Sargramostim for Down Syndrome

Overseen By Neurology Research Partners, CU Department of Neurology

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Colorado, Denver

Must be taking: Hypothyroidism treatments

Must not be taking: Immunosuppressants, NSAIDs, Anticholinergics

Disqualifiers: Pregnancy, Cancer, Seizures, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 20

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether sargramostim, a type of medication, is safe and manageable for young adults with Down syndrome. Participants will receive either sargramostim or a placebo (an inactive substance) over four weeks to observe their body's reactions. It suits individuals with Down syndrome who have a confirmed diagnosis of trisomy 21 and can have a caregiver or partner assist with trial activities. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop taking my current medications for the trial?

You need to be stable on all your current medications for at least 30 days before the trial starts, and you must continue your hypothyroidism treatment if applicable. Chronic use of certain medications like NSAIDs and anti-cholinergic drugs is not allowed.

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

Research shows that sargramostim, also known as GM-CSF, has been tested for safety in people with various health conditions. Studies have found it to be generally well-tolerated and safe.

In one study, participants who received sargramostim experienced no serious side effects from the drug, indicating no major negative reactions linked to the treatment. Another study, which analyzed over 20 years of data from various patients, including those with low white blood cell counts, also found sargramostim to be safe.

Overall, research suggests that sargramostim is safe for humans, with no major safety concerns reported. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike typical treatments for Down syndrome that focus on managing symptoms and improving quality of life, Sargramostim offers a novel approach by potentially targeting the underlying biological mechanisms associated with cognitive impairment in Down syndrome. Sargramostim is a recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) which may have neuroprotective effects and improve brain function. Researchers are excited about this treatment because it taps into the immune system's potential to enhance cognitive ability, representing a shift from traditional symptom management to modifying the disease process itself.

What evidence suggests that sargramostim might be an effective treatment for Down syndrome?

Research has shown that sargramostim, also known as GM-CSF, might improve thinking and memory in people with Down syndrome. In studies with mice, this treatment reversed memory problems and enhanced brain function. Sargramostim is already used in cancer treatment to help the immune system recover more quickly. In this trial, some participants will receive sargramostim to assess its potential cognitive benefits for people with Down syndrome, though further research is needed to confirm these effects. ^{2 4 5 6 7}

Who Is on the Research Team?

Peter Pressman, MD

Principal Investigator

CU Alzheimer's and Cognition Center

Are You a Good Fit for This Trial?

Adults with Down syndrome aged 18-35, who have a caregiver available for support, can participate in this trial. They must be healthy enough to join, not pregnant or planning pregnancy, and live close to the study site. Participants need recent thyroid checks and stable medication use.

Inclusion Criteria

My medications have been the same for the last 30 days.

I have been diagnosed with Down syndrome.

I can give my consent or have someone legally authorized to do so on my behalf.

Exclusion Criteria

I have had seizures, not including fever-related ones as a baby.

My liver isn't working well, or my ALT levels are three times higher than normal.

Your blood pressure is higher than 160 over 95 when checked before the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sargramostim or placebo subcutaneously 5 days per week for 4 consecutive weeks

4 weeks

20 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

16 weeks

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Saline Placebo
• Sargramostim

Trial Overview The trial is testing Sargramostim (GM-CSF), given five days a week for four weeks, against a saline placebo to see if it's safe and tolerable for young adults with Down syndrome.

How Is the Trial Designed?

Group I: Sargramostim Experimental Treatment 1 Intervention

Sargramostim 250 μg/m2/day subcutaneously (5 days per week)

Group II: Placebo Control - Saline Placebo Group 1 Intervention

Placebo equivalent volume subcutaneously (5 days per week)

Sargramostim is already approved in United States, European Union for the following indications:

Approved in United States as Leukine for:

• Bone Marrow Stimulation
• Neutropenia
• Acute Myeloid Leukemia
• Fungal Infections
• Radiation Exposure

Approved in European Union as Leukine for:

• Bone Marrow Stimulation
• Neutropenia
• Acute Myeloid Leukemia

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

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]

In a study analyzing 990 patients treated with sargramostim and matched cohorts receiving filgrastim or pegfilgrastim, sargramostim was associated with a 56% lower risk of infection-related hospitalizations for those undergoing chemotherapy-induced neutropenia.

Patients using sargramostim also experienced significantly lower hospitalization costs, with reductions of 84% compared to filgrastim and 62% compared to pegfilgrastim, highlighting its potential economic benefits in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of hospitalization risk and associated costs among patients receiving sargramostim, filgrastim, and pegfilgrastim for chemotherapy-induced neutropenia. Heaney, ML., Toy, EL., Vekeman, F., et al.[2022]

In a study involving 137 cancer patients undergoing chemotherapy, both sargramostim and filgrastim were found to be well tolerated for preventing chemotherapy-induced neutropenia, with only a slightly higher incidence of mild fever associated with sargramostim.

There were no significant differences in adverse events, hospitalization days, or the need for intravenous antibiotics between the two treatments, indicating that both growth factors are comparably effective in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized trial comparing the tolerability of sargramostim (yeast-derived RhuGM-CSF) and filgrastim (bacteria-derived RhuG-CSF) in cancer patients receiving myelosuppressive chemotherapy. Beveridge, RA., Miller, JA., Kales, AN., et al.[2019]

Sargramostim is effective in accelerating hematologic recovery in patients exposed to bone marrow-suppressing agents, leading to fewer infections and improved survival outcomes in various clinical settings.

As an immune modulator, sargramostim enhances anti-cancer responses when used alongside conventional therapies, showing a favorable safety profile and potential for expanded use in treating immune-related conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sargramostim (rhu GM-CSF) as Cancer Therapy (Systematic Review) and An Immunomodulator. A Drug Before Its Time? Lazarus, HM., Ragsdale, CE., Gale, RP., et al.[2022]

Filgrastim and sargramostim are effective treatments for neutropenia, but their comparative efficacy and safety require further investigation due to insufficient data from randomized trials.

Tolerability of GM-CSF, like sargramostim, may vary based on protein glycosylation, with evidence suggesting that a nonglycosylated version, molgramostim, could have higher toxicity, highlighting the need for more comprehensive studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical applications of colony-stimulating factors: a historical perspective. Sylvester, RK.[2019]

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 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]

Citations

1. partnertx.com partnertx.com/partner-therapeutics-announces-publication-of-results-from-pre-clinical-study-evaluating-recombinant-murine-gm-csf-in-mouse-models-of-down-syndrome-and-normal-aging/

Pre-clinical study with recombinant murine GM-CSF ... Pre-clinical study with recombinant murine GM-CSF reversed cognitive impairment in Dp16 model of Down syndrome and improved cognitive function in aged normal ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8416151/

Sargramostim (rhu GM-CSF) as Cancer Therapy (Systematic ... Sargramostim accelerates hematologic recovery in diverse clinical settings and enhances anti-cancer responses with a favorable safety profile.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01409915

NCT01409915 | Study of the Safety & Efficacy of Leukine® ... Preliminary preclinical results demonstrated that GM-CSF (Granulocyte macrophage colony-stimulating factor, e.g. Leukine®/Sargramostim) rapidly reduced ...

4. withpower.com withpower.com/trial/phase-2-syndrome-8-2022-0fc26

Sargramostim for Down Syndrome · Info for Participants What data supports the effectiveness of the drug Sargramostim for Down Syndrome? Sargramostim, also known as GM-CSF, is known to boost the immune system and ...

5. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/10.1002/trc2.12158

Safety and efficacy of sargramostim (GM‐CSF) in the ... The previous findings that GM-CSF treatment improves cognition in aged WT mice, in the Dp16 mouse model of Down syndrome (DS), which lacks ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05482334?term=AREA%5BBasicSearch%5D(%22down%20syndrome%22%20AND%20%22clinical%20trial%22)&rank=7

Trial to Evaluate Safety and Efficacy of GM-CSF ... This trial protocol is designed to evaluate primarily whether the use of sargramostim (recombinant human GM-CSF), administered five days per week for four ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7988877/

Safety and efficacy of sargramostim (GM‐CSF) in the ... Results. Sargramostim treatment expectedly changed innate immune system markers, with no drug‐related serious adverse events or amyloid‐related ...