Hu3F8 + GM-CSF for Osteosarcoma

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

46 Participants Needed

Trial Summary

What is the purpose of this trial?

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 keep the patient in remission longer and/or prevent recurrence of the disease.

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.

What data supports the effectiveness of the drug GM-CSF (Granulocyte-Macrophage Colony Stimulating Factor) in treating osteosarcoma?

Research shows that GM-CSF can stimulate the growth of certain cancer cells, including osteosarcoma cell lines, and has been used to boost the immune system's response against tumors. It also enhances the function of immune cells, which may help in fighting cancer. ^{1 2 3 4 5}

Is the treatment Hu3F8 + GM-CSF safe for humans?

Sargramostim (GM-CSF) has been used in various treatments and is generally considered safe, but there have been reports of allergic reactions in some people. It can also stimulate certain cancer cells, which might be a concern in some cases. ^{2 3 6 7 8}

How is the drug Hu3F8 + GM-CSF unique for treating osteosarcoma?

The drug Hu3F8 + GM-CSF is unique because it combines a humanized monoclonal antibody (Hu3F8) with GM-CSF, which can enhance the immune system's ability to fight cancer by stimulating certain white blood cells and potentially improving immune responses against tumors. This approach is different from standard chemotherapy as it aims to boost the body's natural defenses to target cancer cells. ^{1 2 3 5 9}

Research Team

Filemon Dela Cruz, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Randomized trial of recombinant human granulocyte-macrophage colony-stimulating factor in pediatric patients receiving intensive myelosuppressive chemotherapy. [2019]

2. England 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. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Human granulocyte-macrophage colony-stimulating factor is a growth factor active on a variety of cell types of nonhemopoietic origin. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Phase II trial of GM-CSF in women with asymptomatic recurrent müllerian tumors. [2010]

5. United States pubmed.ncbi.nlm.nih.gov

Granulocyte-macrophage colony-stimulating factor and the immune system. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

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

7. United States pubmed.ncbi.nlm.nih.gov

Efficacy of lenograstim on hematologic tolerance to MAID chemotherapy in patients with advanced soft tissue sarcoma and consequences on treatment dose-intensity. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor (rhu GM-CSF) as Adjuvant Therapy for Invasive Fungal Diseases. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

The effect of rhGM-CSF on the proliferation of osteogenic sarcoma cells. [2019]