Symptoms and General Pathology

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Recurrence

Melanoma

Carcinoma, Renal Cell

Kidney Neoplasms

Carcinoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Renal Cell Carcinoma

Neuroendocrine Tumor

Neuroepithelioma

All Drugs and Chemicals

Flt3 ligand protein

Adjuvants, Immunologic

Immunologic Factors

Protective Agents

Radiation-Protective Agents

recombinant CD40-ligand

recombinant flt3 ligand

Patrick Hwu, MD

RATIONALE: Biological therapies such as flt3L and CD40-ligand use different ways to stimulate the immune system and stop cancer cells from growing. Biological therapy may be an effective treatment for metastatic melanoma and metastatic kidney cancer.

PURPOSE: Phase I trial to study the effectiveness of flt3L combined with CD40-ligand in treating patients who have metastatic melanoma or metastatic kidney cancer.

OBJECTIVES: I. Determine the maximum tolerated dose of CD40-ligand when combined with fixed-dose flt3 ligand in patients with metastatic melanoma or renal cell cancer.

OUTLINE: This is a dose-escalation study of CD40-ligand. Patients receive fixed-dose flt3 ligand subcutaneously (SC) daily on days 1-14 and CD40-ligand SC daily on days 12-16. Treatment continues every 28 days for a maximum of 6 courses in the absence of unacceptable toxicity or disease progression. Cohorts of 3 to 6 patients receive escalating doses of CD40-ligand until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Patients with progressive disease after 2 courses may be eligible to receive high-dose interleukin-2 (IL-2) standard therapy.

PROJECTED ACCRUAL: A total of 5 patients were accrued for this study.

Biological Therapy in Treating Patients With Metastatic Melanoma or Metastatic Kidney Cancer

Treatment Of Patients With Metastatic Melanoma And Renal Cancer With A Combination Of Flt3L And CD40L

National Cancer Institute (NCI)

Blood and Lymph Conditions

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Leukemia, Myelomonocytic, Acute

Leukemia, Promyelocytic, Acute

Leukemia, Monocytic, Acute

Leukemia, Erythroblastic, Acute

Leukemia, Megakaryoblastic, Acute

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Acute Promyelocytic Leukemia

Acute Monoblastic Leukemia

Acute Myelomonocytic Leukemia

Acute Erythroid Leukemia

Di Guglielmo's Syndrome

Acute Megakaryoblastic Leukemia

Acute Myeloblastic Leukemia Without Maturation

Acute Myeloblastic Leukemia With Maturation

Jacob M. Rowe, MD

Richard A. Larson, MD

John E. Godwin, MD, MS

RATIONALE: Drugs such as flt3L may stimulate a person's immune system and help kill cancer cells. It is not yet known if flt3L is effective in treating acute myeloid leukemia.

PURPOSE: Randomized phase III trial to determine the effectiveness of flt3L in treating patients who have acute myeloid leukemia that is in remission.

OBJECTIVES:

* Compare the failure-free survival and overall survival in patients with acute myeloid leukemia in complete remission treated with maintenance flt3 ligand vs observation alone.
* Compare the long-term immunologic effects of these regimens in these patients.
* Compare the long-term safety and toxicity of these regimens in these patients.

OUTLINE: This is a randomized study. Patients are stratified according to complete remission (CR) (first vs second vs third or subsequent) and post-remission therapy (yes vs no). Patients are randomized to one of two treatment arms.

* Arm I: Patients receive flt3 ligand subcutaneously daily on days 1-14. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients undergo observation alone. Patients begin treatment or observation within 4 weeks after documentation of CR after induction therapy or within 4 weeks after discharge from hospital after post-remission therapy.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 139 patients will be accrued for this study within approximately 28 months.

flt3L in Treating Patients With Acute Myeloid Leukemia

A Phase III Study of Flt3 Ligand (Flt3L) Therapy in Acute Myeloid Leukemia (AML) Patients in Remission

Cancer and Leukemia Group B

SWOG Cancer Research Network

Eastern Cooperative Oncology Group

Infections

Carcinoma, Squamous Cell

Breast Neoplasms

Sarcoma

Osteosarcoma

Carcinoma, Merkel Cell

Breast Diseases

Neoplasms, Connective and Soft Tissue

Communicable Diseases

Polyomavirus Infections

Virus Diseases

DNA Virus Infections

Tumor Virus Infections

Carcinoma, Neuroendocrine

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Soft Tissue Sarcoma

Merkel Cell Carcinoma

Anti-Infective Agents

Gastrointestinal Agents

Antineoplastic Agents

Amino Acids

Antibodies

Antibodies, Monoclonal

Immunomodulating Agents

Poly I-C

Carboxymethylcellulose Sodium

Poly ICLC

Immunoglobulins

Antineoplastic Agents, Immunological

Immunoglobulins, Intravenous

Interferons

Laxatives

Cathartics

Antiviral Agents

Lysine

Patients receive recombinant Flt3 ligand IT on days 1-5 and undergo radiation therapy on day 8 or 9. Patients also receive agonistic anti-CD40 monoclonal antibody CDX-1140 IT and Poly-ICLC IT on day 9 or 10. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

Patients receive recombinant Flt3 ligand IT on days 1-5 and undergo radiation therapy on day 8 or 9. Patients also receive agonistic anti-CD40 monoclonal antibody IT and IV over 90 minutes and Poly-ICLC IT on day 9 or 10. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

Anti-CD40 Agonist Monoclonal Antibody CDX-1140

Radiation Therapy

Recombinant Flt3 Ligand

Kimberly Arieli

Fumito Ito, MD

This phase I trial evaluates the side effects of radio-immunotherapy (CDX-301, radiotherapy, CDX-1140 and Poly-ICLC) in treating patients with unresectable and measurable metastatic melanoma, cutaneous squamous cell carcinoma (SCC), Merkel cell carcinoma, high-grade bone and soft tissue sarcoma or HER2/neu(-) breast cancer. CDX-301 may induce cross-presenting dendritic cells, master regulators in the immune system. Radiation therapy uses high energy to kill tumor cells and release antigens that may be picked up, processed and presented by cross-presenting dendritic cells. CDX-1140 and Poly-ICLC may activate tumor antigen-loaded,cross-presenting dendritic cells, and generate tumor-specific T lymphocytes, a type of immune cells, that can search out and attack cancers. Giving immune modulators and radiation therapy may stimulate tumor cell death and activate the immune system.

PRIMARY OBJECTIVE:

I. To evaluate the safety profile of in situ immunomodulation with recombinant Flt3 ligand (CDX-301), radiotherapy, agonistic anti-CD40 monoclonal antibody CDX-1140, and Poly-ICLC in unresectable and metastatic melanoma, cutaneous squamous cell carcinoma, Merkel cell carcinoma, high-grade bone and soft tissue sarcoma or breast cancer patients with injectable palpable disease by determining the maximum tolerated dose (MTD) of CDX-1140 that has an acceptable adverse event profile.

SECONDARY OBJECTIVE:

I. To evaluate the immune signatures in the tumor microenvironment before and after in situ immunomodulation with CDX-301, radiotherapy, CDX-1140, and Poly-ICLC.

EXPLORATORY OBJECTIVES:

I. To record the overall response rate (ORR) (complete response \[CR\] and partial response \[PR\]) of injected as well as distant uninjected metastatic lesions in metastatic melanoma, cutaneous SCC, Merkel cell carcinoma, high-grade bone and soft tissue sarcoma or breast cancer patients with injectable palpable disease treated with in situ immunomodulation with CDX-301, radiotherapy, CDX-1140, and Poly-ICLC by immune-related Response Evaluation Criteria In Solid Tumors (irRECIST) response assessment, and compare intratumoral alone versus (vs.) intratumoral + intravenous administration of CDX-1140.

II. To record the overall survival (OS) and progression free survival (PFS) in unresectable and metastatic melanoma, cutaneous SCC, Merkel cell carcinoma, high-grade bone and soft tissue sarcoma or breast cancer patients with injectable palpable disease treated with in situ immunomodulation with CDX-301, radiotherapy, CDX-1140, and Poly-ICLC, and compare intratumoral alone vs. intratumoral + intravenous administration of CDX-1140.

III. Examine changes in the levels of T-cell subsets/myeloid derived suppressor cells (MDSC)/cytokines in peripheral blood (PB) of unresectable and metastatic melanoma, cutaneous SCC, Merkel cell carcinoma, high-grade bone and soft tissue sarcoma or breast cancer patients with injectable palpable disease treated with in situ immunomodulation with CDX-301, radiotherapy, CDX-1140, and Poly-ICLC.

OUTLINE:Cohort A will evaluate safety of intratumoral administration of CDX-1140 in combination with CDX-301, radiotherapy and Poly-ICLC. Once cohort A is finished, patients will be enrolled to cohort B to evaluate safety of intratumoral + intravenous administration of CDX-1140 in combination with CDX-301, radiotherapy and Poly-ICLC.

COHORT A: Patients receive recombinant Flt3 ligand intratumorally (IT) on days 1-5 and agonistic anti-CD40 monoclonal antibody CDX-1140 IT with Poly-ICLC IT on day 9 or 10. Patients also undergo radiation therapy on day 8 or 9. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

COHORT B: Patients receive recombinant Flt3 ligand IT on days 1-5 and agonistic anti-CD40 monoclonal antibody CDX-1140 IT and intravenously (IV) over 90 minutes with Poly-ICLC IT on day 9 or 10. Patients also undergo radiation therapy on day 8 or 9. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3-6 months for 2 years.

In Situ Immunomodulation With CDX-301, Radiation Therapy, CDX-1140 and Poly-ICLC in Patients w/ Unresectable and Metastatic Solid Tumors

A Phase I Study of In Situ Immunomodulation With CDX-301, Radiotherapy, CDX-1140, and Poly-ICLC in Patients With Unresectable and Metastatic Solid Tumors With Injectable Palpable Disease

ORR of distant uninjected metastatic lesions is defined as partial or complete response within 6 months of initiating combination therapy. Overall response will be summarized overall and by cohort using frequencies and relative frequencies, where the overall response rate will be estimated using a 90% confidence interval obtained by Jeffrey's prior method.

Will be summarized in the overall sample and by cohort using standard Kaplan-Meier methods; where estimates of the median will be obtained with 90% confidence intervals.

Will examine changes in the levels of PB biomarkers such as T-cell subsets/myeloid derived suppressor cells (MDSC)/cytokines in metastatic breast cancer patients treated with in situ immunomodulation with CDX-301, radiotherapy, CDX-1140, and poly-ICLC.

The dose limiting toxicity rate will be estimated by cohort and dose-level (if appropriate) using 90% confidence intervals obtained by Jeffrey's prior method.

Will examine changes in the immune biomarkers levels from baseline to end of treatment

Will examine changes in the levels of infiltrating CD4+ and CD8+ T cells and their proteomic, genomic and transcriptomic signatures in the tumor microenvironment. The immune biomarker levels are treated as continuous variables and will be summarized in the overall sample and within treatment-arm by time-point using the mean and standard error, and graphically using dot-plots.

Will examine changes in the levels of infiltrating myeloid cell subsets including dendritic cells (DCs), macrophages, and monocytes, and their proteomic, genomic and transcriptomic signatures in the tumor microenvironment. The immune biomarker levels are treated as continuous variables and will be summarized in the overall sample and within treatment-arm by time-point using the mean and standard error, and graphically using dot-plots.

Will examine changes in the levels of PD-L1 expression within both neoplastic and nonneoplastic stromal elements of the tumor microenvironment. The immune biomarker levels are treated as continuous variables and will be summarized in the overall sample and within treatment-arm by time-point using the mean and standard error, and graphically using dot-plots.

University of Southern California

Digestive System Diseases

Neoplasm Metastasis

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Hematinics

Herbal and Botanical

Liver Extracts

Cola

Michael A. Morse, MD

RATIONALE: Flt3L may stimulate a person's immune system and help kill tumor cells.

PURPOSE: Phase I trial to study the effectiveness of flt3L given to patients before undergoing surgery to remove metastases from colorectal cancer.

OBJECTIVES: I. Evaluate the safety and feasibility of administering flt3 ligand to patients with hepatic metastases from colorectal cancer prior to surgical resection.

OUTLINE: Patients receive flt3 ligand subcutaneously for 14 days followed by 14 days of rest. This course of therapy may be repeated for a total of 3 courses. Leukapheresis is performed on day 15 of the last course of Flt3 ligand. Patients undergo restaging and metastasis resection. Patients are followed every 3 months for the first year, every 6 months for the second year, and yearly thereafter.

PROJECTED ACCRUAL: This study will accrue 12 patients in 1 year.

Flt3L in Treating Patients With Metastatic Colorectal Cancer

Pilot Study of FLT3 Ligand Prior to Resection of Hepatic Metastases of Colorectal Cancer

Duke University

Immune System Diseases

Lymphoma

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Lymphoma, Non-Hodgkin

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoma, Mantle-Cell

Lymphoma, Follicular

Lymphoma, B-Cell, Marginal Zone

Lymphoma, Large B-Cell, Diffuse

Neutropenia

Lymphoma, B-Cell

Burkitt Lymphoma

Plasmablastic Lymphoma

Lymphoma, Large-Cell, Immunoblastic

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Agranulocytosis

Leukopenia

Cytopenia

Leukocyte Disorders

Lymphosarcoma

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Lymphocytic Leukemia

Mantle Cell Lymphoma

Follicular Lymphoma

B-cell Lymphoma

Marginal Zone Lymphoma

Diffuse Large B-Cell Lymphoma

Granulocytopenia

Lymphoma, Large-cell, Immunoblastic

Molgramostim

Sargramostim

Lenograstim

Epoetin Alfa

epoetin alfa

filgrastim

recombinant interleukin-3

sargramostim

in vitro-treated peripheral blood stem cell transplantation

Jane N. Winter, MD

RATIONALE: Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy used to kill cancer cells. Treating the peripheral stem cells in the laboratory may improve the effectiveness of the transplant.

PURPOSE: Phase I trial to study the effectiveness of peripheral stem cell transplantation in patients who have relapsed or refractory non-Hodgkin's lymphoma and who will be treated with high-dose chemotherapy.

OBJECTIVES:

* Determine the toxicity of ex vivo expanded peripheral blood mononuclear cells (EVE PBMNC) as a supplement to high-dose chemotherapy and conventional autograft in patients with relapsed or refractory non-Hodgkin's lymphoma.
* Compare the effect of EVE PBMNC on white blood cell, red blood cell, and platelet recovery in patients on this study vs historical controls, matched by protocol, disease status, and prior therapy.
* Determine the optimal duration of culture and time of harvest for the production of neutrophils in vivo.
* Determine the relationships between length of culture, immunophenotype, and clinical outcome.
* Determine the required numbers of white blood cell precursors for clinical efficacy.
* Assess the need for multiple transfusions of EVE PBMNC during the post-transplantation period.

OUTLINE: Autologous peripheral blood mononuclear cells (PBMNC) are harvested. Unselected PBMNC are cultured and expanded ex vivo in flt3 ligand, interleukin-3, filgrastim (G-CSF), sargramostim (GM-CSF), and epoetin alfa for 13 days. Expanded PBMNC are reinfused on day 0.

Patients are followed monthly for 1 year.

PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Biological Therapy in Treating Patients With Metastatic Melanoma or Metastatic Kidney Cancer	NCT00020540	Kidney Cancer Melanoma (Skin)	recombinant CD4... recombinant flt...	16 Years -	National Cancer Institute (NCI)
flt3L in Treating Patients With Acute Myeloid Leukemia	NCT00006223	Leukemia	recombinant flt...	18 Years -	National Cancer Institute (NCI)
Biological Therapy in Treating Patients With Metastatic Melanoma or Metastatic Kidney Cancer	NCT00020540	Kidney Cancer Melanoma (Skin)	recombinant CD4... recombinant flt...	16 Years -	National Cancer Institute (NCI)
In Situ Immunomodulation With CDX-301, Radiation Therapy, CDX-1140 and Poly-ICLC in Patients w/ Unresectable and Metastatic Solid Tumors	NCT04616248	Anatomic Stage ... Metastatic Brea... Prognostic Stag... Unresectable Br... Metastatic Mela... Unresectable Me... Cutaneous Squam... Merkel Cell Car... Soft Tissue Sar... Bone Sarcoma Sarcoma,Soft Ti... Sarcoma of Bone	Anti-CD40 Agoni... Poly ICLC Radiation Thera... Recombinant Flt...	18 Years -	University of Southern California
Biological Therapy in Treating Patients With Metastatic Melanoma or Metastatic Kidney Cancer	NCT00020540	Kidney Cancer Melanoma (Skin)	recombinant CD4... recombinant flt...	16 Years -	National Cancer Institute (NCI)
Flt3L in Treating Patients With Metastatic Colorectal Cancer	NCT00003431	Colorectal Canc... Metastatic Canc...	recombinant flt...	18 Years -	Duke University
Peripheral Stem Cell Transplantation to Prevent Neutropenia in Patients Receiving Chemotherapy for Relapsed or Refractory Non-Hodgkin's Lymphoma	NCT00005787	Lymphoma Neutropenia	epoetin alfa filgrastim recombinant flt... recombinant int... sargramostim in vitro-treate...	17 Years - 65 Years	Northwestern University

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