Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Symptoms and General Pathology

Rare Diseases

Sarcoma

Respiratory Aspiration

Rhabdomyosarcoma

Myosarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Soft Tissue Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Anti-Infective Agents

Irinotecan

Etoposide

Vinorelbine

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Vincristine

Ifosfamide

Dactinomycin

Etoposide phosphate

Isophosphamide mustard

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Tubulin Modulators

Antimitotic Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Participants will receive 42 weeks of conventional doses of vinorelbine, actinomycin D and cyclophosphamide

Participants will receive conventional doses of Vincristine/Actinomycin D/Cyclophosphamide (VAC) until complete response (CR) for 12-42 weeks and then switch to up to 2 years of vinorelbine/oral cyclophoshamide

Therapy with VAC that starts and stops based on response, adaptive timing of therapy, with a prolonged time to progression rather than complete remission goal

Participants will receive a chemotherapy combination based on published trials. An example would be 42 weeks of VAC but may also include irinotecan, doxorubicin, ifosfamide, etoposide.

IV push over 1 minute with dosing ranging from 0.24mg up to 1.5mg

IV over 60 minutes with dosing ranging from 220mg to 1200mg

IV push over 6-10 minutes with dosing ranging from 4mg-25mg

Actinomycin D should not be given with radiation. Will be administered through IV over 3-5 minutes with dosing ranging from 0.025mg-0.045mg

Actinomycin D

Based on Body Surface Area (BSA) round to nearest 25mg

Cyclophosphamide Pill

Jessica Crimella, BSN, RN

Stella Valavanis, MPH

Jennifer Madison

Bridget Tate

Elizabeth Alva, MD

Sarah Miller

Emily Blauel-Bocko, MD

Robin Arens

Michael Scott Isakoff, MD

Ashley P Bayne

Joanne P Lagmay, MD

Eva Pavicic

Aditi Dhir, MD

Brittani Froug

Emily Riffle

Jonathan Metts, MD

Jessica R Crimella, BSN, RN

Rebecca Zylber

Alice Lee, MD

Stephanie Guilford

Ajay Gupta, MD

Juanita Cuffee

Patrick Thompson, MD

Devika Srivastava

Abigail Moore

Javier Oesterheld, MD

Lars Wagner, MD

Melissa Serna

Matteo Trucco, MD

Hannah Johns

Bhuvana Setty, MD

Joshua Blatner

Scott Borinstein, MD

Nupur Goel

Patrick Leavey, MD

Latasha Williams

Jonathan Gill, MD

Jessica Jensen

Michelle Grant

Matthew Dietz, MD

This clinical trial will evaluate 4 different strategies of chemotherapy schedules in newly diagnosed participants with metastatic Fusion Positive (alveolar) Rhabdomyosarcoma. The participant and their physician will choose from: Arm A) a first strike therapy, Arm B) a first strike-second strike (maintenance) therapy, Arm C) an adaptively timed therapy, and Arm D) conventional chemotherapy.

Evolutionary Therapy for Rhabdomyosarcoma

Evolutionary Inspired Therapy for Newly Diagnosed, Metastatic, Fusion Positive Rhabdomyosarcoma

Participants who choose the first strike treatment will have event free survival assessed at 3 years after initiating treatment. Event free survival is defined as time from treatment initiation to event which includes (1) any recurrence (local or regional, or distant) and (2) death due to any cause.

Participants who choose the second strike treatment will have event free survival assessed at 3 years after initiating treatment. Event free survival is defined as time from treatment initiation to event which includes (1) any recurrence (local or regional, or distant) and (2) death due to any cause

Participants who choose the adaptive therapy will have event free survival assessed at 3 years after initiating treatment. Event free survival is defined as time from treatment initiation to event which includes (1) progression that does not respond to additional VAC dosing and (2) death due to any cause

The time to event endpoint of overall survival is defined as the duration of time from diagnosis to death or last follow-up, where event would be death from any cause

Number of participants with treatment-related adverse events of a certain grade or higher and hematological/biochemical toxicities based on laboratory measurements as assessed by CTCAE v5.0

National Pediatric Cancer Foundation

H. Lee Moffitt Cancer Center and Research Institute

Vaccines

Immunomodulating Agents

Imiquimod

Adjuvants, Immunologic

Interferons

TAPA-Pulsed DC Vaccine Cyclophosphamide Pill Imiquimod Topical Cream

Subjects will given the vaccine which contains 1 x 10\^7 TAPA-pulsed dendritic cells and is administered ID. A total of three (3) cycles therapy will be administered weekly.

TAPA-pulsed DC vaccine

Subjects will be given low-dose cyclophosphamide by mouth for 5 days starting 5 to 7 days prior to the vaccine cycle.

Topical Imiquimod Cream will be applied after vaccination.

Imiquimod Topical Cream

Anthony Tolcher, MD

Patients diagnosed with progressive and/or refractory solid malignancies, who have failed conventional therapy, and have no available, potentially curative therapeutic options, will be candidates for this Phase I/II study. Following confirmation of disease progression and/or refractoriness, eligible patients who agree to participate and sign an informed consent form will have their tumor cells/tissues and/or blood analyzed for the expression of a specific panel of Tumor Associated Peptide Antigens (TAPAs), including Sp17, ropporin, AKAP-4, PTTG1, Span-xb, Her-2/neu, HM1.24, NY-ESO-1 and MAGE-1.

For patients whose tumors express one (1) or more of these TAPAs (Sp17, ropporin, AKAP-4, PTTG1, Span-xb, Her-2/neu, HM1.24, NY-ESO-1 and MAGE-1), whole blood will be obtained by phlebotomy and/or leukapheresis performed for generation of autologous DCs. Patient's DCs will be generated in Kiromic's Cell Processing GMP facility, according to established Standard Operating Procedures, and activated by pulsing/loading them with the TAPA(s) relevant for each particular patient. Patients will receive five (5) days of low-dose cyclophosphamide 5 to 7 days prior to each vaccination with TAPA-pulsed DCs to decrease Treg activity. Patients will also receive a single dose of topical Imiquimod cream after each vaccination. TAPA-pulsed DCs will be administered at a fixed dose of up to 1 X 107 DCs. DC vaccination schedule will be weekly via intradermal (ID) injections for a total of 3 vaccinations. Topical Imiquimod cream will also be administered once after the vaccination. Patients will be followed on a weekly basis (or more frequently if required) to evaluate treatment-related toxicity. Immune efficacy and anti-tumor responses will be evaluated per protocol specifications. Continuation and stopping rules for the study will be defined based on toxicity/tolerability (Phase I) and immune efficacy (Phase II).

Cyclophosphamide, TAPA-Pulsed Dendritic Cell Therapy and Imiquimod in Progressive and/or Refractory Solid Malignancies

Phase I/II Study of Low-Dose Cyclophosphamide, Tumor Associated Peptide Antigen-Pulsed Dendritic Cell Therapy and Imiquimod, in Patients With Progressive and/or Refractory Solid Malignancies

Grade, causality, start/stop dates (duration), resolutions for adverse events will be monitored and recorded.

The response of T-cells present in the peripheral blood mononuclear cells (PBMCs) population to the peptides used to pulse a patient's dendritic cell vaccine is evaluated by measuring the expression of Th1/CTL-type cytokines (IFN-γ and/or TNF-α and/or IL-17) by a standard ELI-Spot assay using 500,000 PBMCs per experimental replicate and a minimum of 3 experimental replicates for each stimulation. The results are expressed as the average number of spots obtained from the stimulation of 500,000 PBMCs

DTH skin test will be performed on subject's forearm or within 5 cm from the site of prior DC vaccination, if possible

Kiromic BioPharma Inc.

TAPA-Pulsed DC Vaccine Cyclophosphamide Pill Imiquimod Topical Cream

TAPA-pulsed DC vaccine: Subjects will given the vaccine which contains 1 x 10\^7 TAPA-pulsed dendritic cells and is administered ID. A total of three (3) cycles therapy will be administered weekly.

Cyclophosphamide Pill: Subjects will be given low-dose cyclophosphamide by mouth for 5 days starting 5 to 7 days prior to the vaccine cycle.

Imiquimod Topical Cream: Topical Imiquimod Cream will be applied after vaccination.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Evolutionary Therapy for Rhabdomyosarcoma	NCT04388839	Rhabdomyosarcom...	Vincristine Cyclophosphamid... Vinorelbine Actinomycin D Cyclophosphamid...	-	H. Lee Moffitt Cancer Center and Research Institute
Cyclophosphamide, TAPA-Pulsed Dendritic Cell Therapy and Imiquimod in Progressive and/or Refractory Solid Malignancies	NCT02224599	Progressive Sol... Refractory Soli... Cancer	TAPA-pulsed DC ... Cyclophosphamid... Imiquimod Topic...	-	Kiromic BioPharma Inc.

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