Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Breast Neoplasms

Pancreatic Neoplasms

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Breast Diseases

Skin Diseases

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Atezolizumab

Immunomodulating Agents

Durvalumab

Ibrutinib

Antineoplastic Agents, Immunological

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

In the Phase 1b (safety portion) of the study, a starting dose of 560 mg of ibrutinib and 10 mg/kg of MEDI4736 will be explored and will follow a 6+3 dose de-escalation design and will include a sentinel participant which will have a 3-day observation period prior to dosing of subsequent participants. Participants with one of the following three tumor types will be eligible for enrollment: NSCLC (adenocarcinoma and squamous-cell carcinoma), Breast cancer (triple-negative and HER2-positive cancer), and Pancreatic cancer (adenocarcinoma).

Participants with one of three solid tumor types (Stage III/IV) will be enrolled in the Phase 2 portion of this protocol: NSCLC (adenocarcinoma and squamous-cell carcinoma), Breast cancer (triple-negative and HER2-positive cancer), and Pancreatic cancer (adenocarcinoma) and treated at the R2PD of ibrutinib and durvalumab determined in Phase 1b. An interim analysis will be performed to evaluate the response and the safety profile, and the study may be discontinued based on the interim efficacy and/or safety results.

Isaiah Dimery

This is a Phase 1b/2, multi-center study to assess the safety and efficacy of ibrutinib in combination with durvalumab (MEDI4736) in participants with relapsed or refractory solid tumors.

A Multi-Center Study of Ibrutinib in Combination With MEDI4736 in Subjects With Relapsed or Refractory Solid Tumors

A Multi-Center Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, in Combination With Durvalumab (MEDI4736), in Subjects With Relapsed or Refractory Solid Tumors

Cmax = the peak (maximum) plasma concentration of ibrutinib during the dosing interval on Cycle 3 Day 1.

AUC0-24 = the area under the plasma concentration-time curve of ibrutinib during the dosing interval on Cycle 3 Day 1

Cmax = the peak (maximum) plasma concentration of durvalumab (MEDI4736) after administration on Cycle 6 Day 1.

Ctrough = the trough plasma concentration of durvalumab (MEDI4736) after administration on Cycle 6 Day 1

BTK binding site occupancy of ibrutinib was measured from peripheral blood samples collected from participants during Cycle 3 Day 1.

Pharmacyclics LLC.

Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.

All subjects who received at least one dose of study treatment.

Phase 1b/2

All participants who received at least one dose of study treatment.

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Baseline analysis population includes all patients that received at least one dose of study treatment.

Thorsten Graef

In the Phase 1b (safety portion) of the study, a starting dose of 560 mg of ibrutinib and 10 mg/kg of MEDI4736 will be explored and will follow a 6 + 3 dose de-escalation design and will include a sentinel participant which will have a 3-day observation period prior to dosing of subsequent participants. Participants with one of the following three tumor types will be eligible for enrollment: NSCLC (adenocarcinoma and squamous-cell carcinoma), breast cancer (triple-negative and HER2-positive cancer), and Pancreatic cancer (adenocarcinoma).

Phase 1b

Phase 1b: Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Ibrutinib and Durvalumab (MEDI4736) and to Find the Recommended Phase II Dose.

Participants with one of three solid tumor types (Stage III/IV) will be enrolled in the Phase 2 portion of this protocol: NSCLC (adenocarcinoma and squamous-cell carcinoma), breast cancer (triple-negative and HER2-positive cancer), and pancreatic cancer (adenocarcinoma) and treated at the R2PD of ibrutinib and durvalumab determined in Phase 1b. An interim analysis will be performed to evaluate the response and the safety profile, and the study may be discontinued based on the interim efficacy and/or safety results.

Phase 2

The Response-evaluable population was participants who received at least 1 dose of treatment (ibrutinib and durvalumab) and provided 1 post-baseline response assessment.

Phase 2: Efficacy of Ibrutinib in Combination With Durvalumab (MEDI4736) in Participants With Relapsed or Refractory Solid Tumors by Assessing the ORR Per RECIST 1.1.

All participants who received at least one dose of study treatment and had evaluable pharmacokinetic data.

Phase 1b/2 (Pharmacokinetic Population)

All participants who received at least one dose of study treatment and had evaluable pharmacokinetic data. Data were analyzed together for Phase 1b and Phase 2 because the dose was the same.

Phase 1b/2: Pharmacokinetics (Cmax) of Ibrutinib

All participants who received at least one dose of study treatment and had evaluable pharmacokinetic data. Data were analyzed together for Phase 1b/2 because the dose was the same.

Phase 1b/2: Pharmacokinetics (AUC0-24h) of Ibrutinib

Phase 1b/2: Pharmacokinetics (Cmax) of Durvalumab (MEDI4736)

Phase 1b/2: Pharmacokinetics (Ctrough) of Durvalumab (MEDI4736)

Phase 1b: Pharmacodynamics

Participants who enrolled and received at least 1 dose of study treatment.

Phase 2: Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Ibrutinib and Durvalumab (MEDI4736)

All subjects who received at least one dose of ibrutinib and who had at least one evaluable BTK occupancy assay result at Cycle 3 Day 1.

Phase 2: Pharmacodynamics

Period 1

Period 2

Symptoms and General Pathology

Recurrence

Vaccines

Tumor treatment vaccine(TTV) would be given deep subcutaneously in the arm or near the tumor.The check indexes are image examination (CT, MRI or PET scan) and blood tests (including tumor markers, lymphocyte subsets and circulating tumor cell).

Patients will receive tumor treatment vaccine(TTV), which would be given deep subcutaneously in the arm or near the tumor.The initial dose is 1ml / week, if the reaction isn't obvious, the dose can be appropriately increased to 2.5-4.0ml / week.The interval between injections can be shortened or extended depending on the patient's condition and response.The duration of treatment should be extended as long as possible, at least 6-12 months.

tumor treatment vaccine injection

Peihua Lu, Doctor

This is a study of the clinical efficacy and mechanism study of tumor treatment vaccine (TTV, also known as Neo-BCV) in patients with recurrent and refractory advanced solid tumors.

The study aims to explore the safety and effectiveness of Neo-BCV in the treatment of advanced solid tumors.The safety will be evaluated by statistics of adverse reactions. The efficacy will be evaluated according to local relief degree, progress free survival (PFS) and overall survival (OS).

A Clinical Study on the Efficacy and Mechanism of Tumor Treatment Vaccine (TTV) for Recurrent and Refractory Advanced Solid Tumors

The Efficacy and Safety of Tumor Treatment Vaccine in Patients With Advanced Solid Tumors

It will be evaluated by the Response Evaluation Criteria in Solid Tumors（RECIST1.1）

The duration from the beginning of treatment to cancer recurrence or progression

The duration from the beginning of treatment to patient death

Wuxi People's Hospital

Blood and Lymph Conditions

Immune System Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

Syndrome

Lymphoma

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Hematologic Neoplasms

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Hodgkin Disease

Preleukemia

Myelodysplastic Syndromes

Wilms Tumor

Lymphoma, Non-Hodgkin

Acute Disease

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Bone Marrow Diseases

Precancerous Conditions

Disease Attributes

Myeloproliferative Disorders

Chronic Disease

Myeloid Leukemia

Acute Myeloid Leukemia

Lymphosarcoma

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Graft Versus Host Disease

Acute Non Lymphoblastic Leukemia

Chronic Myeloid Leukemia

Hodgkin Lymphoma

Acute Graft Versus Host Disease

Wilms' Tumor

Chronic Myeloproliferative Disorders

Antipyretics

Analgesics

Anti-Allergic Agents

Antiemetics

Central Nervous System Depressants

Gastrointestinal Agents

Dermatologic Agents

Antirheumatic Agents

Acetaminophen

Molgramostim

Sargramostim

Diphenhydramine

Promethazine

Interleukin-4

Keyhole-limpet hemocyanin

Adjuvants, Vaccine

Analgesics, Non-Narcotic

Hypnotics and Sedatives

Anesthetics

Anesthetics, Local

Histamine H1 Antagonists

Histamine

Histamine phosphate

Histamine Antagonists

Neurotransmitter Agents

Adjuvants, Immunologic

Immunologic Factors

Related and unrelated donors undergo lymphapheresis to prepare cellular vaccines and to donate lymphocytes for infusion.

Participants receive donor lymphocytes and vaccines prepared from donors.

WT1 Peptide-Pulsed Dendritic Cells

Lymphocytes from donors (related or unrelated) collected via lymphapheresis.

Donor Lymphocytes

water-soluble protein; this study will use GMCSF (granulocyte macrophage colony stimulating factor)/IL-4 generated monocyte derived dendritic cells

IL-4

Neoantigen known to induce helper responses; will be used concurrently as a vaccine adjuvant and control antigen.

WT1 Peptides

Purified lipopolysaccharide prepared from E.Coli 0:113

Endotoxin

Terry J Fry, M.D.

Background:

* Most patients with acute lymphoblastic leukemia (ALL) and many patients with acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML) and non-Hodgkin's lymphoma (NHL) have a protein called Wilm's Tumor 1 (WT1) in their cancer cells. This protein is thought to be able to influence the growth of these cancers.
* A vaccine made with the WT1 protein may boost the immune system to help fight these cancers in patients whose cancer cells contain the protein.

Objectives:

* To determine the safety, effectiveness and side effects of giving the WT1 vaccine and donor white blood cells to patients with AML, ALL, CML or NHL who have previously received standard treatment and undergone stem cell transplantation.
* To determine the immune response to the WT1 vaccine and donor white blood cells in these patients and to determine if the response is related to the amount of WT1 protein in the patient's cancer cells.

Eligibility:

* Patients between 1 and 75 years of age with the blood antigen human leukocyte antigen (HLA-A2) and the WT1 cancer protein who have persistent or recurrent blood cancers after stem cell transplantation.
* The prior stem cell transplant donor must be willing to provide additional cells, which will be used to prepare the cellular vaccines and for donor lymphocyte (white blood cell) infusions.

Design:

* Patients are given the WT1 vaccine every 2 weeks for 6 weeks (weeks 0, 2, 4, 6, 8, 10). Each vaccination consists of two injections in the upper arm or thigh.
* On weeks 0, 4 and 8, patients also receive white blood cells from a donor to enhance the immune response. The cells are also given as a 15- to 30-minute infusion through a vein about 1 hour after the vaccine injection. Donor infusions are given only to patients with mild or no graft-vs-host disease resulting from their prior stem cell transplantation.
* Periodic physical examinations, blood and urine tests, scans to evaluate disease and other tests as needed are done for 12 months after enrollment in the study.

Background:

* Efforts to incorporate anti-tumor immunotherapy at stages of minimal residual disease (MRD) burden are limited by profound host immune depletion associated with standard anti-cancer therapies.
* Allogeneic blood and marrow stem cell transplantation (SCT) can be curative for a number of hematologic malignancies. Part of the success of this approach is an allogeneic immunologic reaction that has been demonstrated to play a role in the eradication of residual malignant disease after transplant in certain cancers (the so called graft-versus-leukemia, GVL, or graft-versus-tumor, GVT, effect). Nonetheless, relapse remains the primary cause of treatment failure after allogeneic SCT.
* The Wilm's tumor 1 (WT1) gene product is a tumor-associated antigen that represents a potential target for immunotherapy in a wide array of cancers. WT1 is expressed in most cases of acute leukemia and in many cases of chronic myelogenous leukemia and myelodysplastic syndromes. Importantly, WT1 has limited expression in normal tissues beyond embryogenesis. This trial represents an attempt to incorporate antigen-specific immunotherapy in the setting of allogeneic adoptive cell transfer.

Objectives:

* To determine the safety, toxicity, and feasibility of donor-derived dendritic cell vaccination and donor lymphocyte infusion (DLI) after allogeneic SCT.
* To determine the frequency and severity of graft-vs.-host disease (GVHD) in patients treated with peptide-loaded donor-derived dendritic cell vaccination and donor lymphocyte infusion (DLI).
* To evaluate whether immunologic responses to WT1-specific peptides can be generated by peptide-loaded donor-derived dendritic cell vaccination and DLI after allogeneic SCT.
* To evaluate whether clinical responses to WT1-specific peptides can be generated by peptide-loaded donor-derived dendritic cell vaccination and DLI after allogeneic SCT.
* To evaluate whether immunologic and/or clinical responses may be associated with the degree of WT1 expression by malignant cells or pre-existing donor anti-WT1 immunity.

Eligibility:

* HLA-A2 plus patients may be enrolled on this trial if they have relapsed or residual disease following allogeneic SCT for a WT1 expressing hematologic malignancy.
* Donors from the previous SCT, related or unrelated, must be 5- or 6- antigen genotypic HLA-matched (single HLA-A or B locus mismatch allowed) and HLAA2 plus.

Design:

* This is a pilot study, the primary aim of which is to assess safety and feasibility of this novel vaccine strategy aimed to enhance the GVL effect after allogeneic SCT.
* Donor-derived dendritic cells prepared from peripheral blood monocytes will be loaded with a combination of three WT1-derived peptides. These peptides are each comprised of one WT1-derived oligomeric epitope known to bind to HLA-A2 and an 11-mer protein transduction epitope known to enhance peptide loading and antigen presentation.
* Patients will receive donor-derived dendritic cell vaccines every 14 days for 6 doses. Donor leukocyte infusions (DLI) will also be administered with the vaccine.
* Study endpoints will include toxicity, feasibility, antigen-specific immunity, and disease response.
* This is an exploratory pilot trial. Up to 12 patients will be treated.
* Stopping rules will take effect if excessive toxicity (e.g., GVHD) or inability to generate vaccines are observed.

Wilm's Tumor 1 Protein Vaccine to Treat Cancers of the Blood

A Pilot Trial of WT1 Peptide-Loaded Allogeneic Dendritic Cell Vaccine and Donor Lymphocyte Infusion for WT1-Expressing Hematologic Malignancies

Here is the number of participants with adverse events. For details of the adverse events, see the adverse event module.

Acute Graft versus Host Disease (GVHD) was graded by the modified Glucksberg scale. 0 = no GVHD normal, 4 = severe GVHD.

Immune response was monitored by use of interferon gamma Enzyme-Linked Immunospot (ELISpot) and by delayed-type hypersensitivity (DTH) testing.

WT1 expression of the hematologic malignancy was confirmed by either having greater than 15% of malignant cells react with anti-WT1 by immunohistochemistry or by having a positive quantitative reverse transcription polymerase chain reaction (RT-PCR) of WT1 compared with a negative control.

WT1 expression of the hematologic malignancy was confirmed by either having greater than 15% of malignant cells react with anti-WT1 by immunohistochemistry or by having a positive quantitative reverse transcription polymerase chain reaction (RT-PCR) of WT1 compared with a negative control. DTH skin testing was performed using KLH and with a cocktail of WT1 peptides as 2 separate injections. Enzyme-Linked Immunospot (ELISpot) was performed against each peptide and was considered positive if results were at least 10 spots above background on at least 2 measurements. DTH was considered positive if there was at least .5cm induration 48 to 72 hours after placement.

KLH is a neoantigen known to induce helper response was used concurrently as a vaccine adjuvant and control antigen. DTH skin testing was performed using KLH and with a cocktail of WT1 peptides as 2 separate injections. Enzyme-Linked Immunospot (ELISpot) was performed against each peptide and was considered positive if results were at least 10 spots above background on at least 2 measurements. DTH was considered positive if there was at least .5cm induration 48 to 72 hours after placement.

Progressive disease is at least a 20% increase in the sum of the longest diameter of all target lesions (i.e. tumor response). Response criteria for acute leukemia's is worse marrow classification (i.e., M status) with at least a 50% increase in the percentage of marrow blasts, or no change in marrow classification (i.e., M status), but a 50% or greater increase in absolute peripheral blast count or extent of medullary disease

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Multi-Center Study of Ibrutinib in Combination With MEDI4736 in Subjects With Relapsed or Refractory Solid Tumors	NCT02403271	Non-Small Cell ... Breast Cancer Pancreatic Canc...	Ibrutinib Durvalumab	18 Years -	Pharmacyclics LLC.
A Clinical Study on the Efficacy and Mechanism of Tumor Treatment Vaccine (TTV) for Recurrent and Refractory Advanced Solid Tumors	NCT05747339	Solid Tumors, A...	tumor treatment...	18 Years - 75 Years	Wuxi People's Hospital
Wilm's Tumor 1 Protein Vaccine to Treat Cancers of the Blood	NCT00923910	Leukemia, Acute... Leukemia, Acute... Leukemia, Chron... Myelodysplastic... Non-Hodgkin's L...	WT1 Peptide-Pul... Donor Lymphocyt... IL-4 KLH WT1 Peptides Endotoxin Diphenhydramine Acetaminophen	1 Year - 74 Years	National Institutes of Health Clinical Center (CC)
A Clinical Study on the Efficacy and Mechanism of Tumor Treatment Vaccine (TTV) for Recurrent and Refractory Advanced Solid Tumors	NCT05747339	Solid Tumors, A...	tumor treatment...	18 Years - 75 Years	Wuxi People's Hospital
A Multi-Center Study of Ibrutinib in Combination With MEDI4736 in Subjects With Relapsed or Refractory Solid Tumors	NCT02403271	Non-Small Cell ... Breast Cancer Pancreatic Canc...	Ibrutinib Durvalumab	18 Years -	Pharmacyclics LLC.

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