Sargramostim for Down Syndrome

Recruiting in Palo Alto (17 mi)

Overseen by Peter Pressman, MD

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

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

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial protocol is designed to evaluate primarily whether the use of sargramostim (recombinant human GM-CSF), administered five days per week for four consecutive weeks (20 treatment days), will be well tolerated by and safe for use in young adult participants with Down syndrome.

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.

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 help recover blood cells after chemotherapy, which suggests it might help improve immune function in other conditions as well. ^{1 2 3 4 5}

Is sargramostim generally safe for humans?

Sargramostim, also known as rhu GM-CSF, has been used to help recover bone marrow after chemotherapy and has been studied for other uses. Some people have had allergic reactions to it, but these are not well understood. Overall, it has been used in various medical settings, suggesting it is generally considered safe, though specific reactions can occur. ^{2 4 5 6 7}

How is the drug sargramostim unique for treating Down Syndrome?

Sargramostim is unique because it activates a broader range of immune cells compared to other similar drugs, potentially offering a more comprehensive immune response. This broader activation could be beneficial in conditions like Down Syndrome, where immune system support might be needed. ^{3 4 5 6 7}

Research Team

Peter Pressman, MD

Principal Investigator

CU Alzheimer's and Cognition Center

Eligibility Criteria

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

I am between 18-35 years old and have Down syndrome.

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

I have been diagnosed with Down syndrome.

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.

Trial Timeline

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

Treatment Details

Interventions

• Saline Placebo (Other)
• Sargramostim (Cytokine)

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.

Participant Groups

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)

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Aviva Abosch

University of Colorado, Denver

Chief Medical Officer since 2019

MD

Uday B. Kompella

University of Colorado, Denver

Chief Executive Officer since 2015

PhD in Pharmaceutical Sciences

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Dr. Richard J. Hodes

National Institute on Aging (NIA)

Chief Executive Officer since 1993

MD from Harvard Medical School

Dr. Marie Bernard

National Institute on Aging (NIA)

Chief Medical Officer

MD from Harvard Medical School

Findings from Research

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

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

2. Germany 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. [2019]

3. 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]

4. 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]

5. 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]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Sargramostim (rhu GM-CSF) as Cancer Therapy (Systematic Review) and An Immunomodulator. A Drug Before Its Time? [2022]

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

Comparison of hospitalization risk and associated costs among patients receiving sargramostim, filgrastim, and pegfilgrastim for chemotherapy-induced neutropenia. [2022]