Pathologically confirmed metastatic or unresectable cholangiocarcinoma or gallbladder carcinoma (GBC), having received at least 1 prior line of systemic therapy, and received no more than 2 prior lines of therapy in the metastatic setting (disease recurrence < 6 months from the last dose of adjuvant therapy in resected patients will be considered the first line of therapy)\r\n* Includes intrahepatic cholangiocarcinoma (IHC), extrahepatic cholangiocarcinoma (EHC), and gallbladder carcinoma (GBC), but not ampulla of vater cancers
Subjects may have had up to 8 cycles of standard first-line platinum-based chemotherapy for mUC (e.g., as per National Comprehensive Cancer Network [NCCN] guidelines); able to commence study treatment within 2 to 6 weeks of receiving last dose of first-line chemotherapy
Documented disease progression after at least 1 line of prior systemic therapy.
Patients must have progressed (in the opinion of the treating investigator) following the most recent line of therapy
Patients must have progressed radiographically following first line platinum-based chemotherapy, no additional lines of therapy are permitted\r\n* NOTE: Prior adjuvant chemotherapy for early stage disease does not count as one line of therapy if 12 months or greater elapsed between completion of adjuvant therapy and initiation of first-line systemic therapy; if less than 12 months elapsed, adjuvant chemotherapy counts as one line of therapy\r\n* Exception for targeted therapy sub-study (Arm T): At least one line of prior chemotherapy or targeted therapy is required, but there is no limit on number of prior treatments
Patients must have either failed to achieve a complete remission, or must have relapsed within 2 years after completing first line bendamustine-containing chemoimmunotherapy (including an anti-CD20 monoclonal antibody), as measured from the last dose of bendamustine; relapsed patients must not have received any intervening chemotherapy; patients must have received at least 3 cycles of bendamustine as first line therapy; (note that no minimum dose of bendamustine is required); patients who additionally received any maintenance anti-CD-20 antibody based therapy or consolidative radioimmunotherapy within 2 years of the last dose of the bendamustine therapy are eligible; involved field or involved site radiation is not considered a line of therapy; patients who previously received anthracycline based therapy are excluded; examples of eligible 1st line treatment regimens (note this list is not all inclusive):\r\n* Bendamustine rituximab x 4 cycles\r\n* Bendamustine bortezomib rituximab x 6 cycles followed by rituximab maintenance\r\n* Bendamustine obinutuzumab x 3 cycles
1 prior line of systemic therapy for multiple myeloma, where a line of therapy for myeloma is defined as 1 or more planned cycles of single agent or combination therapy, as well as a planned series of treatment regimens administered in a sequential manner (e.g. lenalidomide, bortezomib and dexamethasone induction therapy for 4 cycles followed by autologous stem cell transplantation and then lenalidomide maintenance therapy would be considered 1 line of prior therapy); a new line of therapy begins when a planned therapy is modified to include other treatment agents (alone or in combination) as a result of disease progression, disease relapse or treatment-related toxicity (e.g. a patient is progressing in the face of lenalidomide maintenance therapy and has bortezomib and dexamethasone added into their regimen); a new line of therapy also begins when a planned treatment-free interval is interrupted by the need to start treatment due to disease relapse/progression (e.g. a patient with relapsed myeloma achieves a partial response after a planned 8 cycles of cyclophosphamide, bortezomib and dexamethasone, enjoys an 8-month period off therapy but then experiences disease progression requiring re-initiation of therapy)
Patients receiving targeted therapy (non-cytotoxic, non-immunotherapy based systemic therapy) for NSCLC in the first-line setting. Such designations would include but not be limited to treatments targeting EGFR mutant positive or ALK positive NSCLC in the first-line setting.
No more than one prior line of chemotherapy for GCT (other than the 1 cycle of salvage chemotherapy)\r\n* Definition of one line of chemotherapy: One line of therapy can in some cases consist of 2 different cisplatin-based treatment combinations, provided there is no disease progression between these two regimens; for example, a patient could have received 2 cycles of bleomycin, etoposide, and cisplatin (BEP) followed by 2 cycles of cisplatin, ifosfamide, and etoposide (VIP) if the switch from BEP to VIP was made due to pulmonary toxicity rather than disease progression; this would be considered 1 line of prior therapy; in addition, if a patient received 4 cycles of BEP and then underwent post-chemotherapy resection of residual tumor with findings of residual viable non-teratomatous GCT, and subsequently received 2 additional cycles of adjuvant chemotherapy (etoposide, cisplatin [EP] or an alternate regimen such as VIP) in the absence of disease progression, this would also be considered 1 regimen; however, if any change in therapy is prompted by tumor progression including rising tumor markers, this is considered to represent 2 lines of prior treatment\r\n* Prior treatment with carboplatin as adjuvant therapy is allowed, provided patients meet other eligibility criteria (e.g., the patient has also received 3-4 cycles of cisplatin-based chemotherapy)\r\n* Prior treatment with 1-2 cycles of BEP or EP as adjuvant chemotherapy for early stage GCT is allowed, provided the patient also received 3-4 cycles of BEP or EP again at relapse; patients treated with 3-4 cycles of VIP at relapse following 1-2 cycles of BEP/EP are not eligible as this would be considered more than 1 line of prior therapy
SCLC, endometrial carcinoma: one prior chemotherapy-containing line.
For Phase 2 only, have had disease progression or be refractory or intolerant to 1 prior line of therapy (first line therapy) for recurrent or refractory for NSCLC or HCC and have refused currently approved second-line therapy. First line therapy is defined as therapy used to treat advanced disease. This may include multiple chemotherapeutic, targeted or immunotherapeutic agents with or without radiation therapy and/or surgery. Each subsequent line of therapy is preceded by disease progression. A switch of an agent within the same drug class (eg, cisplatinum to carboplatinum) within a regimen in order to manage toxicity does not define the start of a new line of therapy.
For Phase 2 only, more than 1 prior line of therapy for their tumor type.
At least 1 prior line of therapy
Expansion Phase: Initially, only immunotherapy naïve subjects who have progressed on first-line cytotoxic chemotherapy or who have declined first-line treatment with cytotoxic chemotherapy will be enrolled. Subjects with no prior systemic anti cancer therapy (i.e. first line therapy) may be enrolled in a second cohort if approved by the SMC. Subjects previously treated with systemic adjuvant therapy, other than immunotherapy for recurrent advanced NSCLC, are also eligible.
Previously treated with no more than one line of prior systemic therapy for stage IIIb or IV lung cancer\r\n* For patients who have previously treated one line of prior systemic therapy for stage IIIb or IV lung cancer, they must have exhibited evidence of disease progression clinically and/or radiographically on or after that treatment\r\n* Patients who previously received neoadjuvant, concurrent, or adjuvant chemotherapy for localized NSCLC and then recurred within 6 months of completing chemotherapy will be considered as having received one line of prior therapy; patients who relapse > 6 months after completing chemotherapy as part of neoadjuvant/concurrent/adjuvant therapy for localized disease, and thereafter receive additional one line of chemotherapy at the time of metastatic disease will be eligible\r\n* Maintenance therapy does not count as a separate line of therapy
Have progressed during or after completion of first line systemic chemo therapy\r\n* No limit to the number of prior chemotherapy regimens\r\n* Early progression on/after adjuvant chemotherapy counts as first-line therapy
INCLUSION CRITERIA FOR SECOND-LINE THERAPY: Actively on first line therapy for metastatic pancreatic cancer
INCLUSION CRITERIA FOR SECOND-LINE THERAPY: Patients may have had neo-adjuvant and/or chemotherapy that must have been completed > 3 months prior to starting first line therapy
INCLUSION CRITERIA FOR SECOND-LINE THERAPY: Patients may be actively on “maintenance” therapy, such as maintenance capecitabine up to starting first line therapy for metastatic disease
Patients must have received at least one prior line of targeted therapy
Received at least one prior line of therapy for incurable or metastatic NSCLC. Up to one prior line of checkpoint inhibitor therapy is permitted (must have received at least 6 months of treatment).
A line of therapy is defined as a course of therapy that is not interrupted by progressive disease; for example, induction therapy, autologous stem cell transplantation, and maintenance therapy without intervening progressive disease is one line of therapy
Must have relapsed or refractory disease after 2 or more prior lines of therapy; 1 line of therapy is allowed, if it included an autologous stem cell transplant and at least 12 weeks have elapsed from day 0; a line of therapy is defined as a course of therapy that is not interrupted by progressive disease
TREATMENT: Diagnosis of Hodgkin’s or non-Hodgkin’s lymphoma:\r\n* GROUP A: \r\n** With active disease \r\n*** In second or subsequent relapse\r\n*** In first relapse for indolent lymphoma after first line therapy for relapse\r\n*** Or first relapse if immunosuppressive chemotherapy contraindicated\r\n*** Primary refractory disease or if persistent disease after first line therapy of relapse\r\n** Or multiply relapsed patients in remission who are at a high risk of relapse or the lymphoma is a second malignancy e.g. a Richter's transformation of CLL after failing frontline therapy OR\r\n* GROUP B:\r\n** After autologous or syngeneic SCT (as adjuvant therapy)
Patients must have histologically documented metastatic solid tumors which have progressed after one line of therapy, or lymphoma which has progressed after all Food and Drug Administration (FDA)-approved therapy; this trial will enroll a minimum of 5 lymphoma patients
Must not have received more than 4 lines of cytotoxic chemotherapy. A line of therapy is defined as being preceded by disease progression. Discontinuation of a regimen without progression (for example, due to toxicity) or a switch of an agent within the same drug class (for example from cisplatin to carboplatin) will not be considered a new line of therapy. Similarly, maintenance therapy (continuation maintenance or switch maintenance) will not be considered a new line of treatment.
If prior therapy consisted of palliative chemoradiation therapy, it will be considered one line of therapy.
Have received at least 1 prior line of therapy and meets at least one of the following criteria:
Experienced documented objective radiographic or clinical disease progression during first-line therapy or within 4 months after the last dose of first-line therapy with any platinum/fluoropyrimidine doublet with or without anthracycline (epirubicin or doxorubicin) or taxane (docetaxel) for unresectable or metastatic disease
Patients must have histologically documented metastatic solid tumors which have progressed after one line of therapy, or lymphoma which has progressed after all Food and Drug Administration (FDA)-approved therapy
Phase Ib: Subjects who progressed after first-line platinum-based chemotherapy and who are candidates for second-line therapy.
Prior treatment with one additional second line hormone therapy is permitted
More than one prior line of systemic therapy for advanced CRC
Patients must have histologically confirmed unresectable NSCLC for which nivolumab is clinically appropriate. Patients must have had one line of prior therapy and have progressed or have discontinued due to toxicity.
EXPANSION COHORT: Histologically or cytologically confirmed diagnosis of advanced pancreatic adenocarcinoma; \r\n* Maintenance group (n=10): Patients must be stable on front-line therapy (defined as at least 4 months stable disease on nab-paclitaxel + gemcitabine)\r\n* Second-line group (n=10): Patients must have failed or could not tolerate the front-line fluorouracil (5FU)-based therapy for advanced pancreatic cancer
Has received at most 1 line of prior non-gemcitabine chemotherapy for metastatic/unresectable disease\r\n* Prior adjuvant gemcitabine, if completed more than 12 months prior to enrollment is not considered as prior line of therapy\r\n* Radiosensitizing chemotherapy will not be considered a prior line of therapy
All patients must have had at least one appropriate first line systemic therapy and progressed
COHORT B, GROUP 5: MESOTHELIOMA: Patients must have failed a minimum of one previous line of systemic therapy for advanced disease
COHORT B, GROUP 7: GALLBLADDER CANCER OR CHOLANGIOCARCINOMA: Patients must have failed a minimum of one previous line of systemic therapy for advanced disease
All patients must be refractory to approved standard systemic therapy; specifically:\r\n* Metastatic colorectal patients must have received oxaliplatin or irinotecan\r\n* Hepatocellular carcinoma patients must have received sorafenib (Nexavar) since level 1 data support a survival benefit with this agent\r\n* Breast and ovarian cancer patients must be refractory to both first (1st) line and second (2nd) line treatments and must have received at least one second line chemotherapy regimen\r\n* Patients with recurrent glioblastoma that have received standard surgery, radiation therapy, and chemotherapy for their primary tumors and require resection of their tumors for palliative or other clinical indications; these patients will not undergo surgery solely for treatment on this protocol
Demonstrated disease progression during, or after discontinuation, of the most recent line of systemic therapy
Prior therapy with at least one first-line standard of care treatment or second-line treatment of proven effectiveness; patients must have progressive disease after prior treatment; prior first-line or second-line treatments would include the following:\r\n* Patients with metastatic melanoma: receipt of a checkpoint inhibitor as first-line therapy\r\n* Patients with metastatic melanoma with an activating mutation of KIT: receipt of imatinib\r\n* Patients with a BRAF V600 activating mutation: receipt of appropriate targeted therapy\r\n* Patients with metastatic gastrointestinal cancer: receipt of up to two forms of approved first- and/or second-line chemotherapy regimens\r\n* Patients with metastatic genitourinary cancers: receipt of a first- or second-line therapy appropriate for their histologic subtype
Previous first line treatment with at least radiotherapy.
Subjects must have progressed on or after standard first-line systemic chemotherapy
Refractory to approved standard systemic therapy; specifically\r\n* Patients with metastatic colorectal cancer must have received oxaliplatin or irinotecan\r\n* Patients with breast and ovarian cancer must be refractory to both 1st line and 2nd line treatments\r\n* Patients with lung cancer must have received at least one platinum-based chemotherapy regimen and at least one Food and Drug Administration (FDA) approved targeted treatment (when appropriate)\r\n* Patients with glioblastoma must have progression of disease after radiotherapy (including patients that undergo surgery for recurrent disease and are rendered no evidence of disease [NED]); this includes recurrent glioblastoma (GBM) after receiving all standard first-line treatment, including surgery (if feasible due to neurosurgical and neuro-anatomical considerations) and adjuvant radiotherapy +/- chemotherapy
Have a documented advanced (metastatic and/or unresectable) gastroesophageal adenocarcinoma that is incurable and for which prior first-line or later-line standard of care (SOC) treatments have failed. There is no limit to the number of prior treatment regimens. Prior neoadjuvant or adjuvant therapy included in initial treatment may not be considered first- or later-line SOC treatment unless such treatments were completed less than 12 months prior to the current tumor recurrence.
One prior line of chemotherapy and/or targeted agents for metastatic disease are permitted. This chemotherapy can include maintenance therapy, as long as it was given in the front line setting. In addition, prior antiangiogenic therapy (e.g. bevacizumab) is permitted if used as frontline treatment.
In the Phase 2 part, prior olaratumab/doxorubicin combination therapy in 1 prior treatment line is allowed.
Patients must have progressed on at least one prior line of chemotherapy, targeted therapy, palliative radiation and/or biological therapy regimen for their recurrent and/or metastatic HNSCC; however, if patients are likely to be intolerant to standard first-line systemic chemotherapy, the patients are eligible to enroll to this study as the first-line therapy
Patient may be enrolled at any time from last line of therapy
Patients with incurable, advanced or metastatic disease refractory to at least one previous line of therapy
Any line of prior therapy allowed.
At least one prior line of systemic treatment; if the only prior line of treatment was adjuvant or neoadjuvant, patient must have completed treatment within 12 months; there is no limit to number of prior therapies
Have had at least 1 prior line of standard therapy
Disease not amenable to standard treatment (nonresectable or disease present after one or more surgeries and/or sandostatin treatment) or subject has failed existing first line chemotherapy, biologic therapy, targeted agent therapy or radiation therapy
Must have progressed on at least one line of prior therapy for metastatic disease, or be intolerant to that therapy if they have not progressed, and for HER2+ disease should have received prior trastuzumab
Patients must have progressed during or after first-line treatment for metastatic or unresectable disease with either a platinum-based regimen (e.g. carboplatin + etoposide, ifosfamide, and cisplatin [VP16], cisplatin + VP-16, leucovorin calcium, fluorouracil, and oxaliplatin [FOLFOX]) OR temozolomide-based regimen; patients must have failed at least one line of therapy but no maximum number of therapies is exclusionary (i.e. second-line therapy and beyond)
Patients should have received at least one line of approved chemotherapy and/or hormonal therapy
Must have had a relapse or progressive disease (PD) after having received 2 or more prior lines of systemic therapy. Note: A line of therapy is defined as 1 or more cycles of a planned treatment program; this may consist of 1 or more planned cycles of single-agent therapy or combination therapy, as well as a sequence of treatments administered in a planned manner. For example, a planned treatment approach of induction therapy followed by autologous stem cell transplantation (SCT), followed by maintenance is considered 1 line of therapy. Typically each line of therapy is separated by PD.
Prior allogenic bone marrow transplantation in any prior line of therapy or prior autologous SCT in the last prior line of therapy.
All patients must have progressed on at least one line of cytotoxic therapy for metastatic disease
Patients with DLBCL who have received chemotherapy or immunotherapy (except one week of steroids as described above) at any time point in the past for therapy of the DLBCL; patients with low grade B cell lymphomas who have received more than one prior line of chemotherapy or any anthracycline-containing therapy in the past for their low grade B cell lymphoma; localized radiation therapy does not count as a line of therapy
Pancreas patients must have progressed on at least 1 prior line of chemotherapy
Adequate vascular access for leukapheresis procedure (either peripheral line or surgically placed line)
One prior line of therapy is allowed.
Status post first-line therapy with definitive surgery (which provided tissue for pathologic diagnosis) and chemotherapy
Refractory disease is defined as no complete remission to first-line therapy; subjects who are intolerant to first-line therapy are excluded.
Stable disease (SD) as best response after at least 4 cycles of first-line therapy
Relapsed disease defined as complete remission to first-line therapy followed by biopsy-proven relapse ? 12 months of initiating first-line therapy
Subjects must have received adequate first-line therapy including at a minimum:
Prior therapy: eligible subjects must have had at least one line of platinum-based chemotherapy; this may be adjuvant therapy or first line of cytotoxic therapy for metastatic disease; prior hormonal therapy for metastatic/recurrent disease, prior targeted therapy, and prior radiotherapy are allowed; no maximum number of previous lines of chemotherapies; concomitant chemo-radiation is not considered as previous line of systemic chemotherapy
Pathologically confirmed PCNSL or PTL who failed or did not respond to at least 1 line of systemic therapy
Previous first line therapy with at least radiotherapy
Subject has received at least one line of prior therapy
Any line of prior therapy - patients may be chemo-naive or chemo-refractory (any line)
Primary refractory (at least 1 prior line of therapy)
Received more than 1 line of systemic treatment for advanced/metastatic CRC and/or a patient whose first line therapy did not contain oxaliplatin and bevacizumab
At least 1 prior line of chemoimmunotherapy if primary refractory or relapsed within one year; subjects who respond to initial therapy for greater than one year must have had at least 2 prior lines of therapy including one line with chemoimmunotherapy including an anti-CD20 monoclonal antibody
Progression during or after first line chemotherapy or chemoradiotherapy; prior maintenance therapy, targeted therapy, and immunotherapy are allowed; prior use of rovalpituzumab is allowed; immunotherapy or targeted therapy will not be considered as second line therapy
Patients must be appropriate candidates for letrozole therapy in any line of therapy or for fulvestrant for second line of therapy or beyond
Failed at least one line of chemotherapy; neoadjuvant and adjuvant chemotherapy count as a prior line of therapy
Received at least one prior line of therapy including immuno-chemotherapy.
Patients with unmutated (=< 2% homology with germ line) IGHV
Patients must have had front line therapy for their disease
Participants who received more than one line of previous therapy (including HD-ASCT), and have achieved a duration of response (CR or PR) of at least 8 weeks (from the last day of the last cycle) after their last line of therapy
Has primary refractory disease (this is, those whose tumors have progressed at the first restaging during first line therapy)
To be eligible for Cohort 6, patients must have failed one prior line of systemic therapy for advanced/metastatic disease
Phase 2: Subjects must not have received more than 1 prior line of therapy for locally advanced or metastatic NSCLC. First-line treatment must include an EGFR TKI, and subjects must have documented disease progression during or following treatment. Subjects with disease that progressed more than 6 months after completion of neoadjuvant/adjuvant chemotherapy or chemoradiation therapy are eligible if they received an EGFR TKI as first-line treatment for advanced NSCLC.
Refractory or relapsed myeloma, defined as one or more of the following: \r\n* Treated with first-line therapy including at least 2 cycles of lenalidomide, bortezomib or thalidomide, and one or more of the following: \r\n** Less than partial response (PR) to first-line therapy\r\n** Relapse after first (1st) line therapy\r\n* High-risk cytogenetics, defined by deletion (del)(13q) by conventional cytogenetics, or by del(17p), t(4;14), t(14;16), t(14;20) or 1q+ by fluorescence in situ hybridization (FISH)\r\n* Relapse after a prior autologous stem cell transplant (ASCT)\r\n* Plasma cell leukemia\r\n* Soft tissue plasmacytoma
ARM B COHORT 3: Patients must have failed one prior line of systemic therapy for the treatment of advanced non-small cell lung cancer; prior adjuvant therapy with subsequent recurrence within 6 months of completion of therapy will count as one prior line of systemic therapy and such patients will be eligible
ARM B COHORT 3: Patients must not have had more than one prior line of systemic therapy for advanced non-small cell lung cancer (including treatment with a targeted agent); prior adjuvant therapy completed more than 6 months prior to disease recurrence will not count as a prior line of systemic therapy for advanced disease
Patients must have documentation of a defined initial progression free interval (PFI 1) of greater than 6 months following front-line therapy
Patients must previously have received at least one prior line of therapy for their disease
At least 1 prior line of chemotherapy
Previously treated with no more than two lines of prior systemic therapy for advanced stage lung cancer\r\n* Patients who previously received neoadjuvant, concurrent, or adjuvant chemotherapy for localized NSCLC and then recurred within 6 months of completing chemotherapy may be considered as having received one line of prior therapy\r\n* Maintenance therapy does not count as a separate line of therapy
Participants must be within 6 months of initiating TKI treatment, which specifically targets the actionable mutation their tumor harbors (i.e., first-line TKI, or a next-line TKI that targets tumors with acquired resistance to first-line TKI)
Available Viralym-A T cell line.
Progressive disease or intolerable toxicities during or after treatment with first-line chemotherapy and have not received further second-line chemotherapy; patients treated with prior chemo-radiation to the primary pancreatic tumor, for which the chemotherapeutic agent was used as a radio-sensitizing agent, are eligible
Participants must have received at least one line of prior systemic chemotherapy and must have experienced documented radiographic progression or intolerance on this therapy
Follicular lymphoma, previously identified as CD19+\r\n* At least 2 prior chemotherapy or immunochemotherapy regimens (not including single agent monoclonal antibody therapy)\r\n* Patients who progress within 2 years after second or higher line of therapy will be eligible; for instance, patients who have progression of lymphoma < 2 years after second or greater line therapy, but who have responded to their most recent treatment (3rd line or higher) will be eligible; patients may have progression, stable disease or responding disease at the time of enrollment\r\n* Patients with a history of large cell transformation are eligible
Patients must have had, or refused first-line standard chemotherapy for their inoperable malignancies
documented progression on the most recent line of therapy
Patients whose tumors harbor an ALK rearrangement must have demonstrated progression on or intolerance to an FDA-approved first-line TKI; if the first-line TKI was crizotinib, then they also must have demonstrated progression on or intolerance to an FDA-approved second-line TKI; patients who received alectinib or ceritinib as first-line therapy and have demonstrated progression or intolerance will be eligible for this trial
Histologically documented advanced solid tumors that meet protocol-defined cohort specifications, have progressive disease at study entry, and have received at least one line of prior systemic therapy or for which no alternative therapy to prolong survival exists
Patients must have received one prior line of platinum-based systemic anticancer therapy for advanced or metastatic NSCLC. Prior maintenance therapy is allowed and will be considered as the same line of therapy when continued at the end of a treatment regimen.
Patients who never achieved at least minor response (MR) to at least one prior line of therapy
Adequate vascular access for leukapheresis procedure (either peripheral line or surgically-placed line)
Subjects with a central line-related mycobacterial infection; or
Have been previously treated with at least 1 prior line of MM therapy, and must have documented disease progression during or after their most recent therapy according to the IMWG criteria.
Recurrence or refractory to 1 line of systemic chemotherapy.
For Part 2, prior treatment with less than 2 prior line of chemotherapy
Stable on, or responding to 1st line therapy for metastatic disease \r\n* At least 8 and not more than 16 weeks after initiating 1st line therapy for metastatic disease\r\n* Tumor stability/response on 1st line therapy will be determined as per RECIST 1.1
Had at least one prior line of systemic chemotherapy for metastatic disease; adjuvant therapy would not count toward first-line therapy unless patient recurs less than 6 months after completion of that regimen
Patients must have prior chemotherapy for advanced CRC and have previously received both an oxaliplatin and an irinotecan based regimen; patients who are not appropriate for second line therapy because of their KRAS gene mutational status or because they cannot tolerate second line therapy, will be included even after only one prior therapy regimen
Patients must have had, or refused first-line standard chemotherapy for their inoperable malignancies
Failed first-line chemotherapy (including systemic and local-regional therapy)
Any line of treatment (first line versus beyond first line)
The dose of nilotinib for patients receiving the drug in the second line setting due to failure of a first line TKI is generally 400 mg PO BID; in addition, if a patient is unable to tolerate second line nilotinib at 400 mg PO BID their dose may be decreased to 300 mg PO BID; in both instances they will be eligible for phase I
The target population of this study are patients who have a suboptimal response to steroids as their first line of treatment for acute GVHD (ie steroid refractory); this protocol is designed to provide second line therapy, and is not for patients (pts) in whom additional, alternate immunosuppressive agents have already been added
First or second line chemotherapy treatment for metastatic disease
Patients must have received and completed first line therapy
Be receiving first-line therapy for metastatic disease
All patients must have also had a treatment-free interval without clinical evidence of progressive disease of at least 6 months from completion of front-line chemotherapy (both platinum and taxane); front-line therapy may have included a biologic agent (i.e. bevacizumab)
Previous first line therapy with at least radiotherapy and temozolomide.
For Parts 3 and 4, subjects must have progressed following at least 1 line of prior therapy, and the treatment with the select SOC agent is relevant for the specific disease cohort.
For participants who are ineligible for auto-SCT, has received at least ?2 lines of prior therapy and has failed to respond to or relapsed after their last line of treatment. For participants who received consolidative local radiotherapy after systemic therapy, local radiotherapy will not be considered as a separate line of treatment.
Must have failed last line of treatment (refractory to last line of treatment).
Must have undergone prior treatment with ?2 treatment lines of anti-myeloma therapy and must have failed last line of treatment (refractory to last line of treatment)
Hydroxyurea will not be considered a prior line of treatment.
Hydroxyurea will not be considered a prior line of treatment.
No more than one prior line of systemic treatment for glioblastoma. Concurrent and adjuvant TMZ-based chemotherapy, including the combination of TMZ with an investigational agent, is considered one line of therapy.
Have received a second line chemotherapy after progressing on or not tolerating treatment with FOLFIRINOX as a first line. Prior adjuvant/neoadjuvant gemcitabine or gemcitabine-based radiation will not be counted as first line therapy.
Must have failed last line of treatment (refractory to last line of treatment).
Occurrence or progression of BM while receiving first line therapy (either erlotinib, afatinib, or gefitinib) for at least 14 days. Patients may have received osimertinib (or other agents inhibiting the T790M EGFR mutation) as second line therapy. If BM progression occurs after osimertinib, patient will be eligible.
Subjects must have received at least 1 line of chemotherapy for metastatic MCC and must have progressed after the most recent line of chemotherapy
received at least one, but no more than three previous systemic regimens for the treatment of DLBCL and one therapy line must have included a CD20-targeted therapy
Patients must have progressed on or within 60 days after end of previous therapy before to study entry, i.e., refractory to the last line of treatment.
Has received a front line platinum-based regimen (administered via either intravenous or intraperitoneal route) per local standard of care or treatment guideline following the primary or interval debulking surgery with documented disease recurrence (note: Maintenance treatment following the front line treatment is permitted and counted together as part of the front line treatment)
Disease not amenable to standard treatment (nonresectable or disease present after one or more surgeries and/or sandostatin treatment) or subject has failed existing first line chemotherapy, biologic therapy, targeted agent therapy or radiation therapy
Achievement of SD or PR after a minimum of 12 weeks of pre-study first- or second-line standard chemotherapy
Up to 4 prior lines of systemic therapy (biologic or chemotherapy) are allowed; maintenance therapy after 4-6 cycles of front-line chemotherapy is still considered 1 line of therapy and is not considered 2 separate therapies
In Part A, prior treatment with at least one line of a single agent EGFR TKI and at least 1 line of chemotherapy.
Each subsequent line of therapy must be preceded by disease progression. A switch of an agent within a regimen in order to manage toxicity does not define the start of a new line of therapy
Prior treatment with nintedanib or any other prior line of therapy
For subjects who have discontinued anti-androgen therapy, PSA rise as defined above must be documented:\r\n* Within two weeks after discontinuation if used following surgical or medical castration (second line therapy)\r\n* After four weeks discontinuation if used as first line therapy
Prior anti-androgen therapy: first line of therapy (started simultaneously with LHRH) initiated at least eight weeks prior to screening; second line, anytime before start of study treatment
Any disease-directed radiotherapy (except prophylactic cranial irradiation or pre-planned radiotherapy for CNS metastases present prior to start of first-line therapy and non-progressing) after last dose of first-line chemotherapy.
The patient must have received no more than 1 prior line of therapy for extensive disease.
Progression after at least first-line systemic therapy for metastatic disease
Patients must have disease progressing after treatment with at least one line of therapy including mitotane and/or chemotherapy; Note: Patients who are deemed ineligible to receive first line treatment with mitotane and/or chemotherapy or who decline first line treatment may be eligible for this study after discussion with the principal investigator (PI)
Persistent, recurrent or progressive disease following at least one prior line of systemic therapy and there is no available therapy likely to improve survival
Patients must have failed at least one line of chemotherapy for metastatic disease.
Progression during or after prior first- or second-line chemotherapy and eligible to receive topotecan therapy
Failed first-line chemotherapy
Documented response of at least partial response (PR) to 1 line of prior therapy
ELIGIBILITY FOR TREATMENT ON ARM 1: Patients must have received at least one line of therapy for NSCLC or mesothelioma or previously documented to have declined therapy
Patients who have received second-line antihormonal therapy, including ketoconazole, aminoglutethimide, or high-dose estrogen within 30 days of study entry.
Previous first line therapy with at least radiotherapy and temozolomide
Disease status: all the patients need to have scan or biopsy proven active disease at the time of clinical trial\r\n* Multiple myeloma: patient must have failed at least one line of therapy\r\n* Chronic lymphocytic leukemia (CLL): status post (S/P) at least one line of therapy\r\n* Hodgkin’s lymphoma: S/P at least two lines of therapy\r\n* Follicular lymphoma: S/P at least one line of therapy\r\n* Mantle cell lymphoma: S/P at least one line of therapy\r\n* Diffuse large B cell lymphoma: S/P at least two lines of therapy
At least one prior line of platin-based chemotherapy (unless refused or not tolerated)
Patients must have had at least 2 prior line of therapy
Patient may be enrolled at any time from last line of therapy
Patients must have received first line chemotherapy, from 4-6 cycles, and achieved stable disease or a partial response
Multiple myeloma (MM) in first relapse or refractory to first line therapy; the previous line of therapy should include either an immunomodulatory agent or a proteasome inhibitor\r\n* Refractory disease is defined as =< 25% response or progression during therapy or within 60 days after completion\r\n* The number of prior lines of anti-myeloma therapy will be determined as follows:\r\n** Induction chemotherapy for peripheral-blood stem cell harvest followed by planned mobilization and subsequent high-dose chemotherapy with autologous stem cell transplant (ASCT) is considered one therapy regardless of the induction regimen\r\n** Planned maintenance therapy after stem cell transplantation or other induction therapy is not considered a separate line of therapy, as long as there is no evidence of progression in the time between the induction or transplantation and the initiation of maintenance therapy\r\n** Two ASCTs within 6 months of each other is considered as one line unless different agents were used in the high-dose therapy-conditioning regimens\r\n** If the same regimen is repeated after a 6-month interval, they are considered to be two separate therapeutic lines\r\n** If cyclophosphamide is used for reasons other than planned stem cell mobilization, its use is considered to be a separate line of therapy\r\n** Dose modification of steroid and altering choices of steroid (i.e. from dexamethasone to prednisone) due to side effects, is not considered a line of therapy, as long as there is no evidence of progression\r\n** If a regimen was stopped for more than 2 months, its re-initiation is counted as another line of therapy
At least one prior line of systemic therapy including platinum and pemetrexed
Failure of 1st line anti-cancer therapy due to radiological documentation of disease progression in advanced disease or subsequent relapse of disease following 1st line therapy
Failed standard front-line therapy
Solid malignancy that is refractory to at least one prior line of treatment, or for which no standard therapy exists, is required; one prior line of treatment with irinotecan is allowed
For 1st Line expansion cohort ONLY, confirmation that the tumour is EGFRm+ve and have had no prior therapy for their advanced disease (for 1st line patients biopsy will be at time of diagnosis of advanced disease).
Failure of 1st line anti-cancer therapy due to radiological documentation of disease progression in advanced disease or subsequent relapse of disease following 1st line therapy
Received at least 1 prior line of therapy for MM (Phase 1)
Participants who relapsed from at least 1 previous treatment AND additionally were refractory to at least 1 previous treatment. For the purposes of this study, refractory disease was defined as disease progression on treatment or progression within 60 days after the last dose of a given therapy. A line of therapy was defined as 1 or more cycles of a planned treatment program. This may have consisted of 1 or more planned cycles of single-agent therapy or combination therapy, as well as a sequence of treatments administered in a planned manner. For example, a planned treatment approach of induction therapy followed by autologous stem cell transplantation, followed by maintenance was considered 1 line of therapy. Autologous and allogenic transplants were permitted.
High-risk disease as defined by one of the following: \r\n* First relapse after CR within 12 months of initiation of front-line therapy \r\n* Less than CR to front-line therapy \r\n* Second-line Age-Adjusted International Prognostic Index (sAAIPI) of 2 or higher at the time of relapse
Imaging studies documenting the response to first-line therapy must be available for evaluation by the investigator.
Have received more than 1 line of systemic treatment in Parts A, B and D
Documented progression from most recent line of therapy
* Primary tumor progression on first-line chemotherapy
Indication C - SS: Subjects previously treated with at least one prior line of approved therapy, including first-line anthracycline containing regimen.
Progression on or following, or intolerant of, at least one prior line of standard systemic therapy for advanced or metastatic gastric or pancreatic cancers.
Prior treatment\r\n* Currently receiving first-line treatment with pemetrexed + platinum; patients are to be registered to Cancer and Leukemia Group B (CALGB) 30901 no later than the last day of cycle 4 of first line therapy\r\n* Prior intracavitary cytotoxic or sclerosing therapy (including bleomycin) are acceptable; prior intrapleural cytotoxic chemotherapy will not be considered systemic chemotherapy\r\n* Prior surgical treatment is allowed\r\n* Prior radiation therapy is allowed
Subjects must have a pathologic diagnosis of advanced or recurrent endometrial adenocarcinoma and must have failed at least 1 prior line of standard chemotherapy
Any available standard line of therapy known to be life-prolonging or life-saving
Must have been treated with one of the following in first and/or second line:
Systemic treatment for B-cell CLL in the interval between completing the last cycle of second-line induction therapy and randomization.
Planned first-line chemotherapy contains a proteasome-inhibiting agent administered weekly
Received more than one line of chemotherapy
Must have received at least one (1) line of prior systemic therapy that may NOT have included VELCADE (bortezomib)
Patients whose tumors have progressed on first-line treatment
Participants who have received > 1 prior line of chemotherapy in the advanced or metastatic setting. (Immunotherapy will not be considered a line of chemotherapy.)
Participants who, after the front-line, platinum-based, non-docetaxel containing chemotherapy, have been treated with 1 line of nivolumab or other immune-checkpoint inhibitors but progressed on or after the therapy.
Must have received at least 3 cycles of first-line chemotherapy.
More than one prior line of chemotherapy (i.e., 2nd or 3rd line chemotherapy) for advanced and/or metastatic (stage III B or IV NSCLC) or recurrent disease.
Second-line or higher therapy for any patients with NSCLC with performance status (PS) 0-2
Participants may have received any number of prior lines of chemotherapy (other than erlotinib or other EGFR-targeted therapy) for incurable non-small cell lung cancer; (first line platinum-doublet based chemotherapy plus switch maintenance chemotherapy counts as one line of therapy; prior adjuvant chemotherapy for early stage disease does not count as one line of therapy if 12 months or greater elapsed between completion of adjuvant therapy and initiation of first-line systemic therapy; if less than 12 months elapsed, adjuvant chemotherapy counts as one line of therapy)\r\n* PARTICIPANTS WITH NO PRIOR THERAPY FOR INCURABLE LUNG CANCER: trial eligibility will be restricted to those participants whose tumors harbor known EGFR activating mutations\r\n* PARTICIPANTS WITH PRIOR LINES OF THERAPY: all other participants (those whose tumors harbor wild-type EGFR or unknown EGFR status, or those with EGFR mutations not previously treated with erlotinib/EGFR-targeted therapy)\r\n* At least 4 weeks must have elapsed since prior chemotherapy or biological therapy, 6 weeks if the regimen included carmustine (BCNU) or mitomycin C; prior radiation therapy to the thoracic cavity, abdomen, or pelvis must be completed at least 3 months prior to registration; radiotherapy to any other site (including bone or brain metastases) must be completed at least 28 days prior to registration
SCREENING: Patients must have received or refused first line standard systemic therapy for their metastases
Patient has received more than one line of chemotherapy for advanced disease.
Patients must have completed at least 1 prior line of systemic therapy; patients who have declined first line therapy or for whom first-line therapy would be clinically inappropriate, will be considered eligible for the trial
Patient has received any second line therapy to treat aGVHD prior to screening.
Must have received at least 1 prior line of AML therapy given at standard doses and must have progressed after their most recent therapy. Prior therapy must have included: a hypomethylating agent with at least 2 cycles.
Progressed following at least 1 line of prior therapy and there is no further approved therapy available that has been demonstrated to prolong survival (including subjects who are intolerant to the approved therapy)
second-line or greater salvage systemic therapy, or
Available Viralym-C T cell line
Patients must have already received or refused 1st-line treatment
More than one prior line of therapy for advanced gastric cancer
The cycles of chemotherapy must be consecutive (i.e. one followed by the other) but do not have to be the first and second cycle of a line of treatment.
Stable brain metastasis (defined as asymptomatic and off steroids ?3 months) are permitted in subjects entering LPT112515 on second-line treatment (completed 12-24 weeks of second-line treatment with trastuzumab plus chemotherapy)
Patients must have received one prior approved therapy for metastatic disease and have not curable options, with the exception of HER2+ breast or gastric patients for whom this can be the first line of treatment (no prior therapy)
Relapsed or refractory disease after at least one line of prior therapy. Subjects must have previously received appropriate line(s) of standard of care (SOC) treatment.
2nd line, 3rd line or greater
Patients with Hodgkin’s lymphoma with one or more of the following: \r\n* Less than complete response to first-line chemotherapy\r\n* Relapse within 12 months of completion of first-line chemotherapy\r\n* Relapse within a prior irradiation field\r\n* Less than complete metabolic response to second-line chemotherapy\r\n* Second relapse or beyond\r\n* Extranodal disease at the time of relapse\r\n* Presence of B symptoms at the time of persistent disease upon completion of first-line chemotherapy, relapse or progressive disease\r\n* Bulky disease (defined as any lesion greater than 5 cm) at the time of persistent disease upon completion of first-line chemotherapy, relapse or progressive disease
Patients must have failed one prior line of CT-based therapy for unresectable disease
No primary induction failure, defined as failure to achieve CR with first-line chemotherapy or chemoradiation, disease progression during first-line chemotherapy or chemoradiation, or progression or biopsy-proven disease persistence within 8 weeks of first-line therapy completion
Patients eligible for second-line therapy after failing first-line therapy with the regimen FOLFIRINOX.
Failure of rituximab for first-line treatment of PTLD. Note: Subjects with CD20 negative disease are eligible to enroll without prior anti-CD20 therapy after failure of first-line treatment (reduction of immunosuppression is not considered first-line therapy) and discussion with the sponsor's medical monitor.
Patients must have documented at least partial response (PR) to at least 1 line of prior therapy. PR documentation can be based on Investigator assessment.
HCC patients only:\r\n* First line (i.e., no prior systemic therapy) or second-line (with prior first-line sorafenib therapy only) advanced HCC \r\n* Child Pugh class A or B7 liver disease \r\n* Prior chemoembolization, radioembolization, radiofrequency ablation (RFA), or other local ablative therapies are permissible if >= 6 weeks from procedure with evidence of progression or new metastatic disease, if applicable (Phase I)
Any progression during treatment if the len/dex combination was the subject's most recent line of therapy
Patients must have received at least one prior line of therapy and their disease has relapsed..
Must have had one prior line of systemic therapy for AL; Note: patients who do not achieve at least a PR to frontline therapy in 3 months may be eligible after discussion with study chair
Patients must have received first line standard systemic therapy for their metastases (if applicable)
First-line cytotoxic chemotherapy started within four-weeks of enrollment (patients can have reviewed prior = adjuvant therapy if completed >= 6 months prior to start of first line chemotherapy for metastatic disease)
Patients receiving 3rd-line palliative chemotherapy
Patients with cGvHD who have been exposed to one or more line of therapy, are eligible, providing they are refractory to, or dependent on, glucocorticoids (usually prednisone [PDN]); (in fact, it is anticipated that the majority of patients will be resistant to multiple lines of therapy); in the case in which the glucocorticoid dose-regimens cannot be confirmed accurately the use of one additional line of therapy will substitute
There must be no prior second-line or third line therapies for aGVHD (with exception of mycophenolate mofetil [MMF]) or second or third line therapies for cGVHD (other than extracorporeal photopheresis, rituximab or MMF); second and third line therapies for aGVHD and cGVHD are as defined by the British Committee on Standards in Hematology and reproduced in the GVHD Policy of the Blood and Marrow Transplant program (version 1-13); all prior therapies other than corticosteroids, tacrolimus, sirolimus or cyclosporine must be completed and discontinued; patients with breakpoint cluster region (bcr)-ABL proto-oncogene 1 (abl) associated malignancies may be on a tyrosine kinase inhibitor as malignant disease therapy or prophylaxis
Newly diagnoses or needing a new line of therapy and have not yet made a treatment decision
With income at or below 250% of the poverty line
Presence of an external central line
Have a central line in place prior to IV study therapy
Patients who are unable to have placement of intravenous line access
Well differentiated, low, intermediate, or high-grade, pancreatic NET with documented disease progression within 6 months prior to start of study treatment and evidence of radiographic disease progression based on scans performed not more than 15 months apart. Patients may have received 1 or more prior lines of anticancer therapy, such as somatostatin analogues, targeted agents, or liverdirected intra-arterial therapy, and up to 1 prior line of systemic cytotoxic chemotherapy, but are NOT eligible if they have received more than 1 prior line of systemic cytotoxic chemotherapy or if they have received prior peptide receptor radionuclide therapy (PRRT)
Patient is about to start a new line of ET for their metastatic disease
Subject must have metastatic or recurrent disease and have failed first-line systemic treatment, and if indicated, failed approved second-line therapy, and for whom no standard therapy options are anticipated to result in a durable remission