Plasmodium Immunotherapy for Advanced Malignant Solid Tumors

NCT ID: NCT04165590

Last Updated: 2024-02-20

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

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-10-24

Study Completion Date

2026-10-31

Brief Summary

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The purpose of this study is: 1) to evaluate the effectiveness and extended safety of the Plasmodium immunotherapy for the advanced malignant solid tumors. 2) To explore the safe and effective course of the Plasmodium immunotherapy for the advanced malignant solid tumors. 3) To explore the possible indications of Plasmodium immunotherapy for advanced malignant solid tumors.

The treatment will last 5-10 weeks from the day of successful infection and will be terminated by antimalarial drugs.

Detailed Description

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This study is planed to enroll 60 patients. Each patient will be vaccinated with 2 ml of P. vivax-infected red blood cells, containing approximately 0.1-1.0 × 10\^7 Plasmodium parasites. The treatment will last for 5-10 weeks from the day of successful infection. During the period of Plasmodium immunotherapy, doctor will use artesunate to control the P. vivax erythrocyte infection rate at a low level, so as to prevent the severe adverse event. After 5-10 weeks, parasitemia will be terminated by antimalarial drugs for ending the treatment of Plasmodium immunotherapy (the immunological treatment effect may persist after the termination of Plasmodium infection). After the treatment, patients will be followed up for 2 years.

Conditions

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Advanced Malignant Solid Tumor

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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Blood-stage infection of P.vivax

This is a single arm study that is planed to enroll 60 patients with advanced malignant solid tumor and each patient will be vaccinated with P.vivax-infected red blood cells containing approximately 0.1-1.0 × 10\^7 Plasmodium parasites. And successful infection will be indicated by microscopic observation of parasitemia in peripheral blood samples. The treatment will last 5-10 weeks from the day of successful infection and will be terminated by antimalarial drugs.

Group Type EXPERIMENTAL

Plasmodium immunotherapy

Intervention Type OTHER

The patient will be vaccinated with P. vivax-infected red blood cells containing approximately 0.1-1.0 × 10\^7 Plasmodium parasites.

Interventions

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Plasmodium immunotherapy

The patient will be vaccinated with P. vivax-infected red blood cells containing approximately 0.1-1.0 × 10\^7 Plasmodium parasites.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. Aged 18-70 years male or female.
2. Patients with advanced maligant solid tumors in lung, liver, prostate, ovary, brain, thyroid and colorectum, etc.
3. Patients with primary central nervous system (CNS) tumor or brain metastases from solid tumors, comply with the following standards can participate in this study: Up to the clinical trial screening period, the imageological examination provides progression-free evidence for at least 3 months, blood brain barrier has not been damaged or is already recovered from the former treatment (surgery or radiotherapy) injury, without intracranial hemorrhage or myelorrhagia history, without metastases to the brain stem, midbrain, pons, medulla oblongata or eye subsidiary organs within 10 mm area (the optic nerve and optic chiasma).
4. The patients have measurable tumors based on the criterion of RECIST1.1.
5. Tumor classification should be determined by histopathology and pathological report should be provided. If tumor tissue is available, before participating in the trail, the research center need to obtain the paraffin blocks or at least 6 unstained sections of the tumor tissue and the relevant pathological reports. If the above tumor tissue samples are not available, samples of any kind (such as fine needle aspiration biopsy samples, cell mass samples (such as pleural, peritoneal effusion samples and lavage samples) are acceptable. If tumor tissue is not available, patients are still eligible for the study.
6. For the patients who previously received one or more of the following therapies, the interval time of the termination of chemotherapy (including interventional chemotherapy) or radiotherapy is at least 28 days for patients who had received chemotherapy or radiotherapy; at least 5 half-life time for patients who had received targeted drug therapy (the half-life of targeted drug is according to the drug instructions).
7. ECGO score is 0 to 2, and euphagia.
8. Expected survival ≥ 3 months.
9. WBC≥3× 10\^9/L, PLT ≥ 100× 10\^9/L, HGB ≥ 100 g/L, and albumin ≥ 30 g/L, no significant morphological abnormalities of red blood cells, or anemia (iron deficiency anemia, autoimmune hemolytic anemia, thalassemia, etc.).
10. Patients with gastrointestinal bleeding, hemoptysis or other chronic bleeding symptoms were cured before enrollment.
11. Patients with no severe dysfunction of cardiopulmonary, liver and kidney function (child-push grading of liver function A or B, Cr≤ 1.5 x ULN).
12. Patient will be able to understand and sign informed consent.
13. According to the researcher's judgment, the patient's compliance could meet the needs of follow-up.

Exclusion Criteria

1. Nasopharyngeal cancer, head and neck tumors.
2. HPV positive patients with advanced malignant solid tumors in cervical, anal, vulvar, vaginal and penile.
3. Pancreatic cancer patients.
4. Small cell lung cancer patients.
5. Patients with severe hemoglobin disease or severe G6PD deficiency.
6. Patients with splenectomy or splenomegaly.
7. Patients with drug addiction or alcohol dependence.
8. Have not yet been washed out from the previous therapeutic effects, except the following: the bisphosphonates used for bone metastasis or osteoporosis.
9. Uncontrolled pleural effusion, pericardial effusion or ascites.
10. Tumor-related pain that are uncontrollable.
11. Active malignant tumor metastasis of CNS (progression or controlling the symptoms with anticonvulsants or corticosteroids ).
12. Patients with significant immunodeficiency detection ( CD4+T cell absolute count \<200 /ul)
13. With the following diseases or conditions: serious or uncontrolled systemic disease or any unstable systemic diseases (including but not limited to active infection, grade three hypertension, unstable angina, congestive heart failure, class III or IV heart disease, severe arrhythmia, liver and kidney dysfunction or metabolic disease), a clear history of neurological or psychiatric disorders, etc.
14. According to the principal investigator's judgment, any other diseases, metabolic disorders, abnormal results of clinical laboratory tests or physical examination, the diseases that leading to usage of the prohibited drugs, influencing the results reliability, putting patients in high risk.
15. Have undergone major surgery within 4 weeks of the screening period, or plan to undergo major surgery during the study period, PICC catheter and central venous catheter implantation are excluded.
16. Received any antineoplastic drugs, immune cells, antibodies, or vaccines within five drug half-life (not sure the half-life, will be subject to two weeks) during the screening period.
17. Patients who have previously received allogeneic bone marrow transplantation or solid organ transplantation.
18. Receiving any other anti-tumor treatment at the same time.
19. Lung function is seriously damaged, the MNW \<39% or can't get out of bed, still feel short of breath when resting.
20. Rough cough, dyspnea, without normal diet or difficult to cooperate.
21. Poor body condition, the researchers assess that the patients can't tolerate the Plasmodium immunotherapy.
22. Pregnant or lactating women.
23. Patients that are unable to comply with the research and follow-up procedure.
24. Any case that the researchers believe that the patient does not suit for this clinical study.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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CAS Lamvac Biotech Co., Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Hou Jianghou, Ph.D

Role: STUDY_DIRECTOR

Yunnan Kungang Hospital

Locations

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Yunnan Kungang Hospital

Kunming, Yunnan, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Qin Li, Ph.D

Role: CONTACT

0086-18802043960

Huang Qiumei, M.D

Role: CONTACT

0086-20-82258809

Facility Contacts

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Hou Jianghou, Ph.D

Role: primary

86+15116919815

Xu Jinsong, M.D

Role: backup

86+13888866278

References

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Chen L, He Z, Qin L, Li Q, Shi X, Zhao S, Chen L, Zhong N, Chen X. Antitumor effect of malaria parasite infection in a murine Lewis lung cancer model through induction of innate and adaptive immunity. PLoS One. 2011;6(9):e24407. doi: 10.1371/journal.pone.0024407. Epub 2011 Sep 9.

Reference Type RESULT
PMID: 21931708 (View on PubMed)

Qin L, Chen C, Chen L, Xue R, Ou-Yang M, Zhou C, Zhao S, He Z, Xia Y, He J, Liu P, Zhong N, Chen X. Worldwide malaria incidence and cancer mortality are inversely associated. Infect Agent Cancer. 2017 Feb 14;12:14. doi: 10.1186/s13027-017-0117-x. eCollection 2017.

Reference Type RESULT
PMID: 28228842 (View on PubMed)

Yang Y, Liu Q, Lu J, Adah D, Yu S, Zhao S, Yao Y, Qin L, Qin L, Chen X. Exosomes from Plasmodium-infected hosts inhibit tumor angiogenesis in a murine Lewis lung cancer model. Oncogenesis. 2017 Jun 26;6(6):e351. doi: 10.1038/oncsis.2017.52.

Reference Type RESULT
PMID: 28650446 (View on PubMed)

Liu Q, Yang Y, Tan X, Tao Z, Adah D, Yu S, Lu J, Zhao S, Qin L, Qin L, Chen X. Plasmodium parasite as an effective hepatocellular carcinoma antigen glypican-3 delivery vector. Oncotarget. 2017 Apr 11;8(15):24785-24796. doi: 10.18632/oncotarget.15806.

Reference Type RESULT
PMID: 28445973 (View on PubMed)

Adah D, Yang Y, Liu Q, Gadidasu K, Tao Z, Yu S, Dai L, Li X, Zhao S, Qin L, Qin L, Chen X. Plasmodium infection inhibits the expansion and activation of MDSCs and Tregs in the tumor microenvironment in a murine Lewis lung cancer model. Cell Commun Signal. 2019 Apr 12;17(1):32. doi: 10.1186/s12964-019-0342-6.

Reference Type RESULT
PMID: 30979375 (View on PubMed)

Related Links

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5307699/

Free full text.This article has been cited by other articles in PMC.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5519199/

Free full text.This article has been cited by other articles in PMC.

Other Identifiers

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KGYY-002

Identifier Type: -

Identifier Source: org_study_id

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