Zoledronic Acid for Cancer

Overseen By Giselle Moore-Higgs, PhD, APRN

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Florida

Must be taking: Zoledronic acid

Disqualifiers: Uncontrolled infection, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4-6 weeks

27 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination to improve survival rates for children and young adults with challenging solid tumors that have returned or resisted other treatments. It combines a special type of stem cell transplant with zoledronic acid, a medication used to treat bone diseases, to determine if this approach can better harness the immune system against tumors. The trial seeks participants aged 6 months to 25 years with certain types of solid tumors that haven't responded well to other treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative approach.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor to get a clear answer.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that certain treatments in stem cell transplants are generally safe. These treatments reduce the risk of graft-versus-host disease (GVHD), where new cells might attack the patient's body. As a result, patients typically do not experience severe immune reactions with this approach.

Regarding zoledronic acid, studies suggest it is safe for treating bone issues. Long-term research has found that different dosing schedules do not increase the risk of bone problems like fractures or pain, indicating the drug is unlikely to cause significant harm over time.

Both treatments have demonstrated promising safety in previous studies, indicating they are generally well-tolerated by patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using alpha/beta T cell and CD19+ B cell depletion alongside zoledronic acid in cancer treatment because it offers a novel approach to tackling the disease. Unlike traditional cancer therapies, which often focus on directly attacking tumors with chemotherapy or radiation, this treatment targets the immune cells that can support cancer growth. By depleting specific T and B cells, the immune system's environment is altered, potentially reducing cancer's ability to thrive. Additionally, zoledronic acid is known for its ability to strengthen bones and may help in preventing bone complications in cancer patients, adding another layer of benefit to this innovative treatment strategy.

What evidence suggests that this trial's treatments could be effective for solid tumors?

Research has shown that using stem cell grafts without certain immune cells, specifically αβ T cells and B cells, effectively treats blood cancers. This method has yielded good results, particularly with partially matched family donors. It reduces complications like GVHD (graft-versus-host disease) and shows promise in improving survival rates.

In this trial, participants will receive a stem cell graft depleted of αβ T cells and CD19+ B cells, combined with zoledronic acid. Zoledronic acid, primarily used to strengthen bones, may also enhance the immune system's ability to fight cancer. Studies in breast cancer have suggested that zoledronic acid can lower the chances of cancer recurrence and improve survival. While more data is needed for other cancer types, combining these treatments is thought to offer potential benefits. ^{1 3 5 6 7}

Who Is on the Research Team?

Jordan Milner, MD

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

This trial is for pediatric and young adult patients (≤25 years old) with specific high-risk solid tumors, including various sarcomas, neuroblastoma, bone cancers like osteosarcoma and Ewing sarcoma that have relapsed or are refractory to treatment. Participants must have a related donor for stem cell transplant, good physical function scores (Karnofsky/Lansky ≥60%), and acceptable lung function. They cannot be enrolled if they have more than one active cancer.

Inclusion Criteria

I do not have more than one active cancer.

I am 25 years old or younger.

My condition is high-risk neuroblastoma that has returned or is not responding to treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a stem cell graft depleted of αβ-T cell and CD19+ B cells in combination with zoledronic acid

4-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including incidence of aGVHD and survival rates

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Alpha/Beta T and B Cell Depletion
• Zoledronic Acid

Trial Overview The study tests the safety of a new therapy combining αβ-T cell/B cell-depleted stem cell transplants with zoledronic acid in children and young adults with certain solid tumors. It aims to enhance the immune system's ability to fight cancer and improve survival rates.

How Is the Trial Designed?

Group I: alpha/beta T cell and CD19+ B cell depleted stem cell graft with zoledronic acid Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

Published Research Related to This Trial

Zoledronic acid (ZOL) has shown potential anticancer activity across various cancer types, with evidence from clinical trials indicating survival benefits for patients with advanced cancers.

In early breast cancer patients, ZOL not only improves disease-free survival but also reduces the presence of tumor cells and decreases the size of residual invasive tumors, suggesting it may have significant clinical benefits beyond its role in preventing skeletal-related events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anticancer evidence for zoledronic acid across the cancer continuum. Costa, L., Harper, P., Coleman, RE., et al.[2018]

In a study of 45 patients with limited metastatic bone cancer, combining zoledronic acid with local radiotherapy resulted in a significantly higher rate of bone recalcification (52.2%) compared to radiotherapy alone (22.7%).

The combination therapy also reduced the formation of new bone metastases (13.0% in the combination group vs. 40.9% in the radiotherapy alone group), indicating a potential benefit in managing metastatic bone cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical analysis of therapeutic effect of zoledronic acid combined with radiotherapy for metastatic bone cancer]. Cheng, J., Xue, J., Wu, HG., et al.[2018]

In a study of 228 women with bone metastases from breast cancer, zoledronic acid significantly reduced the rate of skeletal-related events (SREs) by 39% compared to placebo, indicating its efficacy in managing bone complications.

Zoledronic acid was well tolerated, with a safety profile similar to that of placebo, and did not cause any significant increases in serum creatinine levels, suggesting it is a safe treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zoledronic acid significantly reduces skeletal complications compared with placebo in Japanese women with bone metastases from breast cancer: a randomized, placebo-controlled trial. Kohno, N., Aogi, K., Minami, H., et al.[2022]

In a mouse model of breast cancer, combining the anti-PD-1 antibody with zoledronic acid (ZA) resulted in a stronger anti-tumor response compared to either treatment alone, indicating a potential synergistic effect.

The combination therapy showed no obvious toxicity, suggesting it could be a safe and effective approach for enhancing breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1 blockade in combination with zoledronic acid to enhance the antitumor efficacy in the breast cancer mouse model. Li, Y., Du, Y., Sun, T., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8864664/

Unrelated donor α/β T cell– and B cell–depleted HSCT for ... Outcomes using TCRαβ/CD19-depletion HSCT for patients with hematologic malignancies with haploidentical donors has demonstrated acceptable rates ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05800210

NCT05800210 | Alpha/Beta T Cell and CD19+ B ... This study will assess the safety, efficacy, and feasibility of ⍺/β CD3+ T-cell and CD19+ B-cell depletion in allogeneic stem cell transplantation in ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1083879116302816

Selective Depletion of αβ T Cells and B Cells for Human ... These data indicate that αβ T cell and B cell depletion of HSC grafts from HLA-haploidentical donors was efficient and reproducible. Previous article in ...

4. youtube.com youtube.com/watch?v=ogE1gKdCJHc

Is αβ T-cell/CD19 B-cell Depletion the Best Platform for ... This new technology has really the way in which we perform a pledentical transplant and certainly it has transformed the way in which we perform transplant.

5. nature.com nature.com/articles/cmi201735

B cell regulation in cancer and anti-tumor immunity An emerging body of evidence has recently recognized a role for B cells in modulating the immune response to tumors and lymphoid malignancies.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34872106/

and B cell-depleted HSCT for the treatment of pediatric acute ... Outcome data with TCRαβ/CD19 depletion generally describe haploidentical donors, with relatively few URDs. We hypothesized that TCRαβ/CD19- ...

7. ashpublications.org ashpublications.org/blood/article/130/5/677/36802/Outcome-of-children-with-acute-leukemia-given-HLA

Outcome of children with acute leukemia given HLA ... Children with AL given haplo-HSCT after αβ T- and B-cell depletion are exposed to a low risk of acute and chronic GVHD and NRM. · The leukemia-free, GVHD-free ...