Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

All Drugs and Chemicals

Vaccines

* Vaccines will be weeks 1, 5, 9, 13, 17, and 21. Vaccines will occur within +/- 1 week with at least 3 weeks between vaccines. All study injections will be given intramuscularly using TDS-IM system. At each vaccination time point, patients will receive 2 injections of the neoantigen DNA vaccine, 1 injection into each deltoid or lateralis.
* Minimum observation of 30 minutes. Vital signs will be taken at 30-45 minutes post-immunization. The injection sites will be inspected for evidence of local reaction. Follow up on subject well-being will be performed by telephone on the 1st or 2nd day following each injection. -Post-vaccination follow-up visits are at Week 25 ± 7 days and Week 77 ± 14 days. Additional follow-up visits or telephone contact will be scheduled at Week 129 and annually thereafter if the patient is alive and available for follow-up.
* At intervals throughout the study (both before and after vaccination) subjects will have blood drawn for immunologic assays.

-Personalized polyepitope inserts integrating the prioritized neoantigens and mesothelin epitopes will be designed and then synthesized and cloned into the pING parent vector

Personalized neoantigen DNA vaccine

TDS-IM Electrode Array System

-Enrollment, mid adjuvant chemotherapy, end of chemotherapy, week 1, week 5, week 9, week 13, week 17, week 21, week 25, and week 77

Peripheral blood draws

William Gillanders, M.D.

Daniel Laheru, M.D.

This is a phase 1 open-label study to evaluate the safety and immunogenicity of a neoantigen DNA vaccine strategy in pancreatic cancer patients following surgical resection and adjuvant chemotherapy. The neoantigen DNA vaccines will incorporate prioritized neoantigens and personalized mesothelin epitopes and will be administered with an electroporation device. The hypothesis of this study is that neoantigen DNA vaccines will be safe and capable of generating measurable neoantigen-specific CD4 and CD8 T cell responses.

-Subjects will be enrolled within 12 weeks of surgery and standard of care adjuvant chemotherapy will last approximately 12 weeks with an additional 12 weeks of standard of care adjuvant chemotherapy or adjuvant chemoradiation. The first vaccine may be administered following confirmation of disease-free status and within 60 days following date of repeat imaging. From time of enrollment to first vaccine could be up to 45 weeks.

Neoantigen DNA Vaccine in Pancreatic Cancer Patients Following Surgical Resection and Adjuvant Chemotherapy

A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of a Neoantigen DNA Vaccine Strategy in Pancreatic Cancer Patients Following Surgical Resection and Adjuvant Chemotherapy

* Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0
* Related indicates possibly, probably, or definitely related to the study treatment

Immunogenicity is defined as the number of participants with a neoantigen-specific immune response measured by ELISPOT analysis. A participant is considered a responder if there is a significant increase in the number of neoantigen-specific T cells to at least one neoantigen after vaccination. A significant increase is based on t-test comparing the number of neoantigen-specific T-cells before and after vaccination with p=0.05 for significance.

National Cancer Institute (NCI)

Washington University School of Medicine

Personalized Neoantigen DNA Vaccine

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Abdominal pain

Bruising

Chills

Conjunctivitis

Fatigue

Fever

Injection site pain

Injection site reaction

Hypertension

Muscle soreness

Myalgia

Nausea

Pain

Safety of Neoantigen DNA Vaccine as Measured by the Number of Subjects Experiencing Each Type of Treatment-related Adverse Event

Participants who are not included in this outcome measure include one who did not have enough tissue, one who had poor quality RNA and a vaccine could not be developed, and 2 who developed disease progression.

Immunogenicity of the Neoantigen DNA Vaccine as Measured by ELISPOT Analysis

The multiparametric flow cytometry assay described in the protocol was not sufficiently sensitive to reliably detect neoantigen-specific T cell responses. Additional flow cytometry assays are being performed as an exploratory objective.

Immunogenicity of the Neoantigen DNA Vaccine as Measured by Multiparametric Flow Cytometry

Overall Study

Blood and Lymph Conditions

Immune System Diseases

Lymphoma, Large B-Cell, Diffuse

Lymphoma

Lymphoma, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Lymphosarcoma

Antineoplastic Agents

Anti-Infective Agents

Dermatologic Agents

Amino Acids

Blinatumomab

Antibodies

Etoposide

Cytarabine

Melphalan

Etoposide phosphate

Podophyllotoxin

Immunoglobulins

Carmustine

Mechlorethamine

Alkylating Agents

Enzyme Inhibitors

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Phenylalanine

* Standard of care ASCT with BEAM conditioning (carmustine/etoposide/cytarabine/melphalan) - guidelines below, other conditionings are allowed:

  * carmustine is typically given intravenously (IV) at a dose of 300 mg/m\^2 on Day -7
  * etoposide is typically given IV at a dose of 100 mg/m\^2 twice per day (BID) on Days -6, -5, -4, and -3 (8 doses)
  * cytarabine is typically given IV at a dose of 100 mg/m\^2 BID on Days -6, -5, -4, and -3 (8 doses)
  * melphalan is typically given IV at a dose of 140 mg/m\*2 on Day -2
* Auto-SCT will take place on Day 0 as per institutional guidelines
* Consolidation with blinatumomab will start 6 weeks following auto-SCT. Patients with CR or PR based on pre-transplant PET/CT will receive blinatumomab as a continuous IV infusion (CIVI) at 9μg/day for 1 week, then 28μg/day for 3 weeks (total of 4 weeks).

-Blinatumomab is a bispecific T cell engaging antibody

Autologous stem cell transplant

-Carmustine is an alkylating agent. It will be sourced from commercial supply. Institutional guidelines will be followed for storage, preparation, and administration of carmustine.

-Etoposide is a semi-synthetic podophyllotoxin derivative. It will be sourced from commercial supply. Institutional guidelines will be followed for storage, preparation, and administration of etoposide.

-Cytarabine, commonly known as Ara-C, is a synthetic nucleoside. It will be sourced from commercial supply. Institutional guidelines will be followed for storage, preparation, and administration of cytarabine.

-Melphalan is an alkylating agent. It will be sourced from commercial supply. Institutional guidelines will be followed for storage, preparation, and administration of melphalan.

-Day +42, Day + 43, Day +56, and Day +100

Armin Ghobadi, M.D.

Based on the further need to improve progression-free survival (PFS) and overall survival (OS) post autologous stem cell transplant (SCT) for DLBCL, the hematopoietic profile of patients following auto-SCT, the activity of blinatumomab in DLBCL and its favorable toxicity profile, the investigators propose a pilot study to test blinatumomab as consolidation therapy post auto-SCT for patients with DLBCL.

The investigators hypothesize the blinatumomab consolidation will optimize the effector to target (E-T) ratio and aid in the eradication of remaining tumor cells, leading to decreased relapse and increased overall survival. In addition, since tumor burden will be at a minimum, infusional toxicities including neurologic toxicities may also be limited. The purpose of this pilot study is to study the feasibility and tolerability of blinatumomab consolidation post auto-SCT for patients with chemo-sensitive DLBCL undergoing auto-SCT.

Blinatumomab Consolidation Post Autologous Stem Cell Transplantation in Patients With Diffuse Large B-Cell Lymphoma (DLBCL)

A Pilot Trial of Blinatumomab Consolidation Post Autologous Stem Cell Transplantation in Patients With DLBCL

-The primary endpoint is calculated by the proportion of patients who complete a full course of blinatumomab to the total number of patients started blinatumomab after auto-SCT.

-PFS is defined as from the date of Day 0 to date of progression or death, which occurs first. They are censored at the last follow-up otherwise.

-OS is defined as from the date of Day 0 to date of death. They are censored at the last follow-up otherwise.

-Complete remission=disappearance of all evidence of disease

Amgen

Lymphoma, Follicular

Follicular Lymphoma

Antirheumatic Agents

Gastrointestinal Agents

Nivolumab

Rituximab

Poly ICLC

Complement C3

Complement C3d

Poly I-C

Carboxymethylcellulose Sodium

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Interferons

Laxatives

Cathartics

* All cycles are 4 weeks (wks), with nivolumab every 2 wks during Cycles 1-6 \& every 4 wks during Cycles 7-12 \& vaccine on Cycle 1 Days 1, 4, 8, 15; Cycle 2 Day 1; and then on Day 1 of Cycles 4, 6, 8, 10, 12
* After 2 cycles, restaging will be performed, \& patients with CR, PR, or SD will continue on nivolumab + vaccine. Patients with evidence of PD may initiate anti-CD20 mAb therapy (drug to be determined by the treating physician) weekly for 4 wks during Cycle 3, followed by a dose on Day 1 of every other cycle (Cycles 6, 8, 10, and 12).
* After 6 cycles, restaging will be performed again, and patients with CR, PR, or SD will continue nivolumab + vaccine. Patients with PD at that time point (but not treated with anti-CD20 mAb therapy thus far on this protocol) will initiate anti-CD20 mAb (drug to be determined by the treating physician) therapy weekly for 4 wks during Cycle 7, followed by a dose Day 1 of Cycles 10 \& 12 \& 2 additional doses 8 wks apart.

* Cycle 12 vaccine administration is optional
* The peptides comprising the vaccine are reconstituted in up to 4 pools with 5 peptides per pool (A, B, C, and D) . At each vaccination time point, each of the up to four pools will be administered to one of the four limbs (A - Right Arm, B - Left Arm, C - Right Leg, D - Left Leg) by subcutaneous injection.

Personalized tumor vaccine

-The personalized tumor vaccine will be co-administered with poly-ICLC.

-Nivolumab will be administered at a dose of 240 mg intravenously

-Time of biopsy, during the pre-treatment check (any time before cycle 1 day 1), Cycle 1 Day 15, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 6 Day 1, Cycle 12 Day 1, Time of response, and Time of progression or relapse

* Prior to the initiation of treatment and up to five days prior to treatment on cycle 6 day 1, patients will undergo apheresis according to standard institutional procedures for non-mobilized collection.
* Peripheral blood leukocytes will be cryopreserved for later assessment for the presence of T-cells that recognize tumor specific mutant antigens and immunophenotype, and the presence of other lymphocytes or regulatory populations.

Leukapheresis

-Other anti-CD20 mAb treatment can be used

-Biopsies on lymph node or extranodal site(s) are to be obtained at: screening (only after the patient is deemed eligible; during cycle 2 (after treatment on C2D15 and prior to treatment on C3D1); disease relapse or progression (if this occurs)

Biopsy

Nancy Bartlett, M.D.

Follicular lymphoma (FL) has a number of effective standard of care therapies; however, FL is not currently considered curable. Therefore, designing well tolerated therapies without cumulative and long-term toxicity is critical. This is a pilot safety and feasibility study that combines a personalized tumor vaccine with nivolumab for the treatment of FL. Patients who demonstrate progression on this study may be treated with rituximab (or another monoclonal antibody against CD20) in addition to vaccine therapy with nivolumab at the discretion of treating physician if clinically indicated.

For the first three patients treated on study therapy, treatment of each subsequent patient will not be allowed until the prior patient has completed Cycle 1. If no unexpected adverse events attributed to the combination therapy are observed, after the third patient completes Cycle 1, treatment initiation may occur without restrictions for the remaining patients.

Personalized Tumor Vaccine Strategy and PD-1 Blockade in Patients With Follicular Lymphoma

Pilot Study of a Personalized Tumor Vaccine Strategy and PD-1 Blockade in Patients With Follicular Lymphoma

-Unacceptable toxicity will be described as inability to receive further therapy due to toxicities of therapy as defined by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 or the occurrence of other toxicities deemed to be at sufficiently high risk to patients by the principal investigator

* ORR = number of participants with complete response + number of participants with partial response
* Overall response rates will be compared between participants who received anti-CD20 mAb treatment (rituximab) versus those participants who did not receive anti-CD20 mAb treatment

* CR rates will be compared between participants who received anti-CD20 mAb treatment (rituximab) versus those participants who did not receive anti-CD20 mAb treatment
* CR:

  * Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy.
  * London Deauville score of 1 and 2 in lymph nodes and extra lymphatic sites is considered to represent complete metabolic response. A London Deauville score 3 in the post treatment PET scan may be considered to represent complete metabolic response especially if it is not higher than the surrounding normal physiologic uptake.
  * No evidence of FDG avid disease in the bone marrow
  * No new lesions
  * If the bone marrow was involved by lymphoma before treatment, the infiltrate must have cleared on repeat bone marrow biopsy.

* Duration of responses will be compared between participants who received anti-CD20 mAb treatment (rituximab) versus those participants who did not receive anti-CD20 mAb treatment
* Duration of response = time from first vaccine dose to first evidence of disease progression in participants with at least one response of CR, PR, or SD

* PFS will be compared between participants who received anti-CD20 mAb treatment (rituximab) versus those participants who did not receive anti-CD20 mAb treatment
* PFS: time from first CR, PR, or SD response to disease progression, death, or last follow-up
* PD:

  * London Deauville score of 4 or 5 in individual target nodes/masses with an increase in intensity of uptake from the baseline and/or new FDG avid foci consistent with lymphoma at interim or end of treatment assessment
  * New FDG avid foci of extranodal disease consistent with lymphoma. If there is concern regarding the etiology of the new lesions, biopsy or interval scan may be considered.
  * New or recurrent FDG avid foci in the bone marrow

* OS will be compared between participants who received anti-CD20 mAb treatment (rituximab) versus those participants who did not receive anti-CD20 mAb treatment
* OS: time from first vaccine dose to death or last follow-up

* Partial response rates will be compared between participants who received anti-CD20 mAb treatment (rituximab) versus those participants who did not receive anti-CD20 mAb treatment
* PR:

  * London Deauville score of 4 or 5 in lymph nodes and extra lymphatic sites with reduced uptake compared with the baseline and residual mass(es) of any size on interim scan
  * Residual bone marrow uptake higher than the uptake in the normal marrow but reduced when compared with baseline If there are persistent focal changes in the marrow in the context of a nodal response consideration should be given to further evaluation with MRI or biopsy or an interval scan
  * No new lesions

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Small Cell Lung Carcinoma

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Small Cell Lung Cancer

Carboplatin

Durvalumab

* Patients will receive durvalumab (1500mg Q3W) in combination with standard of care carboplatin and etoposide for a total of 4 cycles given every 3 weeks
* Beginning 4 weeks following Cycle 4 of carboplatin/etoposide/durvalumab, patients on will then receive 6 cycles of durvalumab 1500 mg with the polyepitope neoantigen DNA vaccine, both administered once every 4 weeks
* Patients may then receive durvalumab every 4 weeks until disease progression or drug toxicity
* Should a delay in vaccine preparation occur, patients will begin durvalumab and the vaccine will be added with the subsequent cycle.

All study injections will be given intramuscularly using an integrated electroporation device (TDS-IM system, PapiVax Biotech). At each vaccination time point, patients will receive two injections of the neoantigen DNA vaccine, one injection into each deltoid or lateralis.

Neoantigen DNA vaccine

-Integrated electroporation administration system

TDS-IM v2.0 Device

-Pre-treatment, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Vaccine Day 1, Vaccine Day 29, Vaccine Day 85, Vaccine Day 141, on even numbers of cycles for durvalumab for one year following completion of vaccine

Jeffrey Ward, M.D., Ph.D.

Ramaswamy Govindan, M.D.

Saiama Waqar, M.D.

Daniel Morgensztern, M.D.

Maria Baggstrom, M.D.

The investigators hypothesize that a personalized neoantigen vaccine combined with durvalumab will improve the progression free survival of patients with extensive state small cell lung cancer (ES-SCLC).

Personalized Neoantigen Vaccine in Combination With Durvalumab (MEDI4736) in Extensive Stage Small Cell Lung Cancer

Phase II Study of a Personalized Neoantigen Vaccine in Combination With Durvalumab (MEDI4736) in Extensive Stage Small Cell Lung Cancer

All study data will be shared with the study sponsor and will be available from presentations and upon publication.

-Safety and tolerability will be measured by National Cancer Institute Common Terminology Criteria (NCI CTCAE) v 5.0

-Feasibility is defined as the ability to produce a vaccine for 80% of patients enrolled

* PFS is defined as the duration of time from start of durvalumab to time of progression or death, whichever occurs first.
* Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).

-The response conversion rate is defined as the proportion of patients who improve in RECIST v1.1 category subsequent to vaccination.

-The duration of response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).

-Defined as time from start of durvalumab to death due to any causes

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Neoantigen DNA Vaccine in Pancreatic Cancer Patients Following Surgical Resection and Adjuvant Chemotherapy	NCT03122106	Pancreatic Canc... Pancreas Cancer Cancer of the P...	Personalized ne... TDS-IM Electrod... Peripheral bloo...	18 Years -	Washington University School of Medicine
Blinatumomab Consolidation Post Autologous Stem Cell Transplantation in Patients With Diffuse Large B-Cell Lymphoma (DLBCL)	NCT03072771	Diffuse Large B...	Blinatumomab Autologous stem... Carmustine Etoposide Cytarabine Melphalan Peripheral bloo...	18 Years -	Washington University School of Medicine
Personalized Tumor Vaccine Strategy and PD-1 Blockade in Patients With Follicular Lymphoma	NCT03121677	Follicular Lymp...	Personalized tu... Poly ICLC Nivolumab Peripheral bloo... Leukapheresis Rituximab Biopsy	18 Years -	Washington University School of Medicine
Personalized Neoantigen Vaccine in Combination With Durvalumab (MEDI4736) in Extensive Stage Small Cell Lung Cancer	NCT04397003	Extensive-stage...	Neoantigen DNA ... Durvalumab TDS-IM v2.0 Dev... Peripheral bloo...	18 Years -	Washington University School of Medicine
Personalized Neoantigen Vaccine in Combination With Durvalumab (MEDI4736) in Extensive Stage Small Cell Lung Cancer	NCT04397003	Extensive-stage...	Neoantigen DNA ... Durvalumab TDS-IM v2.0 Dev... Peripheral bloo...	18 Years -	Washington University School of Medicine

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