Recruiting

Phase 1

DeferoxamineA Study of Deferoxamine (DFO) in People With Leptomeningeal Metastasis

Sponsor:

Memorial Sloan Kettering Cancer Center

Code:

NCT05184816

Conditions

Leptomeningeal Metastases

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Deferoxamine (DFO)

Study Details

Brief summary:

The researchers are doing this study to find out whether deferoxamine (DFO) given intrathecally (directly into the CSF) is a safe treatment for people with leptomeningeal metastasis from solid tumor cancer. The researchers will test different doses of DFO to find the highest dose that causes few or mild side effects. When the dose is found, they will test it in future participants to see whether DFO is a safe and effective treatment for people with leptomeningeal metastasis from solid tumor malignancies. They are also doing this study to see how the body absorbs, distributes, gets rid of, and responds to DFO.

Conditions

Leptomeningeal Metastases

Study ID

NCT05184816

Start date

Dec 22, 2021

Status verified date

Jul, 2026

Completion date

Dec, 2027

Anticipated

Primary completion date

Dec, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

Age ≥ 18 years on the day of consenting to study
ECOG performance status ≤ 2 or KPS ≥ 60.
Life expectancy ≥ 8 weeks in the opinion of the Investigator
LM from any solid tumor malignancy (1a and 1b), that is either:

Newly diagnosed: As evidenced by positive CSF cytology, CTC count >3.0/3.0 mL, or unequivocal radiographic evidence of LM on contrast-enhanced MRI, OR
Recurrent: As evidenced by unequivocal radiographic progression on contrast-enhanced MRI, the development of newly or recurrently positive CSF cytology, or a clinically-relevant rise in CSF CTCs at the discretion of the treating Investigator. There are no restrictions on the number of recurrences.

Persistent: As evidenced by any detectable disease (abnormal leptomeningeal enhancement on contrast-enhanced MRI; positive, suspicious, or atypical cytology; positive CSF CTCs; extrinsic cells on CSF cell count differential; or clinical symptoms attributed to LM) after receiving LM-directed radiation or systemic therapy. This includes patients with stable or partially responding LM who, in the opinion of the investigator, would benefit from additional LM-directed therapy.

Confirmation of solid tumor malignancy (phase 1a and 1b) may be made by histopathologic criteria of any primary or metastatic site. For patients that have not previously undergone internal pathology review at MSKCC, a pathology report confirming the primary malignancy is sufficient.
Patients can have concomitant parenchymal brain metastases at study entry as long as they do not require active treatment or have been previously treated.
Patients with seizure disorders, stable on appropriate antiepileptic therapies, are eligible for this trial.
Patients must have normal CSF flow dynamics at the clinical judgment of the treating investigator, with no obstructive hydrocephalus or ventriculoperitoneal (VP) or ventriculoatrial (VA) shunt.
Patients with isolated intracranial LM progression and stable extracranial disease may enroll on trial. If this population is receiving systemic treatment that is controlling their extracranial disease, they may remain on this regimen during study enrollment provided their LM progression occurred on this regimen.
For patients with both intracranial and extracranial disease progression at the time of study screening, necessitating change to their systemic tumor-directed therapy:
If the new systemic treatment of choice has known CNS activity at the discretion of the Principal Investigator, then they should be monitored on this new regimen for 21 days with confirmation of persistent LM (by neuraxial imaging and CSF reassessment) before enrolling on study.
If the new systemic treatment of choice has no known CNS activity at the discretion of the Principal Investigator, then they may start IT-DFO concurrently with the new systemic treatment.
Examples of systemic CNS-active treatments include but are not limited to: bevacizumab, temozolomide, carmustine, lomustine, etoposide, carboplatin, cisplatin, pemetrexed, doxorubicin, high-dose erlotinib, osimertinib, lorlatinib, lapatinib, tucatinib, capecitabine, dabrafenib, trametinib, vemurafenib, cobimetinib, ipilimumab, nivolumab, pembrolizumab, atezolizumab

Patients must have a functioning Ommaya reservoir prior to the first IT-DFO administration or be an appropriate surgical candidate for Ommaya reservoir placement and agree to Ommaya reservoir placement as standard of care prior to the first IT-DFO administration.
Patients that have screening laboratory values out of range, but not clinically significant, may be considered eligible on a case by case basis deemed by the clinical investigator. Adequate bone marrow and organ function is demonstrated by:
White blood cell (WBC) count ≥ 2.5 K/mcL or if this value is less, an exemption has been granted by the treating physician or primary investigator.
Absolute neutrophil count (ANC) ≥ 1.0 K/mcL
Platelet count ≥ 50 K/mcL at least 7 days from last platelet transfusion, or if this value is less, an exemption has been granted by the treating physician or primary investigator.
Hemoglobin (Hgb) ≥ 8 g/dL, or if this value is less, an exemption has been granted by the treating physician or primary investigator.
Serum creatinine ≤ 1.5 times the upper limit of normal (ULN) or if this value is more, an exemption has been granted by the treating physician or primary investigator.
Serum bilirubin ≤ 1.5 times the ULN; or total bilirubin ≤ 3 times the ULN with direct bilirubin within the normal range in patients with well documented Gilbert Disease or if this value is more, an exemption has been granted by the treating physician or primary investigator.
Serum alanine aminotransferase (ALT) and aspartate aminotransaminase (AST) ≤ 3 times the ULN, unless known hepatic disease wherein may be ≤ 5 times the ULN is acceptable. If this value is more, an exemption must be granted by the treating physician or primary investigator.

Women of child-bearing potential and sexually active males must commit to the use of effective contraception while on study.

Exclusion Criteria:

Any CNS-directed irradiation within 7 days of first dose of IT-DFO.
Patients receiving other therapy (either intrathecal or systemic) designed to treat their LM, with ongoing acceptable control of their LM.
Any contraindication to gadolinium-enhanced MRI
Use of any systemic iron chelators within 4 weeks of first dose
Use of ascorbic acid or prochlorperazine within 2 weeks of first dose
Patients are not allowed to receive whole-brain radiation therapy or craniospinal radiation therapy during study enrollment.
Patients must not have any physical and/or psychiatric illness that would interfere with their compliance and ability to tolerate treatment as per the protocol.
Women may not be pregnant or breastfeeding
Known hypersensitivity orSpecial Characters

Study Design

Enrollment

32 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Deferoxamine (DFO)

This study is an open-label, non-randomized, single-center, dose escalation phase 1a study of intrathecal deferoxamine (IT-DFO) in patients with leptomeningeal metastases (LM) from solid tumor malignancies, followed by a phase 1b dose expansion cohort at the recommended phase 2 dose (RP2D) in patients with LM from solid tumor malignancies. Study objectives will include safety (1a/1b), pharmacokinetics (PK) and pharmacodynamics (PD) of IT-DFO (1a), and preliminary anti-tumoral efficacy in patients with LM solid tumor malignancies (1b).

Interventions

Deferoxamine (DFO)

The accelerated single-patient dose escalation will apply to dosing cohorts 1 through 4 (10mg, 30mg, 60mg, 100mg) and will convert to a 3+3 dose escalation for cohorts 5 through 9 (150mg, 210mg, 280mg, 372mg, 495mg).

Primary outcome measure

Frequency of dose-limiting toxicities (DLTs) during Phase Ia (Primary safety endpoint during dose-finding phase) [ Time Frame: 1 year ]
Frequency of dose-limiting toxicities (DLTs) during Phase Ib (RP2D of IT-DFO in patients with LM from NSCLC) [ Time Frame: 1 year ]

Central Contacts and Locations

Central contacts

Jessica Wilcox, MD

212-639-7573 wilcoxj@mskcc.org

Adrienne Boire, MD,PhD

646-888-3786

Locations

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Recruiting

Basking Ridge, New Jersey, United States, 07920

Contacts

Jessica Wilcox, MD

212-639-7573

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Recruiting

Middletown, New Jersey, United States, 07748

Contacts

Jessica Wilcox, MD

212-639-7573

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Recruiting

Montvale, New Jersey, United States, 07645

Contacts

Jessica Wilcox, MD

212-639-7573

Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)

Recruiting

Commack, New York, United States, 11725

Contacts

Jessica Wilcox, MD

212-639-7573

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Recruiting

Harrison, New York, United States, 10604

Contacts

Jessica Wilcox, MD

212-639-7573

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

Recruiting

New York, New York, United States, 10065

Contacts

Jessica Wilcox, MD

212-639-7573

Adrienne Boire, MD, PhD

646-888-3786

Principal Investigator:

Jessica Wilcox, MD

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Recruiting

Uniondale, New York, United States, 11553

Contacts

Jessica Wilcox, MD

212-639-7573

More Information

Sponsor

Memorial Sloan Kettering Cancer Center

Last update posted

Jul 14, 2026

Last verified

Jul, 2026

Keywords

Deferoxamine (DFO)
21-378
recurrent
persistent

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Memorial Sloan Kettering Cancer Center on 2026-07-14.