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

NCT ID: NCT05321940

Last Updated: 2023-12-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE1

Study Classification

INTERVENTIONAL

Study Start Date

2023-11-30

Study Completion Date

2026-11-30

Brief Summary

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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.

Detailed Description

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Conditions

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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Combination STAVs and DC Vaccine Group

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.

Group Type EXPERIMENTAL

STING-Dependent Activators (STAVs) Loaded Autologous Leukemic Cells

Intervention Type BIOLOGICAL

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

Dendritic Cell Vaccine

Intervention Type BIOLOGICAL

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

Interventions

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STING-Dependent Activators (STAVs) Loaded Autologous Leukemic Cells

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

Intervention Type BIOLOGICAL

Dendritic Cell Vaccine

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

Intervention Type BIOLOGICAL

Other Intervention Names

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STING (Stimulator of Interferon Genes)-Dependent Activators STAVs-Loaded Autologous Leukemic Cells STING-dependent innate immune agonists DC Vaccine

Eligibility Criteria

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Inclusion Criteria

1. 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).
2. 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.
3. 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.
4. Adults (≥ 18 years of age) regardless of their gender and genetic background
5. Karnofsky performance status (KPS) ≥ 50% or Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3. (see Appendix B for definitions).
6. Must have adequate end organ and bone marrow function as defined below:
7. Absolute neutrophil count (ANC)≥ 1,000 cells/mm3 (Exception: Unless cytopenias are secondary to leukemia disease).
8. Platelets (PLT) ≥ 50,000 cells/mm3 (Exception: Unless cytopenias are secondary to leukemia).
9. Hepatic function: transaminase ≤ 2.5 x the institutional upper limit of normal, total bilirubin ≤ 1.5 x institutional upper limit of normal, (Exception: Unless secondary to hepatic infiltration with leukemia).
10. Females of childbearing potential (CBP) must have a negative pregnancy test within one week of enrollment. Women should avoid pregnancy while receiving study treatment. Males and females must agree to use adequate methods of birth control during participation in this trial and for 3 months after completing therapy
11. Patients receiving erythropoietin or granulocyte colony-stimulating factor (G-CSF) from baseline are eligible.
12. Ability to understand and willingness to sign a written informed consent document. Written consent by patient or legal guardian on an institutional review board (IRB)-approved informed consent form prior to any study-specific evaluation. Subject or legal guardian must be capable of understanding the investigational nature, potential risks and benefits of the study and able to provide valid informed consent.

Exclusion Criteria

1. Patients who have previously received allogeneic stem cell transplant are ineligible
2. Patients receiving cytotoxic chemotherapy within 14 days or any other investigational biological agents within 7 days prior to initiation of study therapy.
3. Any concomitant participation in other therapeutic trials.
4. 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.
5. HIV infection.
6. Active or latent syphilis.
7. 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.
8. Patients with known central nervous system (CNS) involvement.
9. Pregnant or breast-feeding women.
10. 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.
11. Known New York Heart Association (NYHA) Class 3 or 4 heart disease as per Appendix C.
12. Known history of cardiomyopathy with ejection fraction \< 45% (or lower limit of institutional normal value) or uncontrolled arrhythmia.
13. Psychological, familial, sociological or geographical conditions likely in the judgment of the Investigator(s) to interfere or limit compliance with study requirements/treatment
14. Known active deep venous thrombosis (DVT) or pulmonary embolism
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Juan C. Ramos, MD

OTHER

Sponsor Role lead

Responsible Party

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Juan C. Ramos, MD

Professor of Clinical

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Juan C Ramos, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Countries

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United States

Other Identifiers

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20200982

Identifier Type: -

Identifier Source: org_study_id