Clinical trial NCT06510530: Astragalus for Symptomatic Alleviation in High-grade Lymphoma
Official title: Efficacy and Safety of Astragalus for Symptomatic Alleviation in Patients With High-grade Lymphoma Treated With Chemotherapy: a Double-blind Randomized Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: High-grade Lymphoma
Lead sponsor: Bnai Zion Medical Center
Sponsor class: OTHER_GOV
First posted: 2024-07-19
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Lymphoma is a malignant disease of the lymph nodes. There are different types of lymphoma: when some of the lymphomas are indolent and require only follow-up, in cases of aggressive lymphoma or indolent lymphoma with a burden of disease, treatment is necessary, which usually includes chemotherapy with or without biological drugs. These drugs often cause significant damage to the quality of life, various symptoms including exhaustion, neuropathic pain, nausea/vomiting, cognitive decline, as well as a drop in blood counts with serious life-threatening infections that cause a delay in the treatment date that may affect the prognosis.

Drug treatments for symptomatic relief and improvement in quality of life in patients with lymphoma are missing, with only a partial effect and involving side effects.

Astragalus (scientific name: Astragalus membranaceus, common name: Huang Qi) is a perennial flowering plant common in China with a long history of use in traditional Chinese medicine. It is given in various forms of root in combination with other herbs, medicinal soups and as tablets, capsules, solutions, ointments for local use, or subcutaneous or intravenous injection. In patients with oncological diseases, a systematic review (4 trials on a total of 342 patients) showed an improvement in nausea and vomiting as well as in the immune system in patients with colon cancer who received Chemotherapy. A meta-analysis of 27 studies on 1,843 patients with colon cancer also demonstrated a reduction in chemotherapy-induced nausea in patients who received a combination of astragalus with chemotherapy compared to chemotherapy alone. In another meta-analysis that included 45 trials on 3,236 patients with liver cancer, an improvement in 12-month survival was reported with products containing astragalus. In a randomized study of 136 patients with lung cancer, three treatment cycles with astragalus by injection in combination with chemotherapy (vinorelbine and cisplatin) resulted in a significant improvement in quality of life compared to the control group that received chemotherapy alone. Similar results found in 23 patients with metastatic malignancy receiving astragalus by injection in combination with chemotherapy. In addition, a study on 90 patients with advanced cancer showed an improvement in fatigue in patients who received astragalus. Also, a pilot study on 60 patients with breast cancer showed that intravenous administration of astragalus improved blood counts in patients who received it in combination with chemotherapy compared to chemotherapy alone. In patients with hematological malignancies, a study was conducted on 498 patients with acute myeloid leukemia and showed that the use of astragalus or plants containing astragalus was associated with improved survival compared to patients who did not receive it. In the context of lymphoma, a pharmacological study in vivo on animals with lymphoma showed that a combination of an astragalus-containing formula with adriamycin-type chemotherapy improved the effect of adriamycin for the treatment of B-cell lymphoma. Another study in patients who had completed conventional chemotherapy with Rituximab Cyclophosphamide Adriamycine Vincristine Prednisone (R-CHOP) for diffuse large B-cell lymphoma showed that administration of a formula containing astragalus improved immune function and blood counts. Finally, a randomized placebo-controlled study showed that giving a formula containing astragalus to patients under R-CHOP chemo-immunotherapy as first line for diffuse large B cell lymphoma high risk significantly reduced the appearance of side effects from the treatment and improved response to the treatment chemotherapy compared to the control group.

Side effects attributed to astragalus include fatigue, weakness, headaches and hypotension, but in the cited studies and meta-analyses, no increase in the rate of side effects was found in the groups of patients who received this plant compared to the control groups, and no safety problems were described in the use of astragalus in combination with chemotherapy.

In light of the multitude of symptoms that affect the quality of life and adherence to treatment in patients with lymphoma receiving chemotherapy, and in light of the encouraging findings in the literature about symptomatic improvement as a result of combining astragalus during chemotherapy in various malignancies, the investigators aim to examine the effectiveness and safety of astragalus during the treatment of patients with high-grade lymphoma on symptomatic relief and adherence to chemotherapy in a randomized, double-blind, placebo-controlled study.


Eligibility criteria: Inclusion Criteria:

* Age over 18
* Diagnosis of high-grade lymphoma
* Need to start treatment for lymphoma that includes chemotherapy as first line
* Possibility to answer questionnaires once a month
* Signing an informed consent form

Exclusion Criteria:

* Taking up to a week before the randomization a drug with the potential for an interaction of major clinical significance with Astragalus according to a professional database
* Administration of chemotherapy in the past
* Significant disturbance in liver enzymes: Aspartate transaminase and/or alanine transaminase above 5 times the upper limit of normal
* Significant renal dysfunction: glomerular filtration rate under 30 ml/min according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
* Active autoimmune disease
* Pregnancy or breastfeeding
* Active participation in another interventional study
* Psychiatric disorder with impaired cognitive qualifications

Primary outcomes:
measure: Quality-of-life
timeFrame: From baseline to end-of-treatment, up to 6 months
Secondary outcomes:
measure: Symptoms
timeFrame: From baseline to end-of-treatment, up to 6 months
measure: Fatigue
timeFrame: From baseline to end-of-treatment, up to 6 months
Other outcomes:
measure: Nausea and vomiting
timeFrame: From baseline to end-of-treatment, up to 6 months
measure: Cognitive function
timeFrame: From baseline to end-of-treatment, up to 6 months
measure: Severe neutropenia
timeFrame: Evaluated at day 10-13 of each cycle (each cycle is 14-28 days depending on chemotherapy protocol) during the study treatment (up to 6 months)
measure: Packed cells transfusion
timeFrame: Through the study treatment, up to 6 months
measure: Use of Granulocyte colony stimulating factors (G-CSF)
timeFrame: Through the study treatment, up to 6 months
measure: Infections
timeFrame: Through the study treatment, up to 6 months
measure: Hospitalizations
timeFrame: Through the study treatment, up to 6 months
measure: Compliance to chemotherapy
timeFrame: Through the study treatment, up to 6 months
measure: Overall response rate (ORR)
timeFrame: Through the study treatment, up to 6 months
measure: Complete response (CR) rate
timeFrame: Through the study treatment, up to 6 months
measure: Progression-free survival (PFS)
timeFrame: Up to 2 years after end-of-study treatment: up to 2.5 years
measure: Overall survival (OS)
timeFrame: Up to 2 years after end-of-study treatment: up to 2.5 years
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: Through the study treatment, up to 6 months
measure: Economic analysis
timeFrame: Through the study treatment, up to 6 months
Locations:
city: Haifa
country: Israel
facility: Bnai Zion Medical Center
Study officials:
affiliation: Bnai Zion Medical Center
name: Ilana Levy Yurkovski, MD
role: PRINCIPAL_INVESTIGATOR
References: