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Study terminated prematurely due to funding/support being withdrawn by grantor
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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
| Celgene | INDUSTRY |
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For the phase I component of the trial a classic 3 + 3 dose escalation design will be utilized, with a fixed dose of pembrolizumab and an escalating dose of the lenalidomide. The patient population will all have histologically confirmed advanced solid tumor malignancy. The primary endpoint for the phase I component of this protocol will be determining the maximum tolerated dose (MTD) of lenalidomide in combination with pembrolizumab.
The phase II component of this trial will utilize a two stage design, initially enrolling 13 patients, followed by 13 more patients if the early stopping criteria are not met. The target population will include patients with histologically confirmed diagnoses of non-small cell lung carcinoma, regardless of histologic subtype; who have completed one line of standard therapy. The primary endpoint for the phase II component of this protocol will be determining efficacy as measured by progression free survival (PFS)
Phase I The study will plan to enroll 3 patients in an initial cohort, to receive the dose level 1 of lenalidomide (10 mg PO) on days 1-14 of a 21-day cycle, and pembrolizumab (200 mg IV) on day 1. Patients will be evaluated for toxicities after initiation of treatment. If there are no DLTs for the initial 3 patients after one cycle, the next dosing cohort will open, with another 3 patients. Similarly, if the second cohort of patients receives the dose level 2 of lenalidomide (15 mg) for one cycle without DLT, then the third and final cohort will open. When the third cohort testing the dose level 3 of lenalidomide (20 mg) has completed one cycle, the phase I component of the trial will be completed. Standard phase I, 3 + 3 design rules will be utilized as follows: if 1 out of 3 patients experiences a DLT at certain dose level, then 3 more patients will be enrolled at the same level. If 2 out of 6 patients experience DLT at a certain dose level, 3 additional patients are added at the next lower level. Dose reduction is continued until at most 1 of 6 patients experiences DLT. The highest level with at most 1 of 6 patients DLT will be declared MTD. If no dose level achieves this criterion the trial will be discontinued for excess toxicity.
Phase II A pre-treatment (archival) and fresh tumor sample will be needed for participation in trial. PD-L1 expression levels in both samples will be determined to assess the role of chemotherapy on expression level and pattern of this biomarker. Baseline blood samples will be collected for immunologic correlates prior to treatment on Day 1 of Cycle 1 and post treatment at 2, 4, 24 hours. Samples will also be collected prior to treatment on Day 1 of Cycle 2, and at time of progression. Baseline CT scan of the chest and abdomens will be obtained within 30 days prior to the initiation of cycle 1. CT scan with contrast or MRI with contrast of the brain will also be obtained within 30 days prior to the initiation of cycle 1. Time to progression will be measured with disease imaging following every 2 cycles of therapy with a three-day window (+ or -). Patients will continue treatment until disease progression or unacceptable toxicity or two years of therapy. Overall survival will be assessed every 3 months during long term follow up
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pembrolizumab, Lenalidomide | Experimental | Phase I The treatment will be given on a 21-day cycle, with a dose of pembrolizumab given on day1(IV) and doses of lenalidomide given on day 1-14 (orally). The dose of pembrolizumab will be fixed at 200 mg. The dose of lenalidomide will depend upon the patient cohort. Cohort 1 will receive 10mg, Cohort II will receive 15mg and cohort 3 will receive 20mg of lenalidomide. Phase II The treatment will be given on a 21-day cycle, with a dose of pembrolizumab given on day1(IV) and doses of lenalidomide given on day 1-14 (orally). The dose of pembrolizumab will be fixed at 200 mg. Maximum Tolerated Dose (MTD) of lenalidomide as determined by the Phase I study will be given in Phase II study. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lenalidomide | Drug | Lenalidomide is a thalidomide analogue with immunomodulatory, anti-angiogenic, and antineoplastic effects. It is administered as a pill taken orally. It has completed phase III study evaluation and has FDA indications for use in certain patients with multiple myeloma, myelodysplastic syndrome, and mantle cell lymphoma. |
| Measure | Description | Time Frame |
|---|---|---|
| To Determine the Maximum Tolerated Dose (MTD) of Lenalidomide in Combination With a Fixed Dose of Pembrolizumab in Subjects With Relapsed and/or Refractory Solid Tumors. | Maximum tolerated dose of Lenalidomide | Day 22 of cycle 1 |
| To Determine Efficacy as Measured by Progression Free Survival (PFS) in Non-small Cell Lung Cancer Patients | PFS | up to 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Assess Antitumor Activity of the Combination as Measured by Objective Response Rate (ORR) | ORR | upto 2 years |
| Assessment of PD-L1 Expression by Immunohistochemistry | PD-1 expression will be used to correlate with the treatment response |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fox Chase Cancer Center | Philadelphia | Pennsylvania | 19111 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Pembrolizumab, Lenalidomide | Phase I The treatment will be given on a 21-day cycle, with a dose of pembrolizumab given on day1(IV) and doses of lenalidomide given on day 1-14 (orally). The dose of pembrolizumab will be fixed at 200 mg. The dose of lenalidomide will depend upon the patient cohort. Cohort 1 will receive 10mg, Cohort II will receive 15mg and cohort 3 will receive 20mg of lenalidomide. Phase II The treatment will be given on a 21-day cycle, with a dose of pembrolizumab given on day1(IV) and doses of lenalidomide given on day 1-14 (orally). The dose of pembrolizumab will be fixed at 200 mg. Maximum Tolerated Dose (MTD) of lenalidomide as determined by the Phase I study will be given in Phase II study. Lenalidomide: Lenalidomide is a thalidomide analogue with immunomodulatory, anti-angiogenic, and antineoplastic effects. It is administered as a pill taken orally. It has completed phase III study evaluation and has FDA indications for use in certain patients with multiple myeloma, myelodysplastic syndrome, and mantle cell lymphoma. Pembrolizumab: Pembrolizumab is a humanized IgG4 monoclonal antibody which targets the PD-1 receptor, thus inhibiting the interaction between PD-1 and its ligands, PD-L1 and PD-L2 respectively. It is administered as an IV infusion. This drug has several studies in patients with solid tumors and currently has an FDA indication for use in patients with melanoma and non-small cell lung cancer. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 9, 2016 |
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|
|
| Pembrolizumab | Drug | Pembrolizumab is a humanized IgG4 monoclonal antibody which targets the PD-1 receptor, thus inhibiting the interaction between PD-1 and its ligands, PD-L1 and PD-L2 respectively. It is administered as an IV infusion. This drug has several studies in patients with solid tumors and currently has an FDA indication for use in patients with melanoma and non-small cell lung cancer. |
|
|
| upto 2 years |
| Proportions of Blood Immune Cells by Flow Cytometry | Amount of CD45, CD3, CD4, CD8 (T cells), CD19 (B cells), CD14, CD16 (monocytes), CD56 (NK cells), CD11c, HLA-DR, CD303, CD66b (myeloid - DCs and granulocytes). | upto 2 years |
| Assesment of Cytokine Profiles Using Luminex | Th1/Tc1 responses ( IFN-g, TNF, IL-2), Th2/Tc1 responses (IL-4, IL-5, IL-10), pro-inflammatory innate responses (IFN-α, IL-1β, IL-6, IL-17), homeostatic lymphocyte expansion (IL-7, IL-15), and chemotaxis of immune cells (IP-10, MCP-1, MIP-1α, MIP-1β, RANTES) will be measured | upto 2 years |
| Determine Specific NK Cell Responses by NK Degranulation Assay by Flow Cytometry | CD107A expression after 2 hour co-culture with the EBV-transformed B cell line, 721.221, without and with rituximab (ADCC conditions). | upto 2 years |
| Assessment of Activation Markers on Immune Cells by Flow Cytometry | Activation markers will include CD69, CD25, HLA-DR, IL-15Ra, perforin, Ki67, NKp44, CD57 | upto 2 years |
| Determine Immune Composition of Tumors Using PanCancer Immune Profiling Panel by Nanostring Technology | Expression of genes involved in immune responses | upto 2 years |
| From Patients That Were Previously Treated With an Anti-PD1 Antibody, we Will Determine Resistance Overcome Due to the Treatment With Combination Assessed by Overall Response Rate. | number of patients that overcome the resistance of previous anti-pD-1 therapy | upto 2 years |
| Determine Specific T Cell Responses by Determining Differentiation Status of T Cells by Flow Cytometry | Differentiation status of CD4 and CD8 T cells (naïve/effector memory/central memory/regulatory/delta-gamma TCR) as defined by: CD62L, CD45RA, CD127, CD25. | upto 2 years |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Pembrolizumab, Lenalidomide | Phase I The treatment will be given on a 21-day cycle, with a dose of pembrolizumab given on day1(IV) and doses of lenalidomide given on day 1-14 (orally). The dose of pembrolizumab will be fixed at 200 mg. The dose of lenalidomide will depend upon the patient cohort. Cohort 1 will receive 10mg, Cohort II will receive 15mg and cohort 3 will receive 20mg of lenalidomide. Phase II The treatment will be given on a 21-day cycle, with a dose of pembrolizumab given on day1(IV) and doses of lenalidomide given on day 1-14 (orally). The dose of pembrolizumab will be fixed at 200 mg. Maximum Tolerated Dose (MTD) of lenalidomide as determined by the Phase I study will be given in Phase II study. Lenalidomide: Lenalidomide is a thalidomide analogue with immunomodulatory, anti-angiogenic, and antineoplastic effects. It is administered as a pill taken orally. It has completed phase III study evaluation and has FDA indications for use in certain patients with multiple myeloma, myelodysplastic syndrome, and mantle cell lymphoma. Pembrolizumab: Pembrolizumab is a humanized IgG4 monoclonal antibody which targets the PD-1 receptor, thus inhibiting the interaction between PD-1 and its ligands, PD-L1 and PD-L2 respectively. It is administered as an IV infusion. This drug has several studies in patients with solid tumors and currently has an FDA indication for use in patients with melanoma and non-small cell lung cancer. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
| |||||||||||||||||||||||
| Region of Enrollment | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | To Determine the Maximum Tolerated Dose (MTD) of Lenalidomide in Combination With a Fixed Dose of Pembrolizumab in Subjects With Relapsed and/or Refractory Solid Tumors. | Maximum tolerated dose of Lenalidomide | Study terminated prematurely due to funding/support being withdrawn by grantor. No analyses occurred | Posted | Day 22 of cycle 1 |
|
| |||||||||||||||||||
| Primary | To Determine Efficacy as Measured by Progression Free Survival (PFS) in Non-small Cell Lung Cancer Patients | PFS | Study terminated prematurely due to funding/support being withdrawn by grantor. No analyses occurred | Posted | up to 3 years |
| ||||||||||||||||||||
| Secondary | Assess Antitumor Activity of the Combination as Measured by Objective Response Rate (ORR) | ORR | Study terminated prematurely due to funding/support being withdrawn by grantor. No analyses occurred | Posted | upto 2 years |
| ||||||||||||||||||||
| Secondary | Assessment of PD-L1 Expression by Immunohistochemistry | PD-1 expression will be used to correlate with the treatment response | Study terminated prematurely due to funding/support being withdrawn by grantor. No analyses occurred | Posted | upto 2 years |
| ||||||||||||||||||||
| Secondary | Proportions of Blood Immune Cells by Flow Cytometry | Amount of CD45, CD3, CD4, CD8 (T cells), CD19 (B cells), CD14, CD16 (monocytes), CD56 (NK cells), CD11c, HLA-DR, CD303, CD66b (myeloid - DCs and granulocytes). | Study terminated prematurely due to funding/support being withdrawn by grantor. No analyses occurred | Posted | upto 2 years |
| ||||||||||||||||||||
| Secondary | Assesment of Cytokine Profiles Using Luminex | Th1/Tc1 responses ( IFN-g, TNF, IL-2), Th2/Tc1 responses (IL-4, IL-5, IL-10), pro-inflammatory innate responses (IFN-α, IL-1β, IL-6, IL-17), homeostatic lymphocyte expansion (IL-7, IL-15), and chemotaxis of immune cells (IP-10, MCP-1, MIP-1α, MIP-1β, RANTES) will be measured | Study terminated prematurely due to funding/support being withdrawn by grantor. No analyses occurred | Posted | upto 2 years |
| ||||||||||||||||||||
| Secondary | Determine Specific NK Cell Responses by NK Degranulation Assay by Flow Cytometry | CD107A expression after 2 hour co-culture with the EBV-transformed B cell line, 721.221, without and with rituximab (ADCC conditions). | Study terminated prematurely due to funding/support being withdrawn by grantor. No analyses occurred | Posted | upto 2 years |
| ||||||||||||||||||||
| Secondary | Assessment of Activation Markers on Immune Cells by Flow Cytometry | Activation markers will include CD69, CD25, HLA-DR, IL-15Ra, perforin, Ki67, NKp44, CD57 | Study terminated prematurely due to funding/support being withdrawn by grantor. No analyses occurred | Posted | upto 2 years |
| ||||||||||||||||||||
| Secondary | Determine Immune Composition of Tumors Using PanCancer Immune Profiling Panel by Nanostring Technology | Expression of genes involved in immune responses | Study terminated prematurely due to funding/support being withdrawn by grantor. No analyses occurred | Posted | upto 2 years |
| ||||||||||||||||||||
| Secondary | From Patients That Were Previously Treated With an Anti-PD1 Antibody, we Will Determine Resistance Overcome Due to the Treatment With Combination Assessed by Overall Response Rate. | number of patients that overcome the resistance of previous anti-pD-1 therapy | Study terminated prematurely due to funding/support being withdrawn by grantor. No analyses occurred | Posted | upto 2 years |
| ||||||||||||||||||||
| Secondary | Determine Specific T Cell Responses by Determining Differentiation Status of T Cells by Flow Cytometry | Differentiation status of CD4 and CD8 T cells (naïve/effector memory/central memory/regulatory/delta-gamma TCR) as defined by: CD62L, CD45RA, CD127, CD25. | Study terminated prematurely due to funding/support being withdrawn by grantor. No analyses occurred | Posted | upto 2 years |
|
4 months
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Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Pembrolizumab, Lenalidomide | Phase I The treatment will be given on a 21-day cycle, with a dose of pembrolizumab given on day1(IV) and doses of lenalidomide given on day 1-14 (orally). The dose of pembrolizumab will be fixed at 200 mg. The dose of lenalidomide will depend upon the patient cohort. Cohort 1 will receive 10mg, Cohort II will receive 15mg and cohort 3 will receive 20mg of lenalidomide. Phase II The treatment will be given on a 21-day cycle, with a dose of pembrolizumab given on day1(IV) and doses of lenalidomide given on day 1-14 (orally). The dose of pembrolizumab will be fixed at 200 mg. Maximum Tolerated Dose (MTD) of lenalidomide as determined by the Phase I study will be given in Phase II study. Lenalidomide: Lenalidomide is a thalidomide analogue with immunomodulatory, anti-angiogenic, and antineoplastic effects. It is administered as a pill taken orally. It has completed phase III study evaluation and has FDA indications for use in certain patients with multiple myeloma, myelodysplastic syndrome, and mantle cell lymphoma. Pembrolizumab: Pembrolizumab is a humanized IgG4 monoclonal antibody which targets the PD-1 receptor, thus inhibiting the interaction between PD-1 and its ligands, PD-L1 and PD-L2 respectively. It is administered as an IV infusion. This drug has several studies in patients with solid tumors and currently has an FDA indication for use in patients with melanoma and non-small cell lung cancer. | 2 | 3 | 0 | 3 | 3 | 3 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Constipation | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Abdominal distension | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Fecal incontinence | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Anorexia | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| Hypoalkemia | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| Hyponatremia | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| Cough | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Postnasal drip | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Sore throat | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Pruritis | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
| ||
| Hypothyroidism | Endocrine disorders | Non-systematic Assessment |
| ||
| Photophobia | Eye disorders | Non-systematic Assessment |
| ||
| Watering eyes | Eye disorders | Non-systematic Assessment |
| ||
| Chills | General disorders | Non-systematic Assessment |
| ||
| Edema limbs | General disorders | Non-systematic Assessment |
| ||
| Fatigue | General disorders | Non-systematic Assessment |
| ||
| Weight loss | Investigations | Non-systematic Assessment |
| ||
| Dizziness | Nervous system disorders | Non-systematic Assessment |
| ||
| Urinary frequency | Renal and urinary disorders | Non-systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Hossein Borghaei, DO, MS | Fox Chase Cancer Center | 215-214-4297 | Hossein.Borghaei@fccc.edu |
| Dec 1, 2021 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D012008 | Recurrence |
| D002289 | Carcinoma, Non-Small-Cell Lung |
| ID | Term |
|---|---|
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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Not provided
| ID | Term |
|---|---|
| D000077269 | Lenalidomide |
| C582435 | pembrolizumab |
| ID | Term |
|---|---|
| D010797 | Phthalimides |
| D010795 | Phthalic Acids |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D010881 | Piperidones |
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D054833 | Isoindoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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