Mistletoe Immunotherapy for Osteosarcoma

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Katharine Offer

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Hackensack Meridian Health

Must not be taking: Immunostimulants, Immunosuppressives

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

No Placebo Group

Prior Safety Data

Approved in 5 Jurisdictions

Trial Summary

What is the purpose of this trial?

This will be a phase II, single arm study of osteosarcoma patients with fully resected pulmonary metastases. The MTD corresponds to the dosage recommendations of the manufacturer of Iscador® P which is licensed in Sweden, New Zealand, South Korea, Germany and Switzerland for the treatment of solid tumors and precancerous lesions. The study population includes patients with relapse of osteosarcoma in the lung following surgical resection of all gross disease (2nd or greater CR). Following completion of final thoracotomy, they will be treated with Iscador® P at concentrations up to the MTD with surveillance imaging via CT scan to monitor for relapsed disease.

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.

What data supports the effectiveness of the mistletoe treatment for osteosarcoma?

Research shows that mistletoe extracts can stimulate certain immune cells, like T-helper cells and monocytes, which are important for fighting cancer. Although this research is not specific to osteosarcoma, it suggests that mistletoe might help the immune system target cancer cells. ^{1 2 3 4 5}

How is the treatment Iscador P unique for osteosarcoma?

Iscador P is a mistletoe extract used in complementary cancer therapy that focuses on stimulating the immune system rather than directly killing cancer cells, which is different from traditional chemotherapy. Unlike other mistletoe extracts, Iscador P does not contain mistletoe lectin I, which is known for its antitumor activity, making it unique in its approach to potentially enhance the body's natural defenses without directly inhibiting tumor growth. ^{6 7 8 9 10}

Research Team

Katharine Offer

Principal Investigator

Hackensack Meridian Health

Karen Moody, MD

Principal Investigator

MD Anderson

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Iscador® P (Cancer Vaccine)

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.

Participant Groups

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+

Dr. Gregory J. Rokosz

Hackensack Meridian Health

Chief Medical Officer since 2023

DO from New York College of Osteopathic Medicine, JD from Seton Hall University School of Law

Robert C. Garrett

Hackensack Meridian Health

Chief Executive Officer since 2016

Bachelor's degree in Health Administration from Washington University in St. Louis

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+

Dr. Peter WT Pisters

M.D. Anderson Cancer Center

Chief Executive Officer since 2017

MD from University of Western Ontario

Dr. Jeffrey E. Lee

M.D. Anderson Cancer Center

Chief Medical Officer

MD from Stanford University School of Medicine

Tackle Kids Cancer

Collaborator

Trials

1

Recruited

30+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Mistletoe-Extract Drugs Stimulate Anti-Cancer Vγ9Vδ2 T Cells. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

Oligoclonal in vitro response of CD4 T cells to vesicles of mistletoe extracts in mistletoe-treated cancer patients. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Stimulation of the specific immune system by mistletoe extracts. [2022]

4. Germany 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. [2020]

5. Switzerland pubmed.ncbi.nlm.nih.gov

HDAC Inhibition for Optimized Cellular Immunotherapy of NY-ESO-1-Positive Soft Tissue Sarcoma. [2022]

6. England 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. [2022]

7. England pubmed.ncbi.nlm.nih.gov

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

8. Poland pubmed.ncbi.nlm.nih.gov

[Immunostimulatory properties of mistletoe extracts and their application in oncology]. [2020]

9. Switzerland pubmed.ncbi.nlm.nih.gov

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

10. Germany 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. [2020]