Safety Trial of STING-dependent Activators and Stimulated Dendritic Cells for Aggressive Relapsed/Refractory Leukemias

NCT05321940 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 20200982
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this research is to investigate whether the combination of STING-dependent Adjuvants (STAVs) and dendritic cell (DC) vaccine therapies will increase the body's ability to fight aggressive relapsed or refractory leukemias.

Conditions

Refractory Leukemia; Relapsed Leukemia; Acute Myelogenous Leukemia; Acute Lymphoblastic Leukemia; Adult T-Cell Leukemia/Lymphoma

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Related Adverse events

  The incidence of treatment-limiting toxicities (TLTs) and treatment-related adverse events, including serious adverse events, in study participants will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, per physician discretion.

  Up to 12 months

Secondary Outcomes (7)

• Percentage of Participants Achieving Clinical Overall Response (OR)

  Up to 12 months

• Percentage of Participants Achieving Clinical Complete Response (CR)

  Up to 12 months

• Percentage of Participants with AML Achieving Clinical Complete Response rate with Incomplete Hematologic Recovery (CRi)

  Up to 12 months

• Percentage of Participants with Minimal Residual Disease (MRD)

  Up to 12 months

• Percentage of Participants Achieving Molecular Complete Response (MCR)

  Up to 12 months

Study Arms (1)

Combination STAVs and DC Vaccine Group

EXPERIMENTAL

Participants will receive STAV-loaded cells for a total of 5 doses on Days 3, 17, 31, 45 and 59. Participants will also receive up to 4 doses of dendritic vaccine on Days 10, 17, 24 and 31.

Biological: STING-Dependent Activators (STAVs) Loaded Autologous Leukemic Cells; Biological: Dendritic Cell Vaccine

Interventions

STING-Dependent Activators (STAVs) Loaded Autologous Leukemic Cells BIOLOGICAL

Autologous human ultraviolet (UV)-irradiated (dead) leukemia cells loaded with STAVs administered via intravenous injection. Each treatment will administer 5 ml via syringe.

Also known as: STING (Stimulator of Interferon Genes)-Dependent Activators, STAVs-Loaded Autologous Leukemic Cells, STING-dependent innate immune agonists

Combination STAVs and DC Vaccine Group

Dendritic Cell Vaccine BIOLOGICAL

15-20 Million mature dendritic cells per dose administered via intravenous injection.

Also known as: DC Vaccine

Combination STAVs and DC Vaccine Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically documented adult T-cell leukemia/lymphoma (ATLL), Cluster of Differentiation (CD)34+ acute myelogenous leukemia (AML), or acute lymphoblastic leukemia (B-cell or T-cell ALL). Eligible patients with ATLL must have leukemic involvement (See Appendix K for subtype classification).
• Must have evidence of persistent refractory disease or progression at the time of screening and documented presence of leukemic cells in peripheral blood by either morphology, histology, or flow cytometry.
• Must have failed standard induction and salvage therapies available AND be ineligible for allogeneic stem cell transplant ǂ as follows:
• For ATLL, must not have failed standard combination chemotherapy (i.e. doxorubicin or etoposide based regimen), salvage chemotherapy (i.e. ifosfamide + carboplatin + etoposide (ICE), dexamethasone, High-dose Cytarabine (Ara-C) and cisplatin (DHAP), or gemcitabine + oxaliplatin (GEMOX)), brentuximab vedotin if CD30+, interferon based therapy if acute or chronic type, and mogamulizumab provided patient is a suitable candidate for the above therapies ±.
• Relapsed/refractory (R/R) AML is defined as patients ≥ 18 years of age at the time of signing the informed consent form (ICF) who are not eligible to receive further intensive therapy and:
• Have failed to achieve a complete remission (CR) or morphologic complete remission with incomplete blood count recovery (CRi) after induction plus reinduction with intensive chemotherapy (e.g., anthracycline plus cytarabine or high-dose cytarabine containing regimens) if a suitable candidateǂ or 4 cycles of low-intensity therapy (i.e. azacytidine, or decitabine based regimens) (either 4 cycles of the same regimen or a combination of 2 different regimens) OR
• Have relapsed from CR or CRi from either intensive or low-intensity therapy. Subjects with second or multiple relapses are also eligible.
• For R/R ALL, the patient must have failed (relapsed or primary refractory) induction chemotherapy with consolidation if a suitable candidate± (i.e. ECOG 2993 or similar regimen). The patient should also have failed blinatumomab if CD19+ B-cell ALL, inotuzumab if CD22+ B-cell ALL, tyrosine kinase inhibitor if bcr-abl+, or salvage chemotherapy if available and if the patient is a suitable candidate± for these therapies.
• ± A suitable candidate is defined by a patient who has no contraindications to the available chemotherapy based on organ function, age, and overall health and performance status as determined by the treating physician.
• ǂ Transplant ineligible patients are defined as those not suitable for potentially curative allogeneic stem cell transplant based on lack of disease control or remission at the time of evaluation, inadequate organ function, age, and overall health and performance status as determined by the treating physician, or patient's refusal to undergo such treatment procedure.
• Adults (≥ 18 years of age) regardless of their gender and genetic background
• Karnofsky performance status (KPS) ≥ 50% or Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3. (see Appendix B for definitions).
• Must have adequate end organ and bone marrow function as defined below:
• Absolute neutrophil count (ANC)≥ 1,000 cells/mm3 (Exception: Unless cytopenias are secondary to leukemia disease).
• Platelets (PLT) ≥ 50,000 cells/mm3 (Exception: Unless cytopenias are secondary to leukemia).

You may not qualify if:

• Patients who have previously received allogeneic stem cell transplant are ineligible
• Patients receiving cytotoxic chemotherapy within 14 days or any other investigational biological agents within 7 days prior to initiation of study therapy.
• Any concomitant participation in other therapeutic trials.
• All patients will be required to be screened for Hepatitis B and C. Patients with active hepatitis B (HBsAg+ and Immunoglobulin M (IgM)+ for Hepatitis B core antigen) will not be eligible for trial enrollment. Those found to be Immunoglobulin G (IgG)+ for Hepatitis core antigen only may be eligible as long as they are receiving anti-Hepatitis B prophylactic therapy and liver function tests meet criteria listed under 4.1.10 above, and have no evidence of cirrhosis. The exact Hepatitis B therapy will be at the discretion of the infection disease specialist or investigator. Participants who are Hepatitis C antibody positive without a positive Hepatitis C RNA level, will be permitted to enroll in the study provided liver function tests meet criteria listed under 4.1.10 above, and have no evidence of cirrhosis on imaging.
• HIV infection.
• Active or latent syphilis.
• Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (CHF), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that are likely in the judgment of the Investigator(s) to interfere or limit compliance with study requirements/treatment.
• Patients with known central nervous system (CNS) involvement.
• Pregnant or breast-feeding women.
• Concurrent active malignancies, with the exception of in situ carcinoma of the cervix, non-metastatic, non- melanomatous skin cancer, or Kaposi's sarcoma not requiring systemic chemotherapy.
• Known New York Heart Association (NYHA) Class 3 or 4 heart disease as per Appendix C.
• Known history of cardiomyopathy with ejection fraction \< 45% (or lower limit of institutional normal value) or uncontrolled arrhythmia.
• Psychological, familial, sociological or geographical conditions likely in the judgment of the Investigator(s) to interfere or limit compliance with study requirements/treatment
• Known active deep venous thrombosis (DVT) or pulmonary embolism

Sponsors & Collaborators

• Juan C. Ramos, MD: lead

MeSH Terms

Conditions

Leukemia; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Interventions

lentiviral minigene vaccine of COVID-19 coronavirus

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Juan C Ramos, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Clinical

Study Record Dates

• First Submitted: April 1, 2022
• First Posted: April 11, 2022
• Study Start: November 30, 2023
• Primary Completion: November 30, 2025
• Study Completion (Estimated): November 30, 2026
• Last Updated: December 4, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share