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Multiple Myeloma Clinical Trials

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SLUHN 2015-108

A Phase III Study of Lenalidomide and Low-Dose Dexamethasone with or without Pembrolizumab (MK-3475) in Newly Diagnosed and Treatment-Naïve Multiple Myeloma (KEYNOTE 185)

  • Physician & Study Coordinator
  • Synopsis
  • Inclusion Criteria
  • Exclusion Criteria
  • Study Coordinator

    Jillian Timer, RN, BSN
    484-503-4156

    Jillian.Timer@sluhn.org
  • Treatment Agent: Pembrolizumab

    Synopsis: The purpose of this study is to test the safety, tolerability and anti-tumor activity of the research study drug, lenalidomide and low dose dexamethasone with or without pembrolizumab in subjects with newly diagnosed and treatment-naïve Multiple Myeloma measured by the rates of response to treatment, disease progression (disease getting worse) and survival.

    This is a research study to test a study drug, pembrolizumab, which has been approved for use in certain types of melanoma, however it has not been approved in any other cancers. The other drugs being used in this study, lenalidomide and dexamethasone, are available by prescription for Multiple Myeloma. Lenalidomide is marketed in the United States as REVLIMID®. Dexamethasone is marketed in the United States under a variety of brands including the brand Decadron®.

    • Be willing and able to provide written informed consent for the trial. The subject may also provide consent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research.
    • Be ≥ 18 years of age on day of signing informed consent.
    • Have a confirmed diagnosis of active multiple myeloma and measurable disease defined as:
      • Serum monoclonal protein (M-protein) levels ≥ 0.5 g/dL or
      • Urine monoclonal protein (M-protein) levels ≥200 mg/24-hours or
      • For subjects without measurable serum and urine M-protein levels, an abnormal serum free light chain ratio (FLC κ/λ) with involved FLC level ≥100 mg/L. (Normal serum FLC κ/λ value: 0.26 - 1.65).
      • Presence of CRAB features (hypercalcemia and/or renal impairment and/or anemia and/or bone disease; see Section 4.2.1.1 for the definition of CRAB features.
        • in the absence of CRAB features, subjects with any of the following biomarkers of malignancy: clonal bone morrow plasma cell percentage ≥60%, involved/uninvolved serum free light chain (FLC) ratio ≥ 100 mg/L or more than one focal bone lesion in MRI would also be eligible.
    • Must be ineligible to receive treatment with auto-SCT due to age (≥65 years old) or coexisting medical condition. Subjects < 65 years old who refuse auto-SCT are not eligible for this study.
    • Be able to provide, archival (≤60 days) or newly obtained bone marrow biopsy or aspirate material for disease assessment and biomarker analysis.
    • Must have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
    • Must demonstrate adequate organ function; all screening labs should be performed within 7 days of treatment initiation.
    • Female subjects of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication or per local requirements as per lenalidomide prescribing information. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
    • Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (see Section 5.7.2). Subjects of child-bearing potential are those who have not been surgically sterilized or are <45 years of age and have not been free from menses for >1 year.

    Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

    • Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

    Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

    • All subjects must agree to follow the regional requirements for lenalidomide counseling, pregnancy testing, and birth control; and be willing and able to comply with the regional requirements (for example, periodic pregnancy tests, safety labs, etc.).
    • Subject is able to swallow capsules and is able to take or tolerate oral medications on a continuous basis.
    • Has non-secretory or oligo-secretory myeloma, smoldering multiple myeloma (SMM), monoclonal gammopathy of undetermined significance (MGUS), plasma cell leukemia or Waldenström's macroglobulinemia.
    • Has a history of repeated infections, primary amyloidosis, hyperviscosity or POEMS syndrome.
    • Has a known history of immunosuppression or is receiving systemic steroid therapy or any other form of systemic immunosuppressive therapy within 7 days prior to the first dose of trial treatment. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor.

    Note: A short course of 40 mg of dexamethasone (≤4 days) or equivalent for emergency use is allowed after consultation with the Sponsor. In such cases, baseline mprotein values from serum and urine should be obtained before the short steroid course and be repeated prior to study drug administration on Cycle 1 Day 1.

    • Has had prior anti-myeloma therapy including but not limited to low-dose dexamethasone, IMiDs, proteasome inhibitors, chemotherapy, monoclonal antibody, auto-SCT or radiation therapy prior to entry in the study.

    Note: Major surgery is permitted, as long as the subject has recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.

    • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device prior to entry in the study.
    • Has undergone prior allogeneic hematopoetic stem cell transplantation within the last 5 years. (Subjects who have had a transplant greater than 5 years ago are eligible as long as there are no symptoms of Graft versus Host Disease (GVHD) and it was not performed as treatment for multiple myeloma).
    • Has known hypersensitivity to dexamethasone, lenalidomide, or pembrolizumab or any of its excipients.
    • Has peripheral neuropathy ≥ Grade 2.
    • Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
    • 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 (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
    • Has evidence of active, non-infectious pneumonitis.
    • Has an active infection requiring intravenous systemic therapy.
    • Has known psychiatric or substance abuse disorders that would interfere with compliance with the requirements of the trial.
    • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
    • Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
    • Has a known Human Immunodeficiency Virus (HIV), Hepatitis B (HBV), or Hepatitis C (HCV) infection.
    • Has received a live vaccine within 30 days prior to the first dose.
    • Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or sponsor staff directly involved with this trial, unless prospective IRB approval (by chair or designee) is given allowing exception to this criterion for a specific subject.

SLUHN 2015-92

A Phase III Study of Pomalidomide and Low Dose Dexamethasone with or without Pembrolizumab (MK-3475) in Refractory or Relapsed and Refractory Multiple Myeloma (Rrmm) (KEYNOTE 183)

  • Physician & Study Coordinator
  • Synopsis
  • Inclusion Criteria
  • Exclusion Criteria
  • Study Coordinator

    Carolyn Seith, MSPH
    484-503-4153 

    Carolyn.Seith@sluhn.org
  • Treatment Agent: Pembrolizumab

    Synopsis: The purpose of this study is to test the safety, tolerability and anti-tumor activity of the research study drug, pembrolizumab (MK-3475) with or without pomalidomide and low dose dexamethasone in subjects with refractory or relapsed and refractory Multiple Myeloma (rrMM) measured by the rates of response to treatment, disease progression (disease getting worse) and survival.

    This is a research study to test a study drug, pembrolizumab (MK-3475), that has been approved for use in certain types of melanoma; however, it has not been approved for Refractory or Relapsed and Refractory Multiple Myeloma (rrMM). Subjects in this study will be assigned to receive either the study drug, pembrolizumab in combination with Pomalidomide and Dexamethasone or Pomalidomide and Dexamethasone without Pembrolizumab.

    • Be willing and able to provide written informed consent for the trial. The subject may also provide consent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research.
    • Be ≥ 18 years of age on day of signing informed consent.
    • Has a confirmed diagnosis of active multiple myeloma and measurable disease defined as:
      • Serum monoclonal protein (M-protein) levels ≥ 0.5 g/dL or
      • Urine monoclonal protein (M-protein) levels ≥200 mg/24-hours or
      • for subjects without measurable serum and urine M-protein levels, an abnormal serum free light chain ratio (FLC κ/λ) with involved FLC level ≥100 mg/L. (Normal serum FLC κ/λ value: 0.26 - 1.65).
    • Must have undergone prior treatment with ≥ 2 treatment lines of anti-myeloma therapy and must have failed their last line of treatment defined as documented disease progression during or within 60 days of completing their last anti-myeloma therapy (refractory to last line of treatment).
    • Prior anti-myeloma treatments must have included an IMiD (lenalidomide or thalidomide) AND proteasome inhibitor (bortezomib or carfilzomib) alone or in combination and subject must have failed therapy with an IMiD OR proteasome inhibitor defined as one of the following:
      • Refractory: Documented progressive disease on or within 60 days of completing treatment with an IMiD and/or proteasome inhibitor OR
      • Relapsed and refractory: In case of prior response [≥ partial response (PR)] to an IMiD or proteasome inhibitor, subjects must have relapsed within 6 months after stopping treatment with an IMiD and/or proteasome inhibitor containing regimens
    • Be able to provide, archival (≤60 days) or newly obtained bone marrow biopsy or aspirate material for disease assessment and biomarker analysis at screening.
    • Must have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
    • Must demonstrate adequate organ function; all screening labs should be performed within 7 days prior to treatment initiation.
    • Female subjects of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication or per local requirements as per pomalidomide prescribing information. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
    • Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of child bearing potential are those who have not been surgically sterilized or are <45 years of age and have not been free from menses for >1 year. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
    • Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
    • All subjects must agree to follow the local requirements for pomalidomide counseling, pregnancy testing, and birth control; and be willing and able to comply with the local requirements (for example, periodic pregnancy tests, safety labs, etc.).
    • Subject is able to swallow capsules and is able to take or tolerate oral medications on a continuous basis.
    • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of treatment.
    • Subjects with non-secretory or oligo-secretory myeloma, smoldering multiple myeloma (SMM), monoclonal gammopathy of undetermined significance (MGUS), plasma cell leukemia or Waldenström's macroglobulinemia.
    • History of repeated infections, primary amyloidosis, hyperviscosity or POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
    • Has a known history of immunosuppression or is receiving systemic steroid therapy or any other form of systemic immunosuppressive therapy within 7 days prior to the first dose of trial treatment. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor.

    Note: A short course of 40 mg dexamethasone (≤4 days) or equivalent for emergency use is allowed after previous consultation with the Sponsor. In these cases, baseline m-protein values from serum and urine should be obtained before the short steroid course and be repeated prior to study drugs administration on Cycle 1 Day 1.

    • Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e. ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
    • Has had prior anti-myeloma therapy including but not limited to dexamethasone, IMiDs, proteasome inhibitors, chemotherapy or radiation therapy within 2 weeks prior to study Day 1 who has not recovered (i.e. ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.

    Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.

    Note: Toxicity that has not recovered to ≤ Grade 1 is allowed if it meets the inclusion requirements for laboratory parameters.

    • Has undergone prior allogeneic hematopoetic stem cell transplantation within the last 5 years. (Subjects who have had a transplant greater than 5 years ago are eligible as long as there are no symptoms of Graft versus Host Disease (GVHD).
    • Has received autologous stem cell transplant (auto-SCT) within 12 weeks before the first infusion or are planning for or are eligible for auto-SCT.
    • Treatment with plasmapheresis within 4 weeks prior the first dose of trial treatment.
    • Has known hypersensitivity to thalidomide, lenalidomide or dexamethasone.
    • Has received previous therapy with pomalidomide.
    • Subjects unable or unwilling to undergo thromboembolic prophylaxis including, as clinically indicated, aspirin, Coumadin (warfarin) or low-molecular weight heparin.
    • Subjects with peripheral neuropathy ≥ Grade 2.
    • Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
    • Has active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
    • Has evidence of active, non-infectious pneumonitis.
    • Has an active infection requiring intravenous systemic therapy.
    • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
    • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
    • Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
    • Has a known Human Immunodeficiency Virus (HIV), or known active Hepatitis B (HBV), or known active Hepatitis C (HCV) infection.
    • Has received a live vaccine within 30 days prior to first dose.
    • Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or sponsor staff directly involved with this trial.