RECRUITING

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

Conditions

Leptomeningeal Metastases Deferoxamine (DFO)21-378 recurrent persistent

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Phase 1a/1b Trial of Intrathecal Deferoxamine for Leptomeningeal Metastases

Quick Facts

Study Start:2021-12-22

Study Completion:2024-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05184816

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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. * Adequate bone marrow and organ function as demonstrated by: * White blood cell (WBC) count ≥ 2.5 K/mcL * Absolute neutrophil count (ANC) ≥ 1.0 K/mcL * Platelet count ≥ 50 K/mcL at least 7 days from last platelet transfusion * Hemoglobin (Hgb) ≥ 8 g/dL * Serum creatinine ≤ 1.5 times the upper limit of normal (ULN) * 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 * 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. * Women of child-bearing potential and sexually active males must commit to the use of effective contraception while on study.	* 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 or allergic reaction to iron chelating agents

Inclusion Criteria

Exclusion 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.
* Adequate bone marrow and organ function as demonstrated by:
* White blood cell (WBC) count ≥ 2.5 K/mcL
* Absolute neutrophil count (ANC) ≥ 1.0 K/mcL
* Platelet count ≥ 50 K/mcL at least 7 days from last platelet transfusion
* Hemoglobin (Hgb) ≥ 8 g/dL
* Serum creatinine ≤ 1.5 times the upper limit of normal (ULN)
* 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
* 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.
* Women of child-bearing potential and sexually active males must commit to the use of effective contraception while on study.

* 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 or allergic reaction to iron chelating agents

Contacts and Locations

Study Contact

Adrienne Boire, MD, PhD

CONTACT

646-888-3786

boirea@mskcc.org

Jessica Wilcox, MD

CONTACT

212-639-6767

wilcoxj@mskcc.org

Principal Investigator

Adrienne Boire, MD

PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Study Locations (Sites)

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920

United States

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748

United States

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645

United States

Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)

Commack, New York, 11725

United States

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604

United States

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065

United States

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553

United States

Collaborators and Investigators

Sponsor: Memorial Sloan Kettering Cancer Center

Adrienne Boire, MD, PRINCIPAL_INVESTIGATOR, Memorial Sloan Kettering Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-12-22

Study Completion Date2024-12

Study Record Updates

Study Start Date2021-12-22

Study Completion Date2024-12

Terms related to this study

Keywords Provided by Researchers

Deferoxamine (DFO)
21-378
recurrent
persistent

Additional Relevant MeSH Terms

Leptomeningeal Metastases