Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Neuroendocrine

Prostatic Neoplasms

Carcinoma, Small Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Adenocarcinoma

Neoplasms, Nerve Tissue

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Bendamustine Hydrochloride

Immunomodulating Agents

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Patients undergo leukapheresis to obtain PBMCs for T cell product manufacturing and may undergo bridging therapy at the discretion of the treating clinician on study. Patients then undergo lymphodepleting chemotherapy with cyclophosphamide IV and fludarabine IV on days -5, -4 and -33 or single agent bendamustine on days -4 and -3 at the discretion of the treating clinician and/or PI. Patients receive an autologous L1CAM-specific CAR+EGFRt+ T cells infusion on day 0. Based on disease response and persistence of CAR T cells, patients may receive additional lymphodepletion chemotherapy and an autologous L1CAM-specific CAR+EGFRt+ T cell infusion as soon as 6 weeks and no later than 24 weeks after the first infusion, or at the discretion of the PI. Patients also undergo ECHO or MUGA during screening. Patients undergo x-ray imaging, CT, bone scan, and blood sample collection throughout the trial. Additionally, patients may undergo tissue biopsy on the trial.

Bendamustine

Biopsy

Biospecimen Collection

Bone Scan

Bridge Therapy

Computed Tomography

Echocardiography

Leukapheresis

Multigated Acquisition Scan

Given autologous L1CAM-specific CAR+EGFRt+ T cells IV

T-cell Receptor-engineered T-cells

X-Ray Imaging

Fred Hutch Intake

Michael Schweizer

This phase I trial studies the side effects and best dose of autologous CD8+ and CD4+ lentivirally transduced to express L1CAM-specific chimeric antigen receptor (CAR) and EGFRt mutation specific T cells and to see how well they work in treating patients with small cell neuroendocrine prostate cancer (SCNPC) that has spread to nearby tissue or lymph nodes (locally advanced) and cannot be removed by surgery (unresectable) or has spread from where it first started (primary site) to other places in the body (metastatic). CAR T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack tumor cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's tumor cells is added to the T cells in the laboratory. Some solid tumor cells have an L1CAM protein on their surface, and T cells can be modified with a receptor, called a chimeric antigen receptor (CAR), to help recognize this protein and kill these tumor cells. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. These L1CAM mutation specific T cells may help the body's immune system identify and kill L1CAM locally advanced and unresectable or metastatic small cell neuroendocrine prostate cancers' tumor cells.

OUTLINE: This is a dose-escalation study of autologous L1CAM-specific CAR+EGFRt+ T cells.

Patients undergo leukapheresis to obtain peripheral blood mononuclear cells (PBMCs) for T cell product manufacturing and may undergo bridging therapy at the discretion of the treating clinician on study. Patients then undergo lymphodepleting chemotherapy with cyclophosphamide intravenously (IV) and fludarabine IV on days -5, -4 and -33 or single agent bendamustine on days -4 and -3 at the discretion of the treating clinician and/or principal investigator (PI). Patients receive an autologous L1CAM-specific CAR+EGFRt+ T cell infusion on day 0. Based on disease response and persistence of CAR T cells, patients may receive additional lymphodepletion chemotherapy and an autologous L1CAM-specific CAR+EGFRt+ T cell infusion as soon as 6 weeks and no later than 24 weeks after the first infusion, or at the discretion of the PI. Patients undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening. Patients undergo x-ray imaging, computed tomography (CT), bone scan, and blood sample collection throughout the trial. Additionally, patients may undergo tissue biopsy on the trial.

After completion of study treatment, patients are followed up monthly for 3 months, then every 3 months up to 12 months then may undergo long-term follow-up annually for up to 15 years.

Autologous T Cells Lentivirally Transduced to Express L1CAM-Specific Chimeric Antigen Receptors in Treating Patients With Locally Advanced and Unresectable or Metastatic Small Cell Neuroendocrine Prostate Cancer

A Phase I Safety and Feasibility Study of Cellular Immunotherapy for Extensive Stage Small Cell Neuroendocrine Prostate Cancer Using Autologous T Cells Lentivirally Transduced to Express L1CAM-Specific Chimeric Antigen Receptor

The toxicities observed at each dose level will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0 and nadir or maximum values for the laboratory measures), date of onset and attribution. Tables will be created to summarize these toxicities and side effects by dose level.

The toxicities observed at each dose level will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by NCI CTCAE version 5.0 and nadir or maximum values for the laboratory measures), date of onset and attribution. Tables will be created to summarize these toxicities and side effects by dose level.

Will be determined using RECIST version 1.1 and will be summarized at each dose level, and the number and percent responding combined across dose levels.

Will be assessed using RECIST v 1.1 criteria for soft tissue metastases and Prostate Cancer Working Group 3 criteria. Survival and time to relapse/progression will be summarized both by pooling across dose levels and within each dose level. Will calculate survival curves and the median expected survival duration, using the Kaplan-Meier estimate.

Bristol-Myers Squibb

Fred Hutchinson Cancer Center

Blood and Lymph Conditions

Immune System Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Lymphosarcoma

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Dermatologic Agents

Reproductive Control Agents

Anti-Infective Agents

Micronutrients

Hematinics

Vitamins

Dexamethasone

Doxorubicin

Liposomal doxorubicin

Methotrexate

Vincristine

Bortezomib

Dexamethasone acetate

Pegaspargase

Asparaginase

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Enzyme Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antimetabolites

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Tubulin Modulators

Antimitotic Agents

Folinic Acid

Folate

Vitamin B9

Patients with refractory or relapsed acute lymphoblastic leukemia will receive one-two courses of salvage regimen composed by:

* Bortezomib 1.3 mg/m2 I.V. D1,D4,D8,D11;
* Vincristine 1.5 mg/m2 I.V. (maximum at 2 mg) - D1, D8,D15,D22;
* Doxorubicin 60 mg/m2 I.V. - D1;
* Peg-asparaginase 2000 IU/m2 I.V. - D4 and D18;
* Dexamethasone 20 mg/m2 P.O. or I.V. (divided BID) - D1-D5 and D15-D19
* Intrathecal chemotherapy: methotrexate 12 mg + dexamethasone 2 mg.

Patients should receive one or two courses of this regimen, aiming to achieve complete remission as a bridge to proceed with allogeneic HSCT.

Graziela S Silva

Bruna Moraes, MSc

Wellington F Silva, MD PhD

Wellington Silva, MD PhD

This is a interventional phase II study aiming to examine the complete response rate of a bortezomib-based salvage regimen in adults with refractory or relapsed acute lymphoblastic leukemia (ALL), seeking to compare outcomes with the available literature and with our historical data on relapsed/refractory ALL.

Acute lymphoblastic leukemia (ALL) is a rare neoplasm in adults, with long-term survival rates approaching 50% with current regimens. Although high rates of complete response are achieved with the first-line therapy, many patients are primary refractory or may further relapse. Arguably, these patients have a more resistant disease with higher risk genetic alterations and a much less likely to be cured, which almost always only can be obtained by a following allogeneic hematopoietic stem-cell transplantation (HSCT). Therefore, strategies to salvage patients with detectable disease after induction blocks or with relapsed disease are crucial to prolong survival and potentially cure those patients, working as a bridge therapy to HSCT. Historically, patients with relapsed/refractory ALL have received multidrug regimens based on high-dose cytarabine, such as fludarabine, cytarabine and idarubicin (FLAG-IDA). Those regimens provide a 30-40% complete response rate with non-negligible toxicity. Recently, new targeted agents such as blinatumomab, inotuzumab, and cellular therapies have arisen for B-lineage disease, even though these agents are not available in the public health setting. Previous studies have tested salvage regimens for ALL encompassing proteasome inhibitors plus highly synergistic drugs (dexamethasone, vincristine, asparaginase, doxorubicin), with exciting outcomes in limited case series. For adults, these regimens are less studied. However, preliminary data suggest that they are less toxic and more potent since patients can receive different drug combinations that they had not been exposed to before. The primary objective of this study is to examine the complete response rate of this regimen in our population, aiming to compare with the available literature and with our historical data on relapsed/refractory ALL. Secondary objectives are:

1. To determine the safety and feasibility of a bortezomib-based regimen for salvage relapsed/refractory ALL in our setting.
2. To determine the rate of patients who are able to proceed with HSCT after the treatment.
3. To calculate event-free survival and overall survival after the salvage regimen for relapsed/refractory ALL.
4. To calculate the rate of measurable residual disease (MRD) negative status after the treatment.
5. To examine the rate of febrile neutropenia, liver toxicity, neurotoxicity, and treatment-related mortality after this regimen in relapsed/refractory ALL.

Bortezomib-based Regimen for Refractory or Relapsed Acute Lymphoblastic Leukemia

Bortezomib-based Regimen for Refractory or Relapsed Acute Lymphoblastic Leukemia in Adults

Disappearance of lymphoid blasts in peripheral blood, with fewer than 5% of lymphoid blasts quantified in the bone marrow aspirate through immunophenotyping.

Time interval between study enrollment and the occurrence of an event (non-response, relapse, or death) or last follow-up (censorship).

Time interval between study enrollment and the occurrence of death or last follow-up (censorship).

Absence of pathological lymphoid blasts in a bone marrow sample detected through immunophenotyping with a minimum sensitivity of 10-4.

Proportion of patients who successfully underwent allogeneic hematopoietic stem-cell transplantation after the study therapy

Libbs Farmacêutica LTDA

Instituto do Cancer do Estado de São Paulo

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Autologous T Cells Lentivirally Transduced to Express L1CAM-Specific Chimeric Antigen Receptors in Treating Patients With Locally Advanced and Unresectable or Metastatic Small Cell Neuroendocrine Prostate Cancer	NCT06094842	Prostate Carcin... Prostate Small ... Stage III Prost... Stage IV Prosta...	Bendamustine Biopsy Biospecimen Col... Bone Scan Bridge Therapy Computed Tomogr... Cyclophosphamid... Echocardiograph... Fludarabine Leukapheresis Multigated Acqu... T-cell Receptor... X-Ray Imaging	18 Years -	Fred Hutchinson Cancer Center
Bortezomib-based Regimen for Refractory or Relapsed Acute Lymphoblastic Leukemia	NCT06034561	Acute Lymphobla... Acute Lymphobla...	Bortezomib	16 Years - 60 Years	Instituto do Cancer do Estado de São Paulo

Spots Global Cancer Trial Database for bridge therapy