Mistletoe Immunotherapy for Osteosarcoma

Recruiting at 1 trial location

Overseen By Laura Goode, MS, RN, PCNS-BC

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Hackensack Meridian Health

Must not be taking: Immunostimulants, Immunosuppressives

Disqualifiers: Other cancers, Active infection, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 52 weeks

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called Iscador® P, a type of immunotherapy, to determine its effectiveness for people with osteosarcoma, a type of bone cancer, who have experienced cancer spread to their lungs. The goal is to assess whether this treatment can prevent cancer recurrence after surgery has removed all visible tumors. Participants will receive injections three times a week for up to a year. This trial suits those who have had lung cancer from osteosarcoma at least once, have undergone surgery to remove it, and can manage regular injections. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications, but you cannot receive any additional chemotherapy, immunotherapy, or immunostimulant or immunosuppressive drugs while on the study.

Is there any evidence suggesting that Iscador® P is likely to be safe for humans?

Research shows that Iscador® P, a mistletoe extract, has been approved in countries like Sweden and Germany for treating solid tumors, indicating its safety for humans. In past studies, mistletoe extracts have treated cancer patients with some success, and patients have generally tolerated the treatment well.

Researchers administer Iscador® P in carefully controlled doses to minimize side effects. Treatment begins with a low dose, gradually increasing to find the optimal dose for each person. This approach helps avoid serious side effects and ensures safety.

While researchers continue to test Iscador® P for this specific use, its approval for other conditions in several countries offers reassurance about its safety. Overall, past data shows that most patients tolerate the treatment well. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for osteosarcoma?

Unlike the standard treatments for osteosarcoma, which often involve surgery, chemotherapy, and radiation, Iscador® P is derived from mistletoe extract and focuses on boosting the body's immune response. This treatment is unique because it uses a strategy of gradually increasing doses to find the optimal level for each patient, aiming to enhance the immune system's ability to fight cancer cells while minimizing toxicity. Researchers are excited about Iscador® P because it represents a potential new approach to treating osteosarcoma by harnessing the body's natural defenses, offering hope for improved outcomes with fewer side effects.

What evidence suggests that Iscador® P might be an effective treatment for osteosarcoma?

Research has shown that mistletoe therapy, such as Iscador® P, which participants in this trial will receive, can benefit people with osteosarcoma, a type of bone cancer. Studies have found that mistletoe extracts can help patients remain disease-free longer after a second cancer relapse. In some cases, it also enhances overall quality of life. This treatment involves injecting a natural extract from the mistletoe plant and is approved in several countries for treating solid tumors. While the results are promising, the treatment's effectiveness can vary from person to person. ^{1 2 3 4 6}

Who Is on the Research Team?

Katharine Offer

Principal Investigator

Hackensack Meridian Health

Karen Moody, MD

Principal Investigator

MD Anderson

Are You a Good Fit for This Trial?

This trial is for osteosarcoma patients aged 8-30 who've had lung metastases surgically removed and are in at least their second complete remission. They must be able to handle subcutaneous injections, have a certain level of physical ability, adequate organ function, no active infections or other cancers, not pregnant or breastfeeding, and agree to use contraception.

Inclusion Criteria

Female patients of childbearing potential must have a negative serum blood pregnancy test during screening and a negative urine pregnancy test within 3 days prior to receiving the first dose of study drug

Life expectancy of > two months

Side effects from my last cancer treatment have mostly gone away.

Exclusion Criteria

I had radiation therapy within the last two weeks.

Pregnancy or breastfeeding for female patients

I have recently undergone chemotherapy or immunotherapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Iscador® P subcutaneously 3 times per week with escalating doses over 52 weeks

52 weeks

3 visits per week (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Iscador® P

Trial Overview

The study tests Iscador® P immunotherapy on patients with recurrent osteogenic sarcoma after pulmonary metastases resection. It's a phase II trial where participants receive the manufacturer-recommended maximum tolerated dose (MTD) of Iscador® P with regular CT scans to monitor relapse.

How Is the Trial Designed?

Group I: Treatment Arm - Iscador*P Experimental Treatment 1 Intervention

Each Iscador® P therapy begins with a dose finding phase related to the drug' immunogenicity. In this phase, gradually increasing doses are used to determine the optimum individual dose response of the patient and to prevent excessive toxicity. The Iscador® P will be administered three times per week by subcutaneous injections (M,W,F) into the subcutaneous tissue of the thigh or abdomen. Treatment is administered according to a series of escalating doses that are given each of the three days in a week for 7 doses. There are 3 different series (Series 0, 1, and 2) and there are 7 dose vials in each series. Once the patient has reached their maximum tolerated dosing series, that series is used as the treatment regimen for the remaining weeks to a total duration of 52 weeks (13 cycles) or until disease progression. Each cycle is 4 weeks.

Iscador® P is already approved in Switzerland for the following indications:

Approved in Switzerland as Iscador P for:

• Solid tumors
• Precancerous lesions

Who Is Running the Clinical Trial?

Hackensack Meridian Health

Lead Sponsor

Trials

141

Recruited

42,900+

Susan Zabransky Hughes Foundation

Collaborator

Trials

1

Recruited

30+

Iscador AG, Arlesheim, Switzerland.

Collaborator

Trials

1

Recruited

30+

M.D. Anderson Cancer Center

Collaborator

Trials

3,107

Recruited

1,813,000+

Tackle Kids Cancer

Collaborator

Trials

1

Recruited

30+

Published Research Related to This Trial

The whole mistletoe extract, viscumTT, significantly inhibits the growth of osteosarcoma cells and induces apoptosis, showing strong anti-cancer potential in both in vitro and ex vivo studies.

When combined with standard chemotherapy drugs like doxorubicin, etoposide, and ifosfamide, viscumTT enhances the induction of apoptosis in osteosarcoma cells, suggesting it could be an effective adjuvant therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ViscumTT induces apoptosis and alters IAP expression in osteosarcoma in vitro and has synergistic action when combined with different chemotherapeutic drugs. Kleinsimon, S., Kauczor, G., Jaeger, S., et al.[2022]

The fermented mistletoe extract (Iscador Pini) stimulates T-cells, particularly T-helper cells, and monocytes in peripheral blood mononuclear cells from both healthy and allergic individuals, indicating its potential role in enhancing immune responses.

The immune response to the mistletoe extract resembles a primary immune reaction, as evidenced by changes in T-cell populations, suggesting that it may help in developing memory/effector T-cells rather than just recalling existing immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the stimulatory activity of a fermented mistletoe lectin-1 free mistletoe extract on T-helper cells and monocytes in healthy individuals in vitro. Stein, GM., Berg, PA.[2020]

Three mistletoe extracts (Iscador M Spezial, Iscador Qu Spezial, and Iscador P) were tested on 26 human tumor cell lines and showed no stimulation of tumor growth, even in cell lines previously thought to be sensitive to mistletoe lectin.

The extracts Iscador M Spezial and Iscador Qu Spezial demonstrated significant antitumor activity at high concentrations, comparable to isolated mistletoe lectin 1, suggesting their potential as effective treatments against certain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absence of tumor growth stimulation in a panel of 26 human tumor cell lines by mistletoe (Viscum album L.) extracts Iscador in vitro. Kelter, G., Fiebig, HH.[2020]

Non-fermented mistletoe-extract drugs (AbnobaViscum) specifically expand Vγ9Vδ2 T cells and enhance their anti-cancer activity by inducing the release of cytotoxic granules and cytokines like IFNγ and TNFα.

The mechanism of action for AbnobaViscum involves the butyrophilin BTN3A and does not rely on endogenous phosphoantigens, suggesting a unique pathway for activating Vγ9Vδ2 T cells in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mistletoe-Extract Drugs Stimulate Anti-Cancer Vγ9Vδ2 T Cells. Ma, L., Phalke, S., Stévigny, C., et al.[2021]

Mistletoe extracts, such as Iscador and Helixor, have been used in Germany, Switzerland, and Austria for their immunomodulating and immunostimulating properties, showing potential benefits in cancer treatment based on experimental and clinical studies.

While mistletoe extracts are not a replacement for conventional cancer therapies like chemotherapy and radiotherapy, they may enhance patients' quality of life and potentially extend survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunostimulatory properties of mistletoe extracts and their application in oncology]. Wrotek, S., Skawiński, R., Kozak, W.[2020]

Long-term therapy with Iscador, a mistletoe preparation, may significantly prolong overall survival in cervical cancer patients, with hazard ratios indicating a strong positive effect compared to controls.

Patients receiving Iscador therapy showed significant improvements in psychosomatic self-regulation within 12 months, suggesting benefits beyond just survival, although no effect on tumor progression was observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective controlled cohort studies on long-term therapy of cervical cancer patients with a mistletoe preparation (Iscador). Grossarth-Maticek, R., Ziegler, R.[2020]

Mistletoe extracts can enhance the proliferation of CD4 T cells in cancer patients who have received mistletoe therapy, indicating a potential immune-boosting effect in these individuals.

The strongest T cell response was observed with a specific vesicle preparation of mistletoe extract from apple trees, suggesting that the type of extract may influence its efficacy in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oligoclonal in vitro response of CD4 T cells to vesicles of mistletoe extracts in mistletoe-treated cancer patients. Fischer, S., Scheffler, A., Kabelitz, D.[2019]

Mistletoe extracts from apple and pine trees significantly stimulated the proliferation of CD4+ T cells in cancer patients who had received mistletoe treatment, indicating a potential immunotherapeutic effect.

In contrast, untreated donors only showed T cell activation in response to heat-treated mistletoe extracts, specifically activating gamma delta T cells, suggesting different mechanisms of action based on prior treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stimulation of the specific immune system by mistletoe extracts. Fischer, S., Scheffler, A., Kabelitz, D.[2022]

Combining NY-ESO-1-specific T cells with histone deacetylase inhibitors (HDACis) like panobinostat or vorionstat enhances the effectiveness of these T cells against soft tissue sarcoma (STS) cells, as shown in ex vivo studies.

Pretreatment with HDACis increases the expression of the NY-ESO-1 antigen and HLA-ABC on STS cells, leading to improved T cell activation and cytokine release, suggesting a promising strategy to boost the efficacy of adoptive cell therapy in treating STS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HDAC Inhibition for Optimized Cellular Immunotherapy of NY-ESO-1-Positive Soft Tissue Sarcoma. Gong, W., Wang, L., Schubert, ML., et al.[2022]

Three aqueous mistletoe extracts (Iscador M special, Iscador Qu special, and Iscador P) were tested on 16 human tumor cell lines, showing no evidence of tumor growth stimulation, which addresses concerns about mistletoe extracts potentially promoting cancer growth.

Iscador M special and Iscador Qu special, which have high concentrations of mistletoe lectins, demonstrated significant antitumor activity, inhibiting growth by over 70% in certain cancer cell lines, while Iscador P, lacking mistletoe lectin, showed no antiproliferative effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absence of tumor growth stimulation in a panel of 16 human tumor cell lines by mistletoe extracts in vitro. Maier, G., Fiebig, HH.[2020]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7201820/

Long-Term Follow-up of a Randomized Study of Oral ...

In relapsed osteosarcoma, the 5-yr postrelapse disease-free survival (PRDFS) rate after the second relapse is <20%.

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05726383

Study Details | NCT05726383 | Iscador® P (Mistletoe) ...

This will be a phase II, single arm study of osteosarcoma patients with fully resected pulmonary metastases. The MTD corresponds to the dosage recommendations ...

3.

researchgate.net

researchgate.net/publication/337066589_Long_term_results_in_osteosarcoma_patients_treated_with_Viscum_album_Fermentatum_P_versus_Etoposide_as_maintenance_therapy_after_second_relapse?_iepl%5Bcontexts%5D%5B0%5D=lab_detail&_iepl%5BtargetEntityId%5D=PB%3A337066589&_iepl%5BinteractionType%5D=publicationView

Long term results in osteosarcoma patients treated with ...

Long term results in osteosarcoma patients treated with Viscum album Fermentatum P versus Etoposide as maintenance therapy after second relapse.

4.

mistletoe-therapy.org

mistletoe-therapy.org/scientific-information/clinical-evidence/clinical-studies/osteosarcoma

Mistletoe therapy: Osteosarcoma

Therapy with mistletoe extracts prolonged the disease-free survival time in osteosarcoma patients who had developed a second relapse and improved their quality ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3988743/

A Randomized Study on Postrelapse Disease-Free Survival ...

The Viscum album extract applied in this study is an approved drug and has a marketing authorization under the name “Iscador P” (Weleda AG, ...

6.

cancer.gov

cancer.gov/about-cancer/treatment/cam/hp/mistletoe-pdq

Mistletoe Extracts (PDQ®) - NCI

This cancer information summary provides an overview of the use of mistletoe as a treatment for people with cancer.