STEP I: Patients with monoclonal gammopathy of undetermined significance or asymptomatic multiple myeloma are not eligible
Histologically confirmed diagnosis of symptomatic multiple myeloma; relapsed disease is myeloma that has previously responded to prior therapy (MR or better) and subsequently progressed
Relapsed or relapsed/refractory multiple myeloma (MM) with progressive disease (PD) parameters according to International Myeloma Working Group (IMWG) criteria\r\n* Refractory is defined as experiencing less than minimal response to or PD within 60 days of the most recent line therapy\r\n* Relapsed is defined as patients requiring salvage therapy for PD who are not refractory to the most recent line of therapy
Diagnosis of multiple myeloma (MM) with relapsed and/or refractory disease. Participants must have received at least 3 prior lines of therapy. Participants must have previously received all of the following therapies and must be refractory to the last line of therapy prior to entering the study:
Participant has relapsed or refractory multiple myeloma with documented evidence of progression that occurred during or after the participant's last treatment regimen based on investigator's determination of International Myeloma Working Group (IMWG) criteria.
Participant has received previous multiple myeloma treatment as defined in the protocol for Part 1 and Part 2 of this study.
Treatment with anti-myeloma monoclonal antibodies within 6 weeks prior first dose.
Known meningeal involvement of multiple myeloma.
Males or females with multiple myeloma who have exhausted available standard therapies.
Anti-myeloma treatment within 2 weeks
Participants must have relapsed or refractory (R/R) multiple myeloma (MM) for which no established therapy for MM is appropriate and available or be intolerant to those established therapies
Patients with relapse/ refractory multiple myeloma
Histologically confirmed Multiple Myeloma prior to enrolment and randomization.
Histologically confirmed diagnosis of secretory multiple myeloma (must have measurable M protein in serum or urine) with at least one of the following:
primary refractory myeloma (PRMM): subjects who have never achieved the minimal response or better to prior therapy OR
Subjects with only plasmacytomas, plasma cell leukemia, monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), non-secretory myeloma or primarily amyloidosis.
Subjects who have previously participated in Merck pivotal trial NCT02576977: Study of Pomalidomide and Low Dose Dexamethasone With or Without Pembrolizumab (MK-3475) in Refractory or Relapsed and Refractory Multiple Myeloma (RRMM) (MK-3475-183/KEYNOTE-183).
A prior diagnosis of multiple myeloma with documented disease progression requiring further treatment at time of screening
Hematologic malignancies (including lymphoma, multiple myeloma)
INCLUSION CRITERIA: -Pathologically documented, multiple myeloma relapsed or refractory\n        disease after at least 2 lines of therapy, -Must be willing and able to undergo bone marrow\n        biopsy at screening, -Measurable disease per the IMWG response criteria, -Eastern\n        Cooperative Oncology Group (ECOG) performance status of ? 2, -Satisfactory hematological\n        function without transfusion or growth factor support, -Subjects should not have received\n        platelet transfusions for at least 1 week prior to screening, -Hemoglobin > 8 g/dL,\n        -Subjects may receive RBC transfusions or receive supportive care), -Other Inclusion\n        Criteria May Apply.\n\n        EXCLUSION CRITERIA: -Previously received an allogeneic stem cell transplant within 6 months\n        OR having received immunosuppressive therapy within the last three months OR having signs\n        or symptoms of acute or chronic graft-versus-host disease, -Autologous stem cell transplant\n        less than 90 days prior to study day 1, -Multiple myeloma with IgM subtype, -POEMS\n        syndrome, -Existing plasma cell leukemia, -Waldenstrom's macroglobulinemia, -Amyloidosis,\n        -Glucocorticoid therapy (prednisone > 30 mg/day or equivalent) within 7 days prior to\n        starting treatment, -Topical or inhaled corticosteroids are permitted, -Infection requiring\n        intravenous anti-infective treatments within 1 week of study enrollment (day 1), -Other\n        exclusion Criteria May Apply.
Potential subjects with evidence of progressive disease as per International Myeloma Working Group (IMWG) criteria
Patients must have a confirmed biopsy diagnosis of a multiple myeloma
Diagnosis of multiple myeloma (MM) and documentation of treatment
Histologically or cytologically confirmed multiple myeloma
Previous diagnosis of multiple myeloma based on standard criteria; tests need not be performed within 30 days of registration
Use of any myeloma-specific therapy within 21 days of the MILs collection
Myeloma specific therapy with a minimum of 3 cycles
Relapsed and relapsed/refractory multiple myeloma requiring systemic therapy
Waldenstrom’s macroglobulinemia or immunoglobulin M (IgM) myeloma
Cytopathologically or histologically confirmed dx of multiple myeloma
Ineligible disease sites include the following\r\n* Lymphoma\r\n* Leukemia\r\n* Multiple myeloma\r\n* Primary CNS\r\n* Peritoneal carcinomatosis \r\n* Colon cancer with resectable liver-only lesions
B-CLL or recurrent or refractory B-cell lymphoma (or other B-cell neoplasm) or multiple myeloma monoclonal for Kappa-light chain
Multiple myeloma diagnosed according to the International Myeloma Working Group (IMWG) diagnostic criteria
Diagnosis of MM requiring systemic therapy (per the International Myeloma Working Group [IMWG])
Low-risk smoldering multiple myeloma: must only present with 1 of the following criterion:\r\n* Monoclonal Protein >= 3 g/dL\r\n* >= 10% bone marrow plasma cells\r\n* FLC ratio < 0.125 or > 8
Any prior therapy for symptomatic multiple myeloma or smoldering multiple myeloma should also be excluded, including prior use of IMIDs, proteasome inhibitors, or CD138 inhibitors; prior therapy for smoldering multiple myeloma with agents that are not therapeutically active against MM is not an exclusion criterion
Is in need of additional myeloma therapy as determined by the investigator.
Has previously received at least 3 lines of myeloma therapy.
Diagnosis of advanced solid tumor cancer, lymphoma, or myeloma (no time restrictions or limitations) -OR- diagnosis of early stage solid tumor cancer, lymphoma, or myeloma <= 12 months prior to study enrollment
Malignant melanoma, papillary thyroid cancer, colorectal cancer, or hematologic malignancy including multiple myeloma
Patients with high risk multiple myeloma (criterion 3a above) in very good partial response (VGPR) or better at the time of enrollment with at most 1 prior progression within 18 months from initiation of systemic anti-myeloma therapy, which may include single or planned tandem autologous HSCT; or
Patients with standard risk multiple myeloma in VGPR or better at the time of enrollment with 1 prior progression within 18 months from a single or planned tandem autologous HSCT; or
Subjects must have documented evidence of progressive disease according to the IMWG uniform response criteria following the last multiple myeloma treatment.
IgA, IgD, IgE, IgM multiple myeloma: serum M-protein level ?0.5 g/dL (measured by PEP).
Multiple myeloma diagnosed according to standard criteria either currently or at the time of initial diagnosis
multiple myeloma as per IMWG 2014 definition
primary refractory myeloma
multiple myeloma
Adult male or female participants 18 years or older with a confirmed diagnosis of symptomatic newly diagnosed multiple myeloma (NDMM) according to standard criteria.
Multiple myeloma that has relapsed after, or was not responsive to, initial therapy.
Patient must have relapsed or refractory myeloma that fits or did fit International Myeloma Working Group (IMWG) diagnostic criteria for symptomatic myeloma (although new or worsening end organ damage is not required to be eligible) as defined below:\r\n* Presence of clonal bone marrow plasma cells\r\n* Presence of serum and/or urinary measurable monoclonal protein or light chains\r\n* Evidence of any end organ damage criteria listed below (at any time) attributed to the patient’s myeloma:\r\n** Hypercalcemia: serum calcium > 11.5 mg/dL or\r\n** Renal insufficiency: serum creatinine > 2 mg/dL\r\n** Anemia > 2 g/dL below the lower limit of normal or a hemoglobin value < 10 g/dL\r\n** Bone lesions: lytic lesions, severe osteopenia or pathologic fractures
Symptomatic multiple myeloma, International Staging System (ISS) stages I-III, within 12 months of starting therapy
Completion of induction therapy with very good partial response (VGPR), or better, by International Myeloma Working Group (IMWG) criteria
COHORT A: multiple myeloma
Prior cytotoxic chemotherapy or corticosteroids for the treatment of multiple myeloma; NOTE: prior corticosteroid use for the treatment of non-malignant disorders is permitted
Patients must have histologically or cytologically confirmed smoldering multiple myeloma confirmed by the Laboratory of Pathology, National Cancer Institute (NCI) or the Department of Laboratory Medicine, clinical center (CC), as needed, and based on the International Myeloma Working Group Criteria
Multiple myeloma beyond PR2: Patients with chromosome 13 abnormalities, first response lasting less than 6 months, or beta-2 microglobulin > 3 mg/L, may be considered for this protocol after initial therapy
Relapsed or refractory hematologic malignancy (lymphoma or multiple myeloma) that has progressed, or is currently progressing with standard anticancer therapy or for which no other approved therapy exist. Lymphoma patients must have failed at least 2 standard anticancer therapies, and multiple myeloma patients must have failed at least 3 standard anticancer therapies.
Relapsed, relapsed and refractory or refractory multiple myeloma patients who have received > 3 prior lines of therapy including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD28 monoclonal antibody
Received systemic treatment for multiple myeloma, including immunotherapy, within 14 days prior to initiation of study procedures
Diagnosis of relapsed, symptomatic multiple myeloma by International Myeloma Working Group (IMWG) diagnostic criteria for multiple myeloma
Myeloma disease that is refractory to ixazomib treatment
A prior diagnosis of multiple myeloma with documented disease progression in need of treatment at time of screening
Pathologically confirmed diagnosis of multiple myeloma who are transplant eligible and have received any prior induction therapy (with or without maintenance)
Any previous ASCT for multiple myeloma (MM)
Exhibiting clinical signs of meningeal involvement of multiple myeloma
Patients with multiple myeloma in first relapse (or who are primary refractory) following treatment with a bortezomib-containing regimen (excluding prior treatment with ixazomib)
Patient’s multiple myeloma cells are positive for CD28 or CD86 expression by flow cytometry or immunohistochemistry (in any proportion)
Patients with clinical relapse/progression as per the International Myeloma Working Group (IMWG) uniform criteria defined as one or more of the following criteria:\r\n* Development of new soft tissue plasmacytomas or bone lesions (osteoporotic fractures do not constitute progression)\r\n* Definite increase in the size of existing plasmacytomas or bone lesions. A definite increase is defined as a 50% (and >= 1 cm) increase as measured serially of the measurable lesion\r\n* Hypercalcemia (> 11 mg/dL)\r\n* Decrease in hemoglobin of >= 2 g/dL not related to therapy or other non-myeloma-related conditions\r\n* Rise in serum creatinine by 2 mg/dL or more from the start of the therapy and attributable to myeloma\r\n* Hyperviscosity related to serum paraprotein
Documented initial diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) diagnostic criteria
Participants with measurable multiple myeloma who have progressed on, or could not tolerate, all available established therapies
Patients must meet the criteria for symptomatic multiple myeloma prior to initiating systemic anti-myeloma treatment.
Patients with histologically-confirmed symptomatic multiple myeloma or AL amyloidosis undergoing autologous hematopoietic cell transplantation (HCT) with melphalan 140 or 200 mg/m^2
Evidence of a response (Partial response [PR] or better based on investigator's determination of response by international myeloma working group [IMWG] criteria) to at least 1 prior treatment regimen
Documented multiple myeloma as defined by the criteria below:
Multiple myeloma diagnosis according to the IMWG diagnostic criteria
International Staging System (ISS) stage I-III multiple myeloma that has progressive, relapsed, or refractory disease
Smoldering (asymptomatic) multiple myeloma
Histologically- or cytologically-confirmed relapsed or refractory multiple myeloma (MM) with measurable disease
Diagnosis of multiple myeloma refractory to or relapsed after >= 1 line of prior therapy (International Myeloma Working Group [IMWG] criteria)
Concurrent multiple myeloma (defined according to 2015 International Myeloma Working Group [IMWG] guidelines)
Multiple myeloma, solitary plasmacytoma, or primary malignant lesions in the index vertebra or bone
Diagnosis of newly diagnosed multiple myeloma with indication for initiation of therapy
Patients must have been previously diagnosed with histologically or cytologically confirmed symptomatic multiple myeloma, which require the presence of all three of the following International Myeloma Working Group criteria, except as noted:\r\n* Clonal bone marrow plasma cells >= 10%\r\n* A monoclonal protein in either serum or urine\r\n* Evidence of end-organ damage that can be attributed to the underlying plasma cell proliferative disorder (to include one of the following)\r\n** Hypercalcemia (corrected calcium > 2.75 mmol/L or 11.5 mg/dL); OR\r\n** Renal insufficiency attributable to myeloma (serum creatinine > 1.9 mg/dL); OR\r\n** Anemia; normochromic, normocytic with a hemoglobin value >= 2 g/dL below the lower limit of normal, or a hemoglobin or < 10 g/dL; OR\r\n** Bone lytic lesions (magnetic resonance imaging [MRI], computed tomography [CT] or positron emission tomography [PET]/CT with > 1 focal lesions >= 5 mm in size), severe osteopenia or pathologic fractures\r\n* Patients with a biopsy-proven plasmacytoma and either a serum or urine monoclonal protein will also be considered to have met the diagnostic criteria for multiple myeloma in the absence of clonal marrow plasmacytosis of >= 10%\r\n* Patient with bone marrow plasma cells of >= 60% or serum free light chain ratio of >= 100 will also be considered to have met the diagnostic criteria for multiple myeloma
Worsening urinary paraproteinemia will be considered in the context of International Myeloma Working Group (IMWG) disease response criteria on a monthly basis; any patient with urinary protein (otherwise unrelated to urinary myeloma associated monoclonal [M]-protein) with excretion > 3.5 g/day will be considered to have developed nephrotic-range proteinuria, and will be taken off study
Must have a confirmed diagnosis of multiple myeloma (MM) requiring therapy according to International Myeloma Working Group (IMWG) criteria.
Documented initial diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) diagnostic criteria
Measurable multiple myeloma that is relapsed or refractory to established therapies with known clinical benefit in relapsed/refractory multiple myeloma or be intolerant of those established multiple myeloma therapies, and a candidate for JNJ-64007957 treatment in the opinion of the treating physician. Prior lines of therapy must include a proteasome inhibitor and an immunomodulatory drug in any order during the course of treatment. Participants who could not tolerate a proteasome inhibitor or immunomodulatory drugs are allowed
Patients with a confirmed diagnosis of multiple myeloma who have received two or more lines of therapy including an IMiD and PI, and are relapsed and/or refractory to their most recent line of therapy. Patients who have received a prior autologous bone marrow transplant and otherwise meet the inclusion criteria are eligible for this study.
Histologically confirmed diagnosis of multiple myeloma
Received prior autologous stem cell transplantation as first line therapy for multiple myeloma with subsequent disease relapse/progression
Prior therapy for AL amyloidosis or multiple myeloma including medications that target CD38, with the exception of 160 mg dexamethasone (or equivalent corticosteroid) maximum exposure prior to randomization
Prior systemic anti-myeloma therapy within 14 days of Cycle 1 Day 1
FOR MULTIPLE MYELOMA ONLY: Obtained =< 14 days prior to registration: Platelet (PLT) >= 100,000/uL
FOR MULTIPLE MYELOMA ONLY: Obtained =< 14 days prior to registration: Hemoglobin >= 8.5 g/dl
MULTIPLE MYELOMA ONLYMultiple : >= 15% plasmas cells or plasmacytoma > 5 cm in largest diameter
Diagnosis\r\n* Phase I: confirmed diagnosis of relapsed or refractory multiple myeloma\r\n* Phase II: confirmed diagnosis of active multiple myeloma and must be newly diagnosed\r\n* NOTE: all tests for establishing disease status must be completed =< 28 days prior to registration
Relapsed multiple myeloma that is chemotherapy sensitive and has failed or ineligible for an autologous transplant
Diagnosis of symptomatic multiple myeloma as per current International Myeloma Working Group (IMWG) uniform criteria prior to initial treatment
Waldenstrom’s macroglobulinemia or IgM myeloma
Patients with poor prognosis multiple myeloma by cytogenetics del13, del 17p, t(4;14) or t(14;16) or hypodiploidy, with advanced disease (stage >= 2) and /or relapsed after autologous stem cell transplant
Patients must have histologically confirmed smoldering multiple myeloma (SMM) based on the following criteria; both criteria must be met: (a) serum monoclonal protein (IgG or IgA) >= 3 g/dL or urinary monoclonal protein >= 500 mg per 24 hours and/or clonal bone marrow plasma cells 10-60% (b) absence of myeloma defining events or amyloidosis
Additionally, patients must meet criteria for high risk of progression to multiple myeloma by PETHEMA CRITERIA (patients must have at least 2 risk factors present)\r\n* 1. >= 95% abnormal plasma cells/total plasma cells in bone marrow compartment (this is measured as a percentage of the total abnormal versus normal plasma cells in the bone marrow compartment using standard flow cytometry of the bone marrow aspirate; having >= 95% abnormal plasma cells/total plasma cells constitutes a risk factor for progression to multiple myeloma by PETHEMA criteria) \r\n* 2. Immunoparesis (this term refers to the patient having low uninvolved immunoglobulins in peripheral blood, for example if a patient has IgA smoldering multiple myeloma, then either having a low IgM and/or low IgG will qualify as a risk factor for progression to multiple myeloma)\r\n** 2 of 2 risk factors: high risk for progression at a rate of 72% at 5 years
Prior or concurrent systemic treatment for SMM; b) bisphosphonates are permitted, including pamidronate, zoledronic acid, alendronate, ibandronate, risedronate; c) treatment with corticosteroids is not permitted, unless the patient is on a stable chronic dose of inhaled steroids to treat respiratory diseases or on stable chronic steroid replacement therapy for endocrinology disorders; d) radiotherapy is not permitted, e) prior treatment for smoldering multiple myeloma with chemotherapy agents approved for the treatment of multiple myeloma or CD38 drugs is not permitted
Has received prior anti-myeloma therapy of any type
Patients must have either:\r\n* Symptomatic multiple myeloma who have responded to prior induction or salvage chemotherapy (i.e. chemosensitive disease): patients who are receiving high-dose melphalan and AHCT as part of their initial therapy require at least a partial response (PR) as defined by the International Myeloma Working Group uniform response criteria for MM; patients who are receiving high-dose melphalan and AHCT as part of salvage therapy require at least a minor response to their last line of therapy to document chemosensitive disease; there is no limit on the number of prior regimens received by the patient; OR\r\n* Light chain (AL) amyloidosis who may be newly diagnosed or previously treated
Histologic and serologic findings, reviewed at Memorial Sloan Kettering Cancer Center (MSKCC), confirming the diagnosis of multiple myeloma or AL amyloidosis; standard diagnostic criteria for multiple myeloma will be used, as per the International Myeloma Foundation consensus guidelines
At time of enrollment, subjects must be within 9 months of initiation of systemic therapy for multiple myeloma
Patients with histologically confirmed multiple myeloma
Received less than 4 lines of anti-myeloma therapy
Non-secretory multiple myeloma
Patient must have a diagnosis of symptomatic multiple myeloma, who relapses or is refractory after previous treatment with a proteasome inhibitor (bortezomib or carfilzomib) and an immunomodulatory agent (thalidomide, lenalidomide or pomalidomide)
Multiple myeloma: stage II or III, symptomatic, secretory multiple myeloma requiring treatment
RESEARCH SAMPLE COLLECTION: Histologically confirmed diagnosis of multiple myeloma
Histologically confirmed diagnosis of multiple myeloma
Meeting the criteria for symptomatic multiple myeloma (hypercalcemia renal [kidney] impairment, anemia, bone lesions \[CRAB]” criteria) before the initiation of systemic chemotherapy
Relapsed multiple myeloma that is chemotherapy sensitive and has failed or ineligible for an autologous transplant
Diagnosis of multiple myeloma undergoing planned autologous stem cell transplantation
Patient must have relapsed and symptomatic multiple myeloma
Patients who have received > 3 prior treatment regimens for multiple myeloma
Multiple myeloma beyond PR2: Patients with chromosome 13 abnormalities, first response lasting less than 6 months, or beta-2 microglobulin > 3 mg/L, may be considered for this protocol after initial therapy
Multiple myeloma progressive on salvage chemotherapy
Subjects with symptomatic multiple myeloma (MM) by International Myeloma Working Group (IMWG) criteria who are receiving or have completed induction chemotherapy, who have achieved at least a partial response (PR) on most recent therapy by IMWG criteria, and are eligible for auto-SCT for consolidation; a specific induction regimen is not dictated for this protocol, however, the induction regimen must not have contained melphalan (L-PAM, Alkeran)
Multiple myeloma specific:\r\n* Confirmed evidence of disease progression from immediately prior multiple myeloma (MM) therapy or refractory to the immediately prior treatment\r\n* Measurable disease M protein component in serum (at least 0.5 g/dL) and/or urine (if present), (>=0.2 g excreted in a 24 hour collection sample)\r\n* Subjects with free light chain only disease are excluded
Subjects must have a confirmed prior diagnosis of active MM as defined by the International Myeloma Working Group (IMWG) criteria
Histologies of myeloma or lymphoma
Primary tumor histology of lymphoma, leukemia, multiple myeloma or germ cell tumor
Histologically confirmed diagnosis of symptomatic multiple myeloma; (patients with multiple myeloma with secondary amyloidosis are eligible)
Received at least two cycles of any regimen as initial systemic therapy for multiple myeloma and are within 2-16 months of the first dose of initial therapy
Administration or planned administration of any other concomitant chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy which would be considered a treatment of multiple myeloma until day +28 post-transplant through discontinuation from study; patients may be on corticosteroids if they are being given for disorders other than multiple myeloma (e.g., adrenal insufficiency, rheumatoid arthritis, etc.)
Measurable relapsed or refractory myeloma as defined by the International Myeloma Working Group (IMWG) Consensus Criteria following treatment with at least 3 lines of therapy including with both a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or progressive myeloma that is refractory to a regimen containing both a PI and an IMiD.
Non-secretory multiple myeloma
Recent history of other (non multiple myeloma) cancer
Patients must have a diagnosis of multiple myeloma
Multiple myeloma\r\n* Relapse/progression after autologous HSCT\r\n* Plasma cell leukemia\r\n* Adverse cytogenetics: e.g. del(13q) or 11q translocation\r\n* At the time of enrollment, multiple myeloma (MM) must be in complete remission
Patients with newly diagnosed multiple myeloma who have at least a partial response after induction therapy based on the International Working Group (IWG) Uniform Response Criteria
PROCUREMENT: Diagnosis of myeloma after receiving at least one treatment regimen
Diagnosis of symptomatic multiple myeloma (MM)
Patients should have received the autologous SCT within 12 months of their diagnosis of myeloma to be eligible for the study
Primary tumor histology of lymphoma, leukemia, multiple myeloma or germ cell tumor
Symptomatic multiple myeloma, International Staging System (ISS) stage 1-3 with confirmed diagnosis of multiple myeloma at Memorial Sloan-Kettering Cancer Center (MSKCC)
Cytopathologically or histologically confirmed diagnosis of multiple myeloma
Symptomatic multiple myeloma of any subtype in any disease stage, providing the patient does not have smoldering myeloma, and otherwise met standard criteria (hypercalcemia, renal dysfunction, anemia and/or bone lesions – CRAB criteria) for induction therapy
Refractory or relapsed and refractory multiple myeloma
Diagnosis of multiple myeloma (MM) with deletion 17p (del17p) or monosomy 17 by fluorescence in situ hybridization (FISH) who have received at least one line of therapy
Recipients must have histopathologically confirmed diagnosis of multiple myeloma
Multiple myeloma with disease in the following categories:\r\n* Patients with relapsed multiple myeloma following autologous stem cell transplantation who have achieved at least partial response following additional chemotherapy\r\n* Patients with high risk cytogenetics at diagnosis must have achieved at least a partial response following autologous stem cell transplantation; patients must have complex karyotype, del17p, t4;14 and/or t14;16 by fluorescent in situ hybridization (FISH) and/or del13 by karyotyping
Multiple Myeloma (> CR2, > PR2) or after initial therapy if no prior PR: recent chemotherapy responsiveness
Multiple myeloma beyond PR2; patients with chromosome 13 abnormalities, first response lasting less than 6 months, or beta-2 microglobulin > 3 mg/L, may be considered for this protocol after initial therapy
Multiple myeloma beyond PR2: Patients with chromosome 13 abnormalities, first response lasting less than 6 months, or beta-2 microglobulin > 3 mg/L, may be considered for this protocol after initial therapy
Patients must have one of the following diagnoses of multiple myeloma (MM) or primary/secondary myelofibrosis (MF)
Patients must have a known diagnosis of multiple myeloma with evidence of measurable disease, as defined below:
Patient must have achieved MR or better with any anti-myeloma therapy (ie, primary refractory disease is not eligible).
Must have a diagnosis of a MM using current International Myeloma Working Group (IMWG) diagnostic criteria and have received 1 prior line of therapy.
Criteria 1 Relapsed or progressive multiple myeloma after last treatment
IgG multiple myeloma: serum monoclonal paraprotein (M-protein) level
IgA, IgD, IgE multiple myeloma: serum M-protein level ? 0.5 g/dL,
Criteria 2 Multiple myeloma of IgM subtype
Subject has histologically confirmed multiple myeloma that has never before been treated
Subject has previously been treated for multiple myeloma
Diagnosis of multiple myeloma as per International Myeloma Working Group (IMWG) uniform criteria
Relapsed/refractory multiple myeloma with progressive disease at study entry
Patient must have a diagnosis of multiple myeloma and have relapsed or relapsed/refractory disease.
Patient has smoldering multiple myeloma or monoclonal gammopathy of unknown significance (MGUS).
Patient received chemotherapy or other anti-cancer therapy that may be active against multiple myeloma within 3 weeks prior to the first dose of PRLX 93936.
Patient is taking any therapy concomitantly that may be active against multiple myeloma.
Multiple myeloma: stage II or III, symptomatic, secretory multiple myeloma requiring treatment
Patient with confirmed multiple myeloma requiring systemic therapy. All three criteria must be met:
Patient with multiple myeloma relapsing according to the International uniform response criteria for multiple myeloma (IMWG 2009/ revised Bladé criteria) to one previous line of treatment
Patient whose disease progressed during or within 60 days of bortezomib treatment or of any other Multiple Myeloma therapy
Confirmed relapsed or refractory multiple myeloma after at least two prior lines of therapy.
Multiple myeloma (Eligible patients must have quantifiable M-protein levels present in serum and/or urine)
Histologically or cytologically confirmed diagnosis of multiple myeloma that is relapsed or relapsed-and-refractory after at least 2 or more prior lines of therapy. Patients must have achieved at least minor response (MR) to at least one prior line of therapy
Progressive disease must have occurred either during or subsequent to the patient's last treatment for multiple myeloma prior to the current enrollment
Patient must have substantially recovered from clinically significant toxicities from prior therapies for multiple myeloma
Histologically or cytologically confirmed diagnosis of MM as defined according to International Myeloma Working Group (IMWG). The subject has undergone stem cell transplant or is considered transplant ineligible and has failed at least 3 prior lines of anti-myeloma treatments, including an anti-CD38 antibody (example [e.g.], daratumumab) alone or in combination, and is refractory to an Immunomodulatory drugs (IMiD) (that is [i.e.], lenalidomide or pomalidomide), and to a proteasome inhibitor (i.e., bortezomib, ixazomib or carfilzomib).
Have confirmed diagnosis of Multiple Myeloma as defined by the IMWG.
Documented diagnosis of multiple myeloma (MM) based on standard IMWG criteria.
Multiple myeloma meeting the following criteria:
Multiple myeloma with IgM subtype
Histologically confirmed diagnosis of multiple myeloma; (patients with multiple myeloma with secondary amyloidosis are eligible)
Received at least two cycles of any regimen as initial systemic therapy for multiple myeloma and are within 2-13 months of the first dose of initial therapy
Evidence of multiple myeloma (MM) disease progression any time prior to enrollment; progression from smoldering to active myeloma is not exclusionary
Patients with multiple myeloma in complete response (CR), partial remission (PR), very good partial remission (VGPR), or symptomatic stable disease (no evidence of progression) including patients with light chain multiple myeloma (MM) detected in the serum by free light chain assay.
Relapsed or refractory multiple myeloma. Participants with primary refractory myeloma only allowed in dose-escalation phase of the study.
Documented diagnosis of symptomatic multiple myeloma, as defined by the IMWG
For expansion cohorts only: Primary refractory multiple myeloma defined as disease that is non-responsive in participants who have never achieved a minimal response or better with any therapy
Subjects must have histologically confirmed diagnosis of multiple myeloma
Diagnosis of relapsed or relapsed and refractory multiple myeloma following at least 2 prior therapies which must include at least one immunomodulatory drug (e.g., thalidomide, lenalidomide or pomalidomide) and one proteasome inhibitor (e.g., bortezomib or carfilzomib). Patients must not be candidates for regimens known to provide clinical benefit.
Planned concurrent treatment for multiple myeloma other than bisphosphonates
Patient has been previously diagnosed with multiple myeloma (MM) based on standard International Myeloma Working Group (IMWG) criteria
Diagnosis of multiple myeloma according to International Myeloma Working Group criteria and one of the following:\r\n* Smoldering multiple myeloma (SMM)\r\n* Indolent multiple myeloma (IMM)\r\n* Newly diagnosed multiple myeloma (MM)\r\n* Note: patients with lytic disease and anemia are eligible
Patients must meet established criteria for the diagnosis of multiple myeloma
Patients with non-secretory multiple myeloma are not eligible
Diagnosis and previously untreated active multiple myeloma by International Myeloma Working Group (IMWG) diagnostic criteria for multiple myeloma
Prior cytotoxic chemotherapy or corticosteroids for the treatment of multiple myeloma\r\n* NOTE: Prior corticosteroid use for the treatment of non-malignant disorders is permitted
FOR PATIENTS WITH MULTIPLE MYELOMA (MM):
Diagnosis of multiple myeloma
Symptomatic multiple myeloma requiring treatment
Received at least two cycles of any regimen as initial systemic therapy for multiple myeloma and are within 2-12 months of the first dose of initial therapy
Evidence of multiple myeloma disease progression (as defined by International Myeloma Working Group [IMWG]) any time prior to ASCT
Smoldering multiple myeloma (MM) not requiring therapy
Multiple myeloma progressive on salvage chemotherapy
Has any type of amyloidosis, hyperviscosity, plasma cell leukemia, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, Waldenstrom's macroglobulinemia, non-secretory multiple myeloma or IgM myeloma
Histologically confirmed diagnosis of multiple myeloma
Received at least two cycles of any regimen as initial systemic therapy for multiple myeloma and are within 2-12 months of the first dose of initial therapy
MULTIPLE MYELOMA CRITERIA:
Patients must have received at least 3 different prior treatment regimens for multiple myeloma
Patients must carry a diagnosis of symptomatic multiple myeloma according to international myeloma working group criteria and have relapsed or refractory disease according to international uniform response criteria after at least two prior treatment regimens including a proteasome inhibitor and an immunomodulator (IMiD)
Radiosensitive primary tumor such as small cell lung cancer, germ cell tumors, lymphoma, leukemia, or multiple myeloma
Patients must have histologically or cytologically confirmed multiple myeloma not otherwise specified (NOS) (10028566)
A diagnosis of multiple myeloma (MM) and documentation of relapsed or relapse/refractory status following at least 2 prior lines of therapy
Patients must have a confirmed diagnosis of symptomatic multiple myeloma and must be currently relapsed or refractory; except where otherwise indicated below that assessment is required within 14 days, all tests for establishing disease status must be completed within 28 days prior to registration and documented on the Baseline Tumor Assessment Form for Multiple Myeloma
Symptomatic, previously untreated (with exception of corticosteroids) secretory myeloma
Any chemotherapy, immunotherapy, biologic, investigational, for treatment of multiple myeloma other than lenalidomide and dexamethasone
Previous systemic cancer therapy for myeloma
Diagnosis of non-secretory myeloma
MULTIPLE MYELOMA CRITERIA
Multiple myeloma\r\n* Primary treatment failure\r\n* Relapse after autologous SCT or for consolidation after autologous SCT\r\n* Non-CR after salvage regimen
Participants must have documented symptomatic myeloma, with organ damage related to myeloma as defined above with laboratory assessments
Prior glucocorticosteroid therapy for the treatment of multiple myeloma is not permitted
Confirmed diagnosis of active multiple myeloma and measurable disease.
Participant has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance (presence of serum M-protein <3 g/dL; absence of lytic bone lesions, anemia, hypercalcemia, and renal insufficiency related to the M-protein), or smoldering multiple myeloma (asymptomatic multiple myeloma with absence of related organ or tissue impairment end organ damage)
Diagnosis of MM requiring systemic therapy (per the International Myeloma Working Group [IMWG] ).
Has non-secretory multiple myeloma
Has a confirmed diagnosis of active multiple myeloma and measurable disease
Clinically overt multiple myeloma, according to the International Myeloma Working Group (IMWG) criteria with at least 1 of the following:
multiple myeloma (MM)
-  Documented relapsed or progressive Multiple Myeloma (MM) on or after any regimen or is refractory to the most recent line of therapy.
Measurable disease on Screening per International Myeloma Working Group (IMWG) criteria.
Subject must have documented diagnosis with previously untreated (for cohort C, the induction and consolidation treatment along with the first Autologous stem cell transplantation (ASCT) are allowed), symptomatic Multiple Myeloma (MM) as defined by the criteria below:
Any one or more of the following myeloma defining events:
Patient has been previously diagnosed with multiple myeloma (MM) based on standard criteria and currently requires treatment because MM has relapsed following a response, according to International Myeloma Working Group (IMWG) criteria.
Documented refractory or relapsed and refractory multiple myeloma
Has a confirmed diagnosis of active multiple myeloma and measurable disease.
Has non-secretory or oligosecretory multiple myeloma
Pathologically documented,multiple myeloma relapsed or refractory progressive disease after at least 3 lines of therapy for multiple myeloma. Prior therapeutic treatment or regimens must include proteasome inhibitors (e.g. bortezomib) and immunomodulatory drugs (e.g. lenalidomide).
Multiple myeloma with IgM subtype
Confirmed diagnosis of symptomatic multiple myeloma and measurable secretory disease
Diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, Waldenström's disease, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions
Prior or concurrent invasive malignancy (other than multiple myeloma) within 5 years of study start
Exhibiting clinical signs of meningeal involvement of multiple myeloma
Measurable disease per RECIST v1.1 for participants with solid malignancies. Disease-specific criteria for participants with prostate cancer, glioblastoma multiforme (GBM), malignant lymphoma, or multiple myeloma
Multiple myeloma (MM), limited to those patients for whom standard curative or palliative treatments do not exist or are no longer effective
Patient has a diagnosis of multiple myeloma with documented relapsed and/or relapsed-refractory disease
For Multiple Myeloma cohort
Have a documented diagnosis of multiple myeloma and have relapsed and refractory disease.
Primary refractory multiple myeloma defined as patients who have never achieved at least a minimal response (MR) with any treatment during the disease course.
Any anti-myeloma drug treatment within 14 days before randomization, including dexamethasone.
Participant has documented relapsed or progressive multiple myeloma on or after any regimen or who are refractory to the most recent line of therapy. Relapsed myeloma is defined as previously treated myeloma that progresses and requires initiation of salvage therapy, but does not meet the criteria for refractory myeloma. Refractory myeloma is defined as disease that is non responsive (failure to achieve minimal response or development of progressive disease [PD]) while on primary or salvage therapy, or progresses within 60 days of last therapy.
Histologically confirmed multiple myeloma
Four or less prior lines of systemic therapy for multiple myeloma
All subjects must have documented disease progression per IMWG criteria during or after their last anti-myeloma therapy.
Patients with multiple primary cancers
Participants proven to have multiple myeloma (MM) diagnosis according to the International Myeloma Working Group (IMWG) diagnostic criteria
Participant is exhibiting clinical signs of meningeal involvement of multiple myeloma
Newly diagnosed or relapsed multiple myeloma
For newly diagnosed multiple myeloma: multiple myeloma of IgM subtype
Diagnosis of smoldering multiple myeloma (SMM) for less than 5 years
Active multiple myeloma,requiring treatment as defined by the study protocol
Must have had documented multiple myeloma
Must have received at least 1 prior line of therapy for multiple myeloma
Must have had documented evidence of progressive disease as defined based on Investigator's determination of response of International Myeloma Working Group (IMWG) criteria on or after their last regimen
Has a history of malignancy (other than multiple myeloma) within 3 years before the date of randomization
Subjects of ? 18 years of age with histopathologically confirmed diagnosis of lymphoma or multiple myeloma that is refractory to or relapsed after at least 2 prior regimens.
Patients will be ineligible if they have advanced myeloma refractory to salvage chemotherapy regimens
Evidence of a response (partial response [PR] or better based on investigator's determination of response by International Myeloma Working Group [IMWG] criteria) to at least 1 prior treatment regimen
Documented measurable disease for multiple myeloma at screening as defined in protocol
Clinical signs of meningeal involvement of multiple myeloma
Patients who at initial diagnosis or later met the International Myeloma Working Group (IMWG) definition of active multiple myeloma requiring therapy (Appendix 3)
Patients must have histologically or cytologically confirmed smoldering multiple myeloma confirmed by Department of Pathology, based on the International Myeloma Working Group Criteria
Patients with a diagnosis of multiple myeloma (MM) per standard International Myeloma Working Group (IMWG) criteria
Prior or concurrent systemic treatment for SMM; a) bisphosphonates are permitted; b) treatment with corticosteroids is not permitted; c) radiotherapy is not permitted; d) prior treatment for smoldering multiple myeloma with chemotherapy agents approved for the treatment of multiple myeloma is not permitted
Participants must have a diagnosis of multiple myeloma (MM) according Revised International Myeloma Working Group diagnostic criteria:
Relapsed multiple myeloma
Refractory multiple myeloma defined as meeting 1 or more of the following:
At least 2 but no more than 3 prior therapies for multiple myeloma
Multiple myeloma of Immunoglobin M (IgM) subtype
Confirmed diagnosis of relapsed and/or refractory multiple myeloma (MM) according to International Myeloma Working Group guidelines (2003); refractory disease is defined as documented disease progression during or within 60 days after their most recent line of anti-myeloma therapy
Symptomatic multiple myeloma or any evidence of CRAB criteria including the new criteria for overt myeloma; any prior therapy for active myeloma should also be excluded; prior therapy for smoldering myeloma is not an exclusion criterion; bisphosphonates are not excluded
New diagnosis of multiple myeloma with no prior history of treatment (exceptions include corticosteroids, bisphosphonates, single agent cyclophosphamide, =< 21 days of the first cycle of a planned regimen)
History of previously treated smoldering myeloma
Participant has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma
Patients with relapsed and refractory multiple myeloma who have received at least 2 prior therapies, which must include lenalidomide and a proteasome inhibitor; patients must have disease refractory to the most recent therapy; refractory myeloma is defined as progressive disease during or within 60 days of last therapy; patients must have previously received or be ineligible for (or refused) autologous stem cell transplant
Adult male or female participants 18 years or older with a confirmed diagnosis of symptomatic multiple myeloma according to standard criteria.
Patients must have a history of symptomatic multiple myeloma according to the International Myeloma Working Group criteria (IMWG, 2003)
Patient has exquisitely radiosensitive histology, such as multiple myeloma, lymphoma, leukemia, or seminoma
Patients must have a diagnosis of relapsed or relapsed and refractory multiple myeloma with a minimum of one prior regimen and a maximum of 5 prior regimens
Must have documented multiple myeloma and measurable disease
Must have received at least 1 prior line of therapy for multiple myeloma and achieved a response (partial response or better) to at least one prior regimen
Must have documented evidence of progressive disease as defined by the International Myeloma Working Group criteria on or after their last regimen
Multiple myeloma that is primary refractory or relapsed and refractory after at least 2 lines of standard for multiple myeloma including: a. > 2 consecutive cycles of both bortezomib and lenalidomide or thalidomide (alone or in combination) i. Patients who received bortezomib as their last therapy who were not refractory but developed bortezomib intolerance, as defined by the development of Grade 2 peripheral neuropathy with pain or > Grade 3 peripheral neuropathy after ? 2 consecutive cycles, are eligible b. Adequate alkylator therapy defined as: i. High-dose melphalan or other alkylating agent as conditioning for autologous or allogeneic stem cell transplant (SCT), or ii. ? 6 cycles of induction therapy, or iii. PD after ? 2 cycles
Must have a documented diagnosis of multiple myeloma and have relapsed-and-refractory disease. Patients must have received at least 2 lines of prior therapies. Patients must have relapsed after having achieved at least stable disease (SD) for at least one cycle of treatment to at least one prior regimen and then developed progressive disease (PD). Patients must also have documented evidence of PD during or within 60 days (measured from the end of the last cycle) of completing treatment with the last anti-myeloma drug regimen used just prior to study entry (refractory disease)
Must have measurable levels of myeloma paraprotein in serum (? 0.5 g/dL) or urine (? 0.2 g/24 hours)
Participants must have a previous diagnosis of MM, according to International Myeloma Foundation 2003 diagnostic criteria
Histologic confirmation of multiple myeloma by the enrolling institution
Symptomatic myeloma that has progressed/relapsed after 1 to 3 prior lines of therapy
Multiple Myeloma according to the International Myeloma Working Group definition (2) i.e.: clonal bone marrow plasma cells >= 10% or biopsy-proven bony or extramedullary plasmacytoma and any one or more of the following myeloma defining events and/or one or more of the biomarkers for malignancy at the time of diagnosis:\r\n* Myeloma defining events:\r\n** Hypercalcemia: serum calcium > 0.25 mmol/L (> 1 mg/dL) higher than the upper limit of normal or > 2.75 mmol/L (> 11 mg/dL)\r\n** Renal insufficiency: creatinine clearance < 40 mL per minimum (min) or serum creatinine > 177 umol/L (> 2 mg/dL)\r\n** Anemia: hemoglobin value of > 20 g/L below the lower limit of normal, or a hemoglobin value < 100 g/L\r\n** Bone lesions: one or more osteolytic lesions on skeletal radiography, computed tomography (CT), or positron emission tomography (PET)-CT\r\n* Biomarkers of malignancy:\r\n** Clonal bone marrow plasma cell percentage >= 60%\r\n** Involved: uninvolved serum free light chain ratio >= 100\r\n** > 1 focal lesions on magnetic resonance imaging (MRI) studies
Patients with a diagnosis of multiple myeloma (MM) not achieving a VGPR or better to the most recent therapy.
Patients receiving > 1 cycle of prior treatment or concurrent systemic treatment for multiple myeloma\r\n* Treatment of hypercalcemia or spinal cord compression or aggressively progressing myeloma with current or prior corticosteroids is permitted\r\n* Bisphosphonates are permitted\r\n* Concurrent or prior treatment with corticosteroids for indications other than multiple myeloma is permitted\r\n* Prior treatment with radiotherapy is permitted\r\n* Prior treatment for smoldering myeloma is permitted with a washout period of 2 weeks from last dose; smoldering patients previously treated with carfilzomib are excluded\r\n* Patients with measurable disease who received up to one cycle of any therapy within 60 days with a washout period of 2 weeks from last dose (on a trial or outside a trial) are eligible
Relapsed or refractory multiple myeloma and has already received =< 4 standard treatment regimens; note: induction, transplant, consolidation, and maintenance is considered one regimen
Patients must have a diagnosis of myeloma (see Appendix A for diagnostic criteria).
Patients must have progressive or active disease following prior therapy for their myeloma which:
Male or female patients 18 years or older diagnosed with Multiple Myeloma according to standard criteria who have not received prior treatment
Prior treatment for multiple myeloma with either standard of care treatment or investigational regimen
Participants must have had a diagnosis of symptomatic multiple myeloma (MM), MM + amyloidosis, or POEMS (osteosclerotic myeloma: polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) requiring treatment; participants with a previous history of smoldering myeloma will be eligible if there is evidence of progressive disease requiring chemotherapy; note that study participants do not need to have active disease at the time of study entry, as participants may have received up to 12 months of prior chemotherapy, which might have induced a response
Diagnosis of multiple myeloma with measureable disease
Patients requiring therapy who have relapsed and/or are refractory to their last therapy and have been treated with at least 1, but not more than 5 lines of multiple myeloma therapy.
Newly diagnosed, myeloma requiring systemic chemotherapy as per International Myeloma Working Group (IMWG) uniform criteria:\r\n* Prior treatment of hypercalcemia or spinal cord compression or active and/or aggressively progressing myeloma with corticosteroids or lenalidomide or bortezomib-based regimens does not disqualify the patient (the treatment dose should not exceed the equivalent of 160 mg of dexamethasone in a 4 week period or not more than 1 cycle)\r\n* Bisphosphonates are permitted
Patients must have histologically or cytologically confirmed relapsed multiple myeloma as defined by the International Myeloma Working Group (IMWG)
Must have documented diagnosis of multiple myeloma and have measureable disease by serum and urine protein electrophoresis.
Must have had at least 1 but no greater than 3 prior anti-myeloma regimens.
Must have documented disease progression during or after their last anti-myeloma therapy.
Non-secretory multiple myeloma.
Meets criteria for symptomatic multiple myeloma, defined as:\r\n* >= 10% monoclonal plasma cells in the marrow AND ANY OF THE FOLLOWING:\r\n** Biopsy-confirmed plasmacytoma\r\n** Lytic bone lesion(s)\r\n** Hypercalcemia without other explanation
Symptomatic multiple myeloma;
Diagnosis of active Multiple Myeloma according to the International Myeloma Working Group (IMWG) diagnostic criteria
Relapsed or relapsed/refractory progressive Multiple Myeloma
Patient with radiosensitive histologies (lymphoma, multiple myeloma, small cell carcinomas, germ cell tumors)
(Part 1) Have relapsed multiple myeloma after receiving a minimum of 2 and a maximum of 4 prior lines of therapy and be eligible for treatment with lenalidomide and dexamethasone (Len/Dex)
(Part 2) Have received at least 1 prior line of therapy for multiple myeloma
Recovered from the effects of any prior systemic therapy or radiotherapy for Multiple Myeloma
Multiple myeloma diagnosed according to standard criteria either currently or at the time of initial diagnosis. NOTE: The initial diagnosis must have been symptomatic multiple myeloma, although the relapsed disease did not need to be symptomatic.
Participants with relapsed and/or refractory multiple myeloma (RRMM) who had received 1 to 3 prior therapies. NOTE: population included the following 3 categories of participants:
Diagnosis of smoldering multiple myeloma (SMM) for <4 years
Having symptomatic multiple myeloma, defined by any of the following (if due to myeloma): lytic bone lesions, severe osteopenia (low bone density), pathologic fractures, hypercalcemia (too much calcium in the blood), kidney insufficiency; symptomatic hyperviscosity of the blood, or recurrent serious bacterial infections such as pneumonia
Confirmed diagnosis of multiple myeloma that is relapsed and/or refractory for which no curative option exists.
Patient must not have been previously treated with any prior systemic therapy for the treatment of active multiple myeloma\r\n* Prior treatment of hypercalcemia or spinal cord compression with corticosteroids does not disqualify the patient (the dose should not exceed the equivalent of 320 mg of dexamethasone in a 2 week period)\r\n* Bisphosphonates are permitted\r\n* Prior therapy for smoldering myeloma is permitted
Patients with relapsed multiple myeloma who have already received one or more standard treatment regimens
Previously diagnosed with multiple myeloma.
Patients meeting the criteria for symptomatic multiple myeloma (MM):\r\n* Lytic lesions on skeletal survey or\r\n* Plasmacytoma\r\nPatients meeting International Myeloma Working Group definition of symptomatic myeloma with symptoms only related to associated amyloidosis who would otherwise only meet the criteria for smoldering MM are potentially eligible
A histologically established diagnosis of multiple myeloma with evidence of relapse or refractory disease.
Refractory or relapsed multiple myeloma
Confirmed diagnosis of multiple myeloma
Patient must have multiple myeloma that has either relapsed or has high risk cytogenetics
Patients receiving > 1 cycle of prior treatment or concurrent systemic treatment for multiple myeloma\r\n* Treatment of hypercalcemia or spinal cord compression or aggressively progressing myeloma with current or prior corticosteroids is permitted\r\n* Bisphosphonates are permitted\r\n* Concurrent or prior treatment with corticosteroids for indications other than multiple myeloma is permitted\r\n* Prior treatment with radiotherapy is permitted\r\n* Prior treatment for smoldering myeloma is permitted with a washout period of 4 weeks from last dose; smoldering patients previously treated with carfilzomib are excluded\r\n* Patients with measurable disease who received up to one cycle of any therapy within 60 days with a washout period of 4 weeks from last dose (on a trial or outside a trial) are eligible
MSKCC confirmed diagnosis of multiple myeloma that has relapsed or is resistant after therapy with at least one immunomodulatory drug (i.e. lenalidomide, thalidomide) and at least one proteasome inhibitor
Patients with multiple myeloma who are potential candidates for high dose chemotherapy with stem cell rescue
The primary tumor is small-cell lung cancer, lymphoma, leukemia, or multiple myeloma
Must have received 1-5 prior therapies for their myeloma and have relapsed or refractory multiple myeloma; prior therapy with bortezomib is allowed as long as they were not refractory to bortezomib
Histologic and serologic findings from Memorial Sloan-Kettering Cancer Center (MSKCC) confirming the diagnosis of multiple myeloma; standard diagnostic criteria for multiple myeloma will be used, as per the revised International Myeloma Working Group diagnostic criteria
Patients may have received 1 cycle of prior therapy with dexamethasone for multiple myeloma
Prior treatment for myeloma except for one cycle of dexamethasone
Multiple myeloma\r\n* Relapse/progression after autologous HSCT\r\n* Plasma cell leukemia\r\n* Adverse cytogenetics: del(13q) or 11q translocation
Multiple myeloma: stage II or III, symptomatic, secretory multiple myeloma requiring treatment
Any myeloma directed therapy within 12 weeks of registration including plasmapheresis or transfusion
Meets diagnostic criteria for symptomatic multiple myeloma
Lesions due to hematologic malignancy (e.g. multiple myeloma at site of the index vertebra (e),
Symptomatic multiple myeloma by International Myeloma Working Group (IMWG) criteria according to the most recent updated version (International Myeloma Workshop [IMW] meeting in Paris 2011)
Must have a documented diagnosis of relapsed and refractory multiple myeloma defined by the International Myeloma Working Group (IMWG) criteria.
Patients with plasma cell myeloma treated with induction therapy or re-induction therapy, who at the time of study enrollment have documented evidence of stable disease response or better according to International Myeloma Workshop Consensus Panel
Patients with progressive or refractory plasma cell myeloma, as defined by International Myeloma Workshop Consensus Panel criteria
Diagnosed with previously treated multiple myeloma.
Histologically or cytologically confirmed diagnosis of multiple myeloma that has progressed despite at least one line of standard therapy
Meets the International Myeloma Working Group (IMWG) definition of Multiple Myeloma
Treatment Group C (TGC): Multiple myeloma
Confirmed diagnosis of multiple myeloma with a BRAF V600 mutation
Must have received at least one prior systemic therapy for the treatment of multiple myeloma
Must have relapsed and/or refractory multiple myeloma with measurable disease
Melanoma, papillary thyroid cancer or hematological malignancies (with the exception of multiple myeloma)
Multiple myeloma: solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia
Patients previously diagnosed with multiple myeloma
Patients must have relapsed or relapsed and refractory multiple myeloma (MM) after at least three but not more than six prior therapeutic regimens for MM, including induction therapy and stem cell transplant in candidate patients, which will be considered as only one regimen.
Diagnosis of multiple myeloma
No more than six months’ worth of multiple myeloma chemotherapy is allowed (from the date of the start of the induction therapy)
Diagnosis of relapsed multiple myeloma
For more information regarding BMS clinical trial participation, please visit\n        www.BMSStudyConnect.com\n\n        Inclusion Criteria:\n\n          -  Subjects must have histological confirmation of multiple myeloma with measurable\n             disease (per International Myeloma Working Group (IMWG) criteria):\n\n               -  Relapsed/refractory multiple myeloma, subjects who are post autologous transplant\n                  and have achieved very good partial response (VGPR) or complete response (nCR)\n                  with minimal residual disease (MRD)
Patients with confirmed multiple myeloma whose treatment history must include all of the following:
Measurable multiple myeloma disease, defined as meeting at least one of the following criteria within 14 days prior to first dose of study drug:
Primary amyloidosis (amyloidosis associated with multiple myeloma is allowed).
Patients with relapsed/refractory multiple myeloma based on standard criteria
Confirmed multiple myeloma with measurable disease.
Disease refractory to last myeloma regimen.
Primary amyloidosis (amyloidosis associated with multiple myeloma is allowed).
Patients with any hematologic malignancy. This includes leukemia (any form), lymphoma, and multiple myeloma.
Memorial Sloan-Kettering Cancer Center (MSKCC) confirmed diagnosis of multiple myeloma that has relapsed or is resistant after therapy with at least one immunomodulatory drug (i.e. lenalidomide, thalidomide) and at least one proteasome inhibitor
Patients with multiple myeloma (MM) diagnosed according to standard criteria or patients with a diagnosis of an advanced malignant solid tumor for which standard, curative, or life prolonging treatment does not exist or is no longer effective. Patients with multiple myeloma must have had at least 1 prior therapy
Patients with relapsed/refractory multiple myeloma after at least 1 prior therapy
Newly diagnosed symptomatic multiple myeloma (per International Myeloma Working Group [IMWG] diagnostic criteria)
No prior treatment for multiple myeloma
Multiple myeloma of IgM (immunoglobulin M) subtype
Multiple myeloma
Willing to undergo pre-dose core needle tumor biopsies or bone marrow aspirate for subjects with multiple myeloma.
Relapsed or refractory Multiple Myeloma (MM) a. Treated with at least 1 prior regimen for myeloma
Diagnosis of symptomatic MM as defined by the International Myeloma Working Group (IMWG) :
Patients with relapsed multiple myeloma who have already received one or more standard treatment regimens
Elevated Free Light Chain as per the International Myeloma Working Group (IMWG) criteria
Patients must have a history of symptomatic multiple myeloma according to the International Myeloma Working Group criteria (IMWG, 2003), as defined as the following three criteria:\r\n* Clonal plasma cells > 10% on bone marrow biopsy\r\n* A monoclonal protein (paraprotein) in either serum or urine (except in cases of non-secretory myeloma)\r\n* Evidence of end-organ damage felt related to the plasma cell disorder (related organ or tissue impairment, ROTI, commonly referred to by the acronym \calcium, renal failure, anemia, and bone lesions [CRAB]\):\r\n* Hypercalcemia serum calcium (Ca) >= 11.5 mg/dL or\r\n* Renal insufficiency attributable to myeloma; serum creatinine > 2mg/dL\r\n* Anemia: Normochromic, normocytic with a hemoglobin value > 2g/dL below the lower limit of normal or a hemoglobin < 10 g/dL\r\n* Bone lesions (lytic lesions, severe osteopenia or pathologic fractures)
Patients with relapsed or refractory myeloma who have had >= 3 lines of prior therapy
Multiple myeloma with relapsing or progressing disease at study entry.
Patients must have evaluable multiple myeloma with, at least one of the following (assessed within 21 days prior to randomization):
Multiple Myeloma of IgM subtype.
Diagnosis of relapsed or refractory multiple myeloma (MM) and documentation of at least 1 prior therapy; there is no maximum number of prior regimens
Multiple myeloma (MM)
Subjects with Multiple Myeloma (MM) and renal function fitting one of three categories:
Symptomatic multiple myeloma or asymptomatic myeloma with myeloma-related organ damage diagnosed according to standard criteria
Prior systemic therapy for multiple myeloma, including investigational drugs (prior treatment with corticosteroids or localized radiation therapy dose not disqualify the patient)
Is diagnosed with symptomatic multiple myeloma or asymptomatic myeloma with myeloma-related organ damage according to standard criteria
Has prior systemic therapy for multiple myeloma, including investigational drugs (prior treatment with corticosteroids or localized radiation therapy dose not disqualify the participantt)
Patient has relapsed or relapsed/refractory MM with measurable disease parameters according to the International Myeloma Working Group (IMWG) Criteria
Subjects must have documented diagnosis of multiple myeloma and have measurable disease
Part A: Have histological or cytological evidence of cancer (solid tumor, lymphoma, or multiple myeloma) that is advanced and/or metastatic and an appropriate candidate for experimental therapy
Documentation of at least one line of prior myeloma therapy now with relapsed or refractory disease requiring re-treatment
Use of any anti-myeloma drug therapy within 14 days of initiation of study drug treatment excluding corticosteroids if given for an indication other than myeloma; note: bisphosphonates are not considered anti-myeloma drugs
Relapsed multiple myeloma. At least ?1 line of therapy and progressed after ?1 prior therapy
Multiple myeloma of IgM subtype, POEMS, plasma cell leukemia
Multiple myeloma of IgM subtype, POEMS, plasma cell leukemia
Symptomatic multiple myeloma
Prior treatment with at least one, but no more than three, regimens for multiple myeloma
Waldenström's macroglobulinemia or IgM myeloma
Patients with poor prognosis multiple myeloma by cytogenetics (del13, del 17p, t(1;14) or t(14;16) or hypodiploidy, with advanced disease (stage >= 2) and/or relapsed after autologous stem cell transplant
Age 18 years or older with a confirmed diagnosis of multiple myeloma (MM) and documentation of one to three prior therapies.
Previously untreated, symptomatic multiple myeloma as defined by the 3 criteria below:
Prior history of malignancies, other than multiple myeloma, unless the patient has been free of the disease for ? 3 years. Exceptions include the following:
1 A variety of other types of end organ dysfunctions can occasionally occur and lead to a need for therapy. Such dysfunction is sufficient to support classification as myeloma if proven to be myeloma-related.
Patients must have a diagnosis of active multiple myeloma
Clinically overt multiple myeloma (i.e. original hypercalcemia, renal failure, anemia, bone lesions [CRAB] criteria); Note: extent of marrow plasmacytosis is not prohibitive
Patients must have a definitive diagnosis of multiple myeloma (using the International Myeloma Working Group Guidelines)
Patients who have not received any chemotherapy treatment for multiple myeloma prior to being enrolled in the study
Patients who were receiving simvastatin (dose > 40 mg/day) while receiving current chemotherapy regimen for multiple myeloma
Completion of last anti-myeloma therapy (if any) must occur at least 14 days before conditioning
Multiple myeloma that does not express M-protein or FLC (i.e., non-secretory MM is excluded), and quantitative immunoglobulin levels cannot be used instead.
Relapsed/refractory myeloma
Participants must have histologically confirmed multiple myeloma that is relapsed or refractory
Participants must have a diagnosis of relapsed multiple myeloma according to standard criteria established by the International Myeloma Working Group
Patients may have had 1 or more prior chemotherapy regimens for multiple myeloma but none within the preceding 14 days
Patients who are suffering from symptoms of bone metastases or multiple myeloma bone lesions:
Patients who will undergo their first autologous hematopoietic stem cell transplantation (HSCT) procedure as treatment for multiple myeloma
Autologous transplant recipients with multiple myeloma or lymphoma (both Hodgkin’s and non-Hodgkin’s types) will be eligible to participate in the study; those with other disease types will be excluded
Diagnosis of cancer, not including multiple myeloma or lymphoma/leukemia
Multiple myeloma or plasma cell leukemia with a PR or better to the last treatment regimen, based on the International Myeloma Working Group (IMWG) criteria
Diagnosis of multiple myeloma
Histologies of myeloma or lymphoma
Patients with pathologically diagnosed who have received induction chemotherapy, with or without autologous stem cell transplantation (AuSCT), and who have qualified to receive lenalidomide-based maintenance therapy for their multiple myeloma (MM)
Documented evidence of multiple myeloma (per local assessment):
Nonsecretory multiple myeloma based upon standard M-component criteria (ie, measurable serum/urine M-component) unless the baseline serum free light chain level is elevated
Documented diagnosis of multiple myeloma, currently with complete response (CR) or very good partial response (VGPR) (as defined by International Myeloma Working Group [IMWG] criteria), at least two years after induction therapy or autologous stem cell transplant
Diagnosis of multiple myeloma
Participants must have histologically or cytologically confirmed diagnosis of solid tumor malignancy, lymphoma, or multiple myeloma
High risk, or refractory and relapsed multiple myeloma
Multiple myeloma in CR/very good partial response (VGPR)
Part 1/dose escalation; Histologically or cytologically confirmed diagnosis of Multiple Myeloma in a subject who fulfills all of the following: has undergone stem cell transplant, or is considered transplant ineligible, has been pretreated with at least the 3 following classes of anti-myeloma drugs: alkylators, proteasome inhibitors and immunomodulators, has demonstrated progression on, or within 60 days of completion of the last therapy. Part 2 /MM cohort; Histologically or cytologically confirmed diagnosis of: Multiple Myeloma in a subject who fulfills all of the following: has undergone stem cell transplant, or is considered transplant ineligible, has been pretreated with at least the 3 following classes of anti-myeloma drugs: alkylators, proteasome inhibitors and immunomodulators, has demonstrated progression on, or within 60 days of completion of the last therapy, and has measurable disease with at least one of the following: serum M-protein >=0.5 gram (g)/decilitre (dL) (>=5 g/Litre (L)), urine M-protein >=200 milligram (mg)/24hour (h). Serum free light chain (FLC) assay: Involved FLC level >=5 mg/dL (>=50 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65) and biopsy proven plasmacytoma (should be measured within 28 days of Screening Visit).
Multiple myeloma (MM), requiring treatment, defined by any of the following:
Multiple myeloma meeting the following criteria:
Pathologically-documented diagnosis of multiple myeloma that is relapsed or is refractory as defined by the following:
Multiple myeloma with IgM subtype
Subject has aplastic anemia or multiple myeloma
Patients with multiple co-existing central venous catheters at the time of enrollment will not be enrolled; multiple lumens in a single catheter are acceptable
Diagnosed with multiple myeloma and in complete, partial or very good partial remission at enrollment as per standard International Myeloma Working Group Criteria
Histologically confirmed multiple myeloma (newly diagnosed or relapsed); (Note: multiple myeloma patients with secondary amyloidosis are eligible)
Patients with the clinical diagnosis of multiple myeloma (MM) will be referred to MRI by hematologists/oncologists at New York University Medical Center (NYUMC) who care for these patients
A prior diagnosis of multiple myeloma with documented disease progression
Previous cytotoxic therapies, including cytotoxic investigational agents, for multiple myeloma within defined values prior to start of study treatment
Subject must have a pathologically documented, definitively diagnosed, multiple myeloma relapsed, or refractory progressive disease after at least 2 lines of therapy for multiple myeloma. Prior therapeutic treatment or regimens must include a proteasome inhibitor and lenalidomide.
Multiple myeloma with IgM subtype.
Have history of paraproteinemias or multiple myeloma
NORMAL VOLUNTEERS: Have history of paraproteinemias or multiple myeloma
Has received previous myeloma-specific therapy.
Documentation of r/r MM as defined by the International Myeloma Working Group (IMWG) criteria.
Relapsed multiple myeloma
Received at least 1 prior treatment regimen or line of therapy for multiple myeloma
Immunoglobulin M (IgM) multiple myeloma
Diagnosis of multiple myeloma with documented relapsed or refractory disease according to international Myeloma Working Group (IMWG) criteria, or relapsed/refractory plasma cell leukemia
Previous treatments for multiple myeloma (MM) within 2 weeks of initiation of study treatment
Hematologic malignancies or multiple myeloma.