) classification of malignant tumors or prostate cancer that is curative
  4. Subject has received a prior anti-BCMA therapy
  5. Subject has received prior systemic anti-cancer therapy including investigational agents within 3 weeks prior to study intervention
  6. Subject has received prior radiotherapy within 2 weeks of start of study intervention.

    Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease

  7. Subject has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed
  8. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 3 weeks prior to the first dose of study intervention
  9. Subject has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
  10. Subject has known active Central Nervous System (CNS) metastases and/or carcinomatous meningitis.

    Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 3 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.

  11. Subject has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
  12. Subject has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
  13. Subject has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
  14. Subject has an active infection requiring systemic therapy.
  15. Subject has a known history of Human Immunodeficiency Virus (HIV) infection.

    a. Note: No HIV testing is required unless mandated by local health authority.

  16. Subject has active Hepatitis B infection or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Note: no testing for Hepatitis C is required unless mandated by local health authority.
  17. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 4 months after the last dose of trial treatment.
  18. Subject has had an allogenic tissue/solid organ transplant
  19. Subject has uncontrolled ocular disease or keratopathy
  20. Subject has uncontrolled cardiovascular disease, specifically uncontrolled hypertension, recent Myocardial Infarction (within 4 months), NYHA Stage 3 or 4 congestive heart failure.
  21. Subject is a WOCBP who has a positive urine pregnancy test within 72 hours prior to first dose of study intervention (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  22. Contraindications to the other treatment regimens, as per local prescribing information
  23. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator. -

Sites / Locations

  • Lombardi Comprehensive Cancer Center, Georgetown University
  • John Theurer Cancer Center, Hackensack Meridian Health
  • Jersey Shore Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single-arm, multi-institution

Arm Description

Study Arm: Pembrolizumab 200 mg IV q3 weeks Belantamab 2.5 mg/kg IV q3 weeks. Dex 40 mg IV q3 weeks (20 mg if patient >75) Treatment will be administered on a 21-day cycle and will be continued until unacceptable toxicity or disease progression for up to 2 years (35 cycles)

Outcomes

Primary Outcome Measures

Overall Response Rate (ORR)
To evaluate the overall response rate for pembrolizumab, belantamab and dexamethasone (PBd) in patients with triple class refractory multiple myeloma.

Secondary Outcome Measures

Progression-Free Survival (PFS)
To assess rates of progression-free survival (PFS)
Overall Survival (OS)
To assess rates of overall survival (OS)
Time to next treatment
To assess rates of time to next treatment
Tolerability and Safety
To determine the tolerability and safety of the combination of pembrolizumab with belantamab and dexamethasone by rate of incidence of adverse events using National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE), v5.0

Full Information

First Posted
August 5, 2022
Last Updated
January 25, 2023
Sponsor
Hackensack Meridian Health
Collaborators
Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT05493618
Brief Title
Pembrolizumab, Belantamab and Dexamethasone in Refractory Multiple Myeloma.
Official Title
A Phase II Study of Pembrolizumab, Belantamab and Dexamethasone in Patients With Triple Class Refractory Multiple Myeloma.
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Withdrawn
Why Stopped
Study Drug Unavailability
Study Start Date
December 2022 (Anticipated)
Primary Completion Date
November 2025 (Anticipated)
Study Completion Date
November 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hackensack Meridian Health
Collaborators
Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a single arm, multi-institution (1) Hackensack Meridian Health at Hackensack, New Jersey (NJ) (2) Jersey Shore Medical Center, Neptune, NJ and (3) Georgetown/Lombardi Cancer Center) phase II study of the combination of pembrolizumab, belantamab, and dexamethasone in patients with triple class refractory multiple myeloma.
Detailed Description
This is a single arm, multi-institution (1) Hackensack Meridian Health at Hackensack, NJ (2) Jersey Shore Medical Center, Neptune, NJ and (3) Georgetown/Lombardi Cancer Center) phase II study of the combination of pembrolizumab, belantamab, and dexamethasone in patients with triple class refractory multiple myeloma. All institutions will share the same Institutional Review Board. Safety lead-in Cohort: After the first 10 patients are enrolled, an independent safety review committee will meet to review adverse events and toxicity and determine whether the trial will continue to enroll. Phase 2 portion: The remainder of patients will be enrolled using a Simon's - 2 stage design. The study will be conducted in compliance with the International Council for Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use/Good Clinical Practice (GCP) and applicable regulatory requirements.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma, Refractory

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Model Description
Safety lead-in Cohort: After the first 10 patients are enrolled, an independent safety review committee will meet to review adverse events and toxicity and determine whether the trial will continue to enroll. Phase 2 portion: The remainder of patients will be enrolled using a Simon's - 2 stage design.
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Single-arm, multi-institution
Arm Type
Experimental
Arm Description
Study Arm: Pembrolizumab 200 mg IV q3 weeks Belantamab 2.5 mg/kg IV q3 weeks. Dex 40 mg IV q3 weeks (20 mg if patient >75) Treatment will be administered on a 21-day cycle and will be continued until unacceptable toxicity or disease progression for up to 2 years (35 cycles)
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda
Intervention Description
Pembrolizumab 200 mg IV q3 weeks until unacceptable toxicity or disease progression for up to 2 years (35 cycles).
Intervention Type
Drug
Intervention Name(s)
Belantamab mafodotin
Other Intervention Name(s)
Blenrep
Intervention Description
Belantamab 2.5 mg/kg IV q3 weeks until unacceptable toxicity or disease progression for up to 2 years (35 cycles).
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Other Intervention Name(s)
Decadron
Intervention Description
Dexamethasone 40 mg IV q3 weeks (20 mg if patient >75) until unacceptable toxicity or disease progression for up to 2 years (35 cycles).
Primary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
To evaluate the overall response rate for pembrolizumab, belantamab and dexamethasone (PBd) in patients with triple class refractory multiple myeloma.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Progression-Free Survival (PFS)
Description
To assess rates of progression-free survival (PFS)
Time Frame
2 years
Title
Overall Survival (OS)
Description
To assess rates of overall survival (OS)
Time Frame
2 years
Title
Time to next treatment
Description
To assess rates of time to next treatment
Time Frame
2 years
Title
Tolerability and Safety
Description
To determine the tolerability and safety of the combination of pembrolizumab with belantamab and dexamethasone by rate of incidence of adverse events using National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE), v5.0
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participants are eligible to be included in the study only if all of the following criteria apply: Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of multiple myeloma. Patients must have relapsed or must be considered refractory to all of the following: a proteasome inhibitor, an immunomodulating agent, a CD38-monoclonal antibody an autologous stem cell transplant CAR T-cell therapy (or ineligible) Patients must have more than 4 lines of prior therapy. Measurable disease, defined as one of the following: M-protein ≥ 0.5g/dL (0.3 g/dL or above if IgA subtype) Urine M-protein ≥ 200 mg/24hours Serum free light chain difference > 100 mg/L Biopsy proven plasmacytoma Bone marrow involvement >10% Life expectancy >3 months Eastern Cooperative Oncology Group (ECOG) Performance Score 0-1 Adequate hepatic function within 28 days prior to Cycle 1 Day 1 (C1D1): Total bilirubin < 1.5 × upper limit of normal (ULN) (except patients with Gilbert's syndrome who must have a total bilirubin of < 3 × ULN), and Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) normal to <2 × ULN. Adequate renal function within 28 days prior to C1D1 as determined by estimated creatinine clearance of ≥ 30 mL/min, calculated using the Cockcroft and Gault formula (140 - Age) • Mass (kg)/ (72 • creatinine mg/dL); multiply by 0.85 if female (Cockcroft 1976). 9) Adequate hematopoietic function within 7 days prior to C1D1: total white blood cell (WBC) count ≥1500/mm3, absolute neutrophil count ≥1000/mm3, hemoglobin ≥8.5 g/dL and platelet count ≥30,000/mm3 (patients for whom <50% of bone marrow nucleated cells are plasma cells) a. Patients receiving hematopoietic growth factor support, including erythropoietin, darbepoetin, granulocyte-colony stimulating factor (GCSF), granulocyte macrophage colony stimulating factor (GM-CSF), and platelet stimulators (eg, eltrombopag, romiplostim, or interleukin-11) must have a 2-week interval between growth factor support and the Screening assessments, but they may receive growth factor support during the study. b. Patients must have: i. At least a 2-week interval from the last red blood cell (RBC) transfusion prior to the Screening hemoglobin assessment, and ii. At least a 1-week interval from the last platelet transfusion prior to the Screening platelet assessment. However, patients may receive RBC and/or platelet transfusions as clinically indicated per institutional guidelines during the study. 10) Male and Female Participants: A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 4 months after the last dose of study treatment and refrain from donating sperm during this period. A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 4 months after the last dose of study treatment. - Exclusion Criteria: Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study Any of the following laboratory abnormalities (unless there is >50% plasma cell involvement of the bone marrow): Absolute neutrophil count (ANC) < 1,000/μL Platelet count < 30,000/μL Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L) Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) or serum glutamic pyruvic transaminase (SGPT)/alanine aminotransferase (ALT) ≥ 2.5 x upper limit of normal (ULN) Serum total bilirubin, direct bilirubin, and alkaline phosphatase ≥ 1.5 x ULNf. Subjects with serious renal impairment ([CrCl] < 50 mL/min) or requiring dialysis would be excluded g. International Normalized Ratio (INR) of >1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants Subjects with a prior history of malignancies, other than Multiple Myeloma (MM), unless the subject has been free of the disease for ≥ 5 years with the exception of the following noninvasive malignancies: Basal cell carcinoma of the skin Squamous cell carcinoma of the skin Carcinoma in situ of the cervix Carcinoma in situ of the breast Incidental histological findings of prostate cancer such as T1a or T1b using the Tumor/Node/Metastasis (TNM) classification of malignant tumors or prostate cancer that is curative Subject has received a prior anti-BCMA therapy Subject has received prior systemic anti-cancer therapy including investigational agents within 3 weeks prior to study intervention Subject has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease Subject has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 3 weeks prior to the first dose of study intervention Subject has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. Subject has known active Central Nervous System (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 3 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention. Subject has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients. Subject has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed. Subject has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. Subject has an active infection requiring systemic therapy. Subject has a known history of Human Immunodeficiency Virus (HIV) infection. a. Note: No HIV testing is required unless mandated by local health authority. Subject has active Hepatitis B infection or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Note: no testing for Hepatitis C is required unless mandated by local health authority. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 4 months after the last dose of trial treatment. Subject has had an allogenic tissue/solid organ transplant Subject has uncontrolled ocular disease or keratopathy Subject has uncontrolled cardiovascular disease, specifically uncontrolled hypertension, recent Myocardial Infarction (within 4 months), NYHA Stage 3 or 4 congestive heart failure. Subject is a WOCBP who has a positive urine pregnancy test within 72 hours prior to first dose of study intervention (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Contraindications to the other treatment regimens, as per local prescribing information Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator. -
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Noa Biran, MD
Organizational Affiliation
Division of Hematology and Oncology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Lombardi Comprehensive Cancer Center, Georgetown University
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
John Theurer Cancer Center, Hackensack Meridian Health
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07410
Country
United States
Facility Name
Jersey Shore Medical Center
City
Neptune
State/Province
New Jersey
ZIP/Postal Code
07753
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
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Pembrolizumab, Belantamab and Dexamethasone in Refractory Multiple Myeloma.

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