Hu3F8 + GM-CSF for Osteosarcoma

Not currently recruiting at 2 trial locations

Overseen By Emily Slotkin, MD

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Metastatic disease, Infection, Pregnancy, 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

Compensation: Varies

Number of Visits: 3

Duration: 10 days per cycle, up to 5 cycles

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments, Hu3F8 (an antibody) and GM-CSF (a drug that boosts the immune system), to determine if they can help individuals with osteosarcoma (a type of bone cancer) remain in remission longer and prevent recurrence. It targets those who have completed treatment and are in their second or further remission, with no detectable active cancer. This trial may suit individuals who have had osteosarcoma, are currently in remission, and are open to trying new treatments to prevent recurrence. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it does mention that at least three weeks should have passed since your last cytotoxic therapy, immunotherapy, or radiation therapy before joining the trial.

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

Research has shown that the combination of Humanized 3F8 (Hu3F8) and GM-CSF has been tested for safety in other conditions. In past studies, this combination treated neuroblastoma and was generally well-tolerated by many patients. However, some people experienced side effects like mild to moderate pain, fever, or allergic reactions. More serious side effects, such as increased levels of certain enzymes indicating pancreatitis (inflammation of the pancreas), were less common but did occur.

Since this study is in a later phase, earlier research has provided some evidence of safety. However, joining a trial still involves some uncertainty, and participants should consider these potential risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of hu3F8 and GM-CSF for osteosarcoma because it introduces a novel approach by using a humanized monoclonal antibody, hu3F8, which specifically targets GD2, a molecule often found on osteosarcoma cells. Unlike traditional chemotherapy, which can affect both healthy and cancerous cells, hu3F8 aims directly at the cancer cells, potentially reducing side effects while enhancing effectiveness. Additionally, GM-CSF helps to boost the immune system, working alongside hu3F8 to improve the body's natural response to fight off the cancer. This targeted immunotherapy approach is a promising advancement over the more generalized treatments currently available.

What evidence suggests that Hu3F8 and GM-CSF might be effective for osteosarcoma?

This trial will evaluate the combination of Humanized 3F8 (Hu3F8) with GM-CSF for treating osteosarcoma. Studies have shown that Hu3F8 targets a specific protein on cancer cells, aiding the immune system in identifying and attacking these cells. Patients with similar cancers, such as neuroblastoma, lived longer when treated with an antibody like Hu3F8. GM-CSF enhances the immune system, improving the antibody's effectiveness. This combination aims to prevent cancer recurrence and prolong remission. Although more research is needed, early results offer promise for those battling osteosarcoma. ^{1 2 3 4 6}

Who Is on the Research Team?

Filemon Dela Cruz, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for people aged 1-40 who have recurrent osteosarcoma and are in at least their second complete remission. They must have normal organ function, no overt metastases, not be pregnant or breastfeeding, and can't have had the study drug before. Participants need to agree to use birth control and should not have a life-threatening infection.

Inclusion Criteria

Women of child-bearing potential must be willing to practice an effective method of birth control while on treatment

My cancer is in its second or later complete remission.

My kidney function is within the normal range.

Exclusion Criteria

Pregnant women or women who are breast-feeding

Inability to comply with protocol requirements

My cancer has spread to other parts of my body.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive hu3F8 and GM-CSF over a cycle of 10 days, repeated every 2-4 weeks for up to 5 cycles

10 days per cycle, up to 5 cycles

3 visits per cycle (in-person)

Follow-up

Participants are monitored for event-free survival and time to recurrence

12 months

What Are the Treatments Tested in This Trial?

Interventions

• GM-CSF
• Humanized Monoclonal Antibody 3F8 (Hu3F8)

Trial Overview The trial tests Humanized Monoclonal Antibody 3F8 (Hu3F8) combined with GM-CSF on patients with recurrent osteosarcoma. It aims to see if this combination helps keep patients in remission longer without the cancer coming back.

How Is the Trial Designed?

Group I: humanized anti-GD2 antibody, hu3F8, when combined with GM-CSF Experimental Treatment 2 Interventions

One cycle consists of treatment with hu3F8 at a dose of 2.4mg/kg/dose for 3 days (day 1, 3, and 5) in the presence of subcutaneous (sc) GM-CSF (day -4 through 5). These 3 doses of hu3F8 and 10 days of GM-CSF constitute a treatment cycle. Cycles are repeated at \~2-4 week intervals between first days of hu3F8, through 5 cycles. A maximum of 5 cycles will be administered on protocol. If elevations of amylase and/or lipase (\>Grade 1) or clinical signs suggestive of pancreatitis (e.g. upper abdominal pain) occurs, naxitamab and GM-CSF doses should be held until improvement of toxicity to ≤Grade 1 if laboratory elevations and/or pancreatitis is possibly related to either naxitamab or GM-CSF.

GM-CSF is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Leukine for:

• Neutropenia
• Bone Marrow Transplantation
• Leukemia
• Lymphoma
• HIV Infection

Approved in European Union as Sargramostim for:

• Neutropenia
• Bone Marrow Transplantation
• Leukemia
• Lymphoma

Approved in Canada as Leukine for:

• Neutropenia
• Bone Marrow Transplantation
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Children's Hospital Los Angeles

Collaborator

Trials

257

Recruited

5,075,000+

M.D. Anderson Cancer Center

Collaborator

Trials

3,107

Recruited

1,813,000+

Y-mAbs Therapeutics

Industry Sponsor

Trials

26

Recruited

1,600+

Published Research Related to This Trial

In a study involving 35 patients (18 receiving GM-CSF and 17 controls), GM-CSF did not enhance T cell or natural killer cell recovery after allogeneic stem cell transplantation, contrary to expectations.

However, GM-CSF administration improved dendritic cell reconstitution in patients undergoing autologous stem cell transplantation, suggesting its benefits may vary based on the type of transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Granulocyte-macrophage colony-stimulating factor increases the proportion of circulating dendritic cells after autologous but not after allogeneic hematopoietic stem cell transplantation. Eksioglu, EA., Kielbasa, J., Eisen, S., et al.[2018]

In a study of 15 pediatric patients with malignancies and invasive fungal diseases (IFDs), sargramostim showed a high overall response rate of 92%, indicating its potential effectiveness as an adjunctive treatment for patients who are neutropenic and refractory to antifungal therapy.

A systematic review of 65 cases, including the 15 new patients, demonstrated an overall response rate of 82% for sargramostim in treating IFDs, suggesting it may serve as a valuable immunomodulator for patients with hematological malignancies facing difficult-to-treat fungal infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor (rhu GM-CSF) as Adjuvant Therapy for Invasive Fungal Diseases. Chen, TK., Batra, JS., Michalik, DE., et al.[2022]

A case report described an adverse reaction to sargramostim (rhu GM-CSF) involving symptoms like itching, hives, and throat tightness, highlighting the potential for allergic reactions to this treatment.

Prick skin testing showed that the patient was sensitized to sargramostim but not to filgrastim (rhu G-CSF), suggesting that skin testing could help identify patients at risk for allergic reactions to GM-CSF therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immediate hypersensitivity to human recombinant granulocyte-macrophage colony-stimulating factor associated with a positive prick skin test reaction. Engler, RJ., Weiss, RB.[2017]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02502786?term=GM-CSF&aggFilters=status:not%20rec%20enr%20act&viewType=Table&rank=8

Humanized Monoclonal Antibody 3F8 (Hu3F8) With ... The purpose of this study is to find out what effect an antibody called Humanized 3F8 (Hu3F8) and a drug called GM - CSF have on the patient and whether it can ...

2. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT02502786/

Clinical Trial: NCT02502786 - Osteosarcoma The purpose of this study is to find out what effect an antibody called Humanized 3F8 (Hu3F8) and a drug called GM-CSF have on the patient.

3. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2020-0150.html

A Phase II Study of Humanized Monoclonal Antibody 3F8 ... The purpose of this study is to find out what effect an antibody called Humanized 3F8 (Hu3F8) and a drug called GM-CSF have on the patient.

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2015-01423

Humanized Monoclonal Antibody 3F8 and Sargramostim in ... This phase II trial studies how well humanized monoclonal antibody 3F8 (Hu3F8) and sargramostim work in treating patients with bone cancer (osteosarcoma) ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10961524/

Targeting refractory/recurrent neuroblastoma and ... The survival benefit observed in children with neuroblastoma (NB) and minimal residual disease who received treatment with anti-GD2 monoclonal ...

6. clinicaltrial.be clinicaltrial.be/en/details/73994?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

Humanized Monoclonal Antibody 3F8 (Hu3F8) With ... The purpose of this study is to find out what effect an antibody called Humanized 3F8 (Hu3F8) and a drug called GM-CSF have on the patient and whether it ...