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

NCT05184816 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 21-378
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 7

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

Keywords

Deferoxamine (DFO); 21-378; recurrent; persistent

Outcome Measures

Primary Outcomes (2)

• Frequency of dose-limiting toxicities (DLTs) during Phase Ia (Primary safety endpoint during dose-finding phase)

  Patients are considered evaluable for the primary safety endpoint of DLT if they receive at least one full cycle (twice weekly dosing for 4 weeks) without a DLT or if they experience a DLT at any time during the first cycle of IT-DFO. Per CTCAE version 5.0

  1 year

• Frequency of dose-limiting toxicities (DLTs) during Phase Ib (RP2D of IT-DFO in patients with LM from NSCLC)

  Per CTCAE version 5.0

  1 year

Secondary Outcomes (1)

• objective response rate (ORR)

  1 year

Study Arms (1)

Deferoxamine (DFO)

EXPERIMENTAL

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).

Drug: Deferoxamine (DFO)

Interventions

Deferoxamine (DFO) DRUG

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).

Deferoxamine (DFO)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Center for Experimental Therapeutics: collaborator
• F.M. KIRBY FOUNDATION: collaborator

Study Sites (7)

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

RECRUITING

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553, United States

RECRUITING

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Meningeal Carcinomatosis; Recurrence

Interventions

Deferoxamine

Condition Hierarchy (Ancestors)

Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids

Study Officials

• Jessica Wilcox, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jessica Wilcox, MD

CONTACT

212-639-7573; wilcoxj@mskcc.org

Adrienne Boire, MD,PhD

CONTACT

646-888-3786

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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 Record Dates

• First Submitted: December 22, 2021
• First Posted: January 11, 2022
• Study Start: December 22, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (7)