Astragalus for Symptomatic Alleviation in High-grade Lymphoma
NCT Number: NCT06510530
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE3
Conditions: High-grade Lymphoma
Interventions: DIETARY_SUPPLEMENT: Astragalus|DIETARY_SUPPLEMENT: Placebo
Sponsor: Bnai Zion Medical Center
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 60
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: QUADRUPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: PREVENTION
Start Date: 2024-08
Completion Date: 2032-08
Locations: Bnai Zion Medical Center, Haifa, 3339419, Israel

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.

Primary Outcome Measures: Quality-of-life, European Organization Research for Treatment of cancer core quality of life (EORTC-QLQ-C30) questionnaire summary score which is calculated from the mean of 13 of the 15 quality-of-life (QLQ-C30) scales of the questionnaire = (Physical Functioning+ Role Functioning+ Social Functioning+ Emotional Functioning+ Cognitive Functioning+ 100-Fatigue+ 100-Pain+ 100-Nausea_Vomiting+ 100-Dyspnoea+ 100-Sleeping Disturbances+ 100-Appetite Loss+ 100-Constipation+ 100-Diarrhoea)/13. Scores range from minimum 0 to maximum 100; a higher score represents a higher ("better") level of functioning, or a higher ("worse") level of symptoms., From baseline to end-of-treatment, up to 6 months
Secondary Outcome Measures: Symptoms, Measure Yourself Concerns and Wellbeing (MYCAW) questionnaire at end of treatment: two main concerns of the patient which are rated for severity using a simple numerical Likert scale 0-6 (0: not concerning at all; 6: very concerning)., From baseline to end-of-treatment, up to 6 months|Fatigue, European Organization Research for Treatment of cancer core quality of life (EORTC-QLQ-C30) questionnaire fatigue score. Scores range from minimum 0 to maximum 100; a higher score represents a higher ("worse") level of fatigue., From baseline to end-of-treatment, up to 6 months
Other Outcome Measures: Nausea and vomiting, European Organization Research for Treatment of cancer core quality of life (EORTC-QLQ-C30) questionnaire nausea\&vomiting score. Scores range from minimum 0 to maximum 100; a higher score represents a higher ("worse") level of nausea and vomiting., From baseline to end-of-treatment, up to 6 months|Cognitive function, European Organization Research for Treatment of cancer core quality of life (EORTC-QLQ-C30) questionnaire cognitive functioning score. Scores range from minimum 0 to maximum 100; a higher score represents a higher ("better") level of cognitive functioning., From baseline to end-of-treatment, up to 6 months|Severe neutropenia, Frequency of severe neutropenia episodes defined as absolute neutrophil count under 0.5x10\^9/L, 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)|Packed cells transfusion, Frequency of packed cells transfusion during the study treatment, Through the study treatment, up to 6 months|Use of Granulocyte colony stimulating factors (G-CSF), Frequency of G-CSF use during the study treatment, Through the study treatment, up to 6 months|Infections, Frequency of infections during the study treatment, Through the study treatment, up to 6 months|Hospitalizations, Frequency of hospitalizations during the study treatment, Through the study treatment, up to 6 months|Compliance to chemotherapy, Relative dose intensity (RDI) which is the ratio of delivered dose intensity (DDI) of chemotherapy with standard dose intensity (SDI) of chemotherapy = DDI/SDI, Through the study treatment, up to 6 months|Overall response rate (ORR), Percentage of patients who have a partial response or complete response to the treatment of lymphoma, Through the study treatment, up to 6 months|Complete response (CR) rate, Percentage of patients who have a complete response to the treatment of lymphoma, Through the study treatment, up to 6 months|Progression-free survival (PFS), The length of time during and after the treatment of lymphoma (first line) that patient lives and disease does not progress, Up to 2 years after end-of-study treatment: up to 2.5 years|Overall survival (OS), The length of time during and after the treatment of lymphoma (first line) that patient lives, Up to 2 years after end-of-study treatment: up to 2.5 years|Incidence of Treatment-Emergent Adverse Events, According to report of adverse events, severe adverse events, drug interactions, Through the study treatment, up to 6 months|Economic analysis, Calculation of quality-adjusted life years based on EuroQol-5 Dimension (EQ-5D) scale. The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient indicates health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. The EQ visual analogue scale (VAS) records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS can be used as a quantitative measure of health outcome that reflect the patient's own judgement., Through the study treatment, up to 6 months