LeukemiaPhase 1NCT00001251
Phase I Study of Intrathecal Mafosfamide
A Phase 1 study testing Mafosfamide in people with Leukemia and Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
The purpose of this study is to determine efficacy of intrathecal mafosfamide, a preactivated derivative of cyclophosphamide against meningeal malignancies refractory to conventional therapy (radiation therapy and chemotherapy). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Leukemia, Lymphoma, Meningeal Neoplasm
- What is being tested?
- Mafosfamide
- How many people
- 65 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 1989to Nov 2003
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- All patients over 3 years of age with meningeal malignancies that are progressive or refractory to conventional therapy will be eligible for this study. Patients with meningeal malignancies secondary to an underlying solid tumor are eligible at initial diagnosis if there is no conventional therapy.
- Diagnosis: Patients with leukemia, lymphoma, or other solid tumor who also have overt meningeal involvement by their tumor. The definition of meningeal disease on this protocol includes:
- Leukemia/Lymphoma - CSF cell count greater than or equal to 5/mm(3) AND evidence of blast cells on cytospin preparation or by cytology.
- Solid tumors - Presence of tumor cells on cytospin preparation or cytology OR presence of measurable meningeal disease on CT or MRI scans.
- Patients must have a life expectancy of at least 8 weeks and an ECOG performance status of 2 or better. Patients who are unable to walk because of paralysis, but who are up in a wheelchair will be considered ambulatory for the purposes of the performance score.
- Patients and/or their parents must sign an informed consent indicating that they are aware of the investigational nature of this study.
Show all 9Show fewer
- Patients must have recovered from the acute toxic effects of all prior intrathecal chemotherapy, immunotherapy, or radiotherapy, prior to entering this study and must be without significant systemic illness (e.g. infection). Patients must not have received any CNS therapy within 1 week prior to starting treatment on this study or craniospinal irradiation within 8 weeks prior to starting treatment on this study. Patients must not have received intrathecal chemotherapy within 1 week (2 weeks if prior DTC101).
- Patients must not have clinically significant abnormalities with regard to liver function, renal function or metabolic parameters (electrolytes, calcium and phosphorus).
- A Durable Power of Attorney (DPA) must be offered to all patients greater than or equal to 18 years of age.
Who cannot join
- Patients receiving other therapy (either intrathecal or systematic) designed specifically to treat their meningeal malignancy are not eligible for this study. However, patients receiving concomitant chemotherapy to control systemic or bulk CNS disease will be eligible, provided the systemic chemotherapy is not a phase I agent, an agent which significantly penetrates the CNS (e.g., high dose methotrexate, (greater than 1 gm/m(2)), thiotepa, high dose cytarabine, (greater than 2 gm/m(2) per day), 5-fluorouracil, intravenous 6-mercaptopurine or topotecan), or an agent known to have serious unpredictable CNS side effects. Careful documentation of systemic drugs being administered concurrently is required.
- Patients with clinical evidence of obstructive hydrocephalus or compartmentalization of the CSF flow as documented by a radioisotope Indium(111) or Technitium(99) - DTPA flow study are not eligible for this protocol. If a CSF flow block or compartmentalization is demonstrated, focal radiotherapy to the site of the block to restore flow and a repeat CSF flow study showing clearing of the blockage is required for the patient to be eligible for the study.
- Patients who have leukemia or lymphoma and a concomitant bone marrow relapse are not eligible for this study.
- Women of childbearing age must not be pregnant or lactating.
- Patients who have received any other systemic investigational agent within 14 days prior to, or during, study treatment. The 14 day period should be extended if the patient received any investigational agent which is known to have delayed toxicities after 14 days. Patients must not have received any other intrathecal investigational agent within 7 days prior to, or during, study treatment. The 7 day period should be extended if the patient received any investigational agent which is known to have delayed toxicities after 7 days or a prolonged half-life.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Cancer Institute (NCI)
Bethesda, Maryland, 20892
About this study
The purpose of this study is to determine efficacy of intrathecal mafosfamide, a preactivated derivative of cyclophosphamide against meningeal malignancies refractory to conventional therapy (radiation therapy and chemotherapy). The maximally tolerated dose for intrathecal mafosfamide will be established in a limited dosage escalation schedule. The CSF pharmacokinetics of intrathecal mafosfamide will also be studied.
Mafosfamide will be administered intrathecally on a bi-weekly basis for four weeks, followed by twice monthly administration for four months and then monthly IT administration. A minimum of 9 patients will be studied in each disease category (leukemias, lymphomas, and other malignancies refractory to conventional therapy).
Read the detailed description
The purpose of this study is to determine efficacy of intrathecal mafosfamide, a preactivated derivative of cyclophosphamide against meningeal malignancies refractory to conventional therapy (radiation therapy and chemotherapy). The maximally tolerated dose for intrathecal mafosfamide will be established in a limited dosage escalation schedule. The CSF pharmacokinetics of intrathecal mafosfamide will also be studied.
Mafosfamide will be administered intrathecally on a bi-weekly basis for four weeks, followed by twice monthly administration for four months and then monthly IT administration. A minimum of 9 patients will be studied in each disease category (leukemias, lymphomas, and other malignancies refractory to conventional therapy).
- Conditions
- Leukemia, Lymphoma, Meningeal Neoplasm
- Being tested
- Mafosfamide
- Keywords
- Meningeal Malignancy, Pediatric, Alkylating Agents
- Medical subject headings
- Leukemia, Lymphoma, Meningeal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MafosfamideDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study startNov 1989
- Study completionNov 2003
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Enrolment
- 65 participants
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001251
- Sponsor's protocol ID
- 900095
- Other IDs
- 90-C-0095
- Status last verified
- Nov 2003
- First submitted
- 7 Jul 2006
- Last updated
- 19 Aug 2013
- Results posted
- No
Publications
Atassi G, Hilgard P, Pohl J. Antineoplastic activity of ASTA Z 7557 (NSC-345842, INN mafosfamide) on transplantable murine tumors. Invest New Drugs. 1984;2(2):169-73. doi: 10.1007/BF00232347.
PubMed 6469511Bruntsch U, Groos G, Hiller TA, Wandt H, Tigges FJ, Gallmeier WM. Phase-I study of mafosfamide-cyclohexylamine (ASTA-Z-7557, NSC 345 842) and limited phase-I data on mafosfamide-lysine. Invest New Drugs. 1985;3(3):293-6. doi: 10.1007/BF00179434.
PubMed 4066222Arndt CA, Colvin OM, Balis FM, Lester CM, Johnson G, Poplack DG. Intrathecal administration of 4-hydroperoxycyclophosphamide in rhesus monkeys. Cancer Res. 1987 Nov 15;47(22):5932-4.
PubMed 3664493
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Intrathecal Mafosfamide
- ClinicalTrials.gov ID
- NCT00001251
- Acronym / sponsor ID
- 900095
- Conditions
- Leukemia, Lymphoma, Meningeal Neoplasm
- Keywords
- Meningeal Malignancy, Pediatric, Alkylating Agents
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Nov 1989
- Study completion
- Nov 2003
- First posted
- 4 Nov 1999 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine efficacy of intrathecal mafosfamide, a preactivated derivative of cyclophosphamide against meningeal malignancies refractory to conventional therapy (radiation therapy and chemotherapy). The maximally tolerated dose for intrathecal mafosfamide will be established in a limited dosage escalation schedule. The CSF pharmacokinetics of intrathecal mafosfamide will also be studied.
Mafosfamide will be administered intrathecally on a bi-weekly basis for four weeks, followed by twice monthly administration for four months and then monthly IT administration. A minimum of 9 patients will be studied in each disease category (leukemias, lymphomas, and other malignancies refractory to conventional therapy).
Detailed description
The purpose of this study is to determine efficacy of intrathecal mafosfamide, a preactivated derivative of cyclophosphamide against meningeal malignancies refractory to conventional therapy (radiation therapy and chemotherapy). The maximally tolerated dose for intrathecal mafosfamide will be established in a limited dosage escalation schedule. The CSF pharmacokinetics of intrathecal mafosfamide will also be studied.
Mafosfamide will be administered intrathecally on a bi-weekly basis for four weeks, followed by twice monthly administration for four months and then monthly IT administration. A minimum of 9 patients will be studied in each disease category (leukemias, lymphomas, and other malignancies refractory to conventional therapy).
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- All patients over 3 years of age with meningeal malignancies that are progressive or refractory to conventional therapy will be eligible for this study. Patients with meningeal malignancies secondary to an underlying solid tumor are eligible at initial diagnosis if there is no conventional therapy.
- Diagnosis: Patients with leukemia, lymphoma, or other solid tumor who also have overt meningeal involvement by their tumor. The definition of meningeal disease on this protocol includes:
- Leukemia/Lymphoma - CSF cell count greater than or equal to 5/mm(3) AND evidence of blast cells on cytospin preparation or by cytology.
- Solid tumors - Presence of tumor cells on cytospin preparation or cytology OR presence of measurable meningeal disease on CT or MRI scans.
- Patients must have a life expectancy of at least 8 weeks and an ECOG performance status of 2 or better. Patients who are unable to walk because of paralysis, but who are up in a wheelchair will be considered ambulatory for the purposes of the performance score.
Key exclusion criteria (5 listed)
- Patients receiving other therapy (either intrathecal or systematic) designed specifically to treat their meningeal malignancy are not eligible for this study. However, patients receiving concomitant chemotherapy to control systemic or bulk CNS disease will be eligible, provided the systemic chemotherapy is not a phase I agent, an agent which significantly penetrates the CNS (e.g., high dose methotrexate, (greater than 1 gm/m(2)), thiotepa, high dose cytarabine, (greater than 2 gm/m(2) per day), 5-fluorouracil, intravenous 6-mercaptopurine or topotecan), or an agent known to have serious unpredictable CNS side effects. Careful documentation of systemic drugs being administered concurrently is required.
- Patients with clinical evidence of obstructive hydrocephalus or compartmentalization of the CSF flow as documented by a radioisotope Indium(111) or Technitium(99) - DTPA flow study are not eligible for this protocol. If a CSF flow block or compartmentalization is demonstrated, focal radiotherapy to the site of the block to restore flow and a repeat CSF flow study showing clearing of the blockage is required for the patient to be eligible for the study.
- Patients who have leukemia or lymphoma and a concomitant bone marrow relapse are not eligible for this study.
- Women of childbearing age must not be pregnant or lactating.
- Patients who have received any other systemic investigational agent within 14 days prior to, or during, study treatment. The 14 day period should be extended if the patient received any investigational agent which is known to have delayed toxicities after 14 days. Patients must not have received any other intrathecal investigational agent within 7 days prior to, or during, study treatment. The 7 day period should be extended if the patient received any investigational agent which is known to have delayed toxicities after 7 days or a prolonged half-life.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mafosfamide | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2013.
- Background: PubMed 6469511Atassi G, Hilgard P, Pohl J. Antineoplastic activity of ASTA Z 7557 (NSC-345842, INN mafosfamide) on transplantable murine tumors. Invest New Drugs. 1984;2(2):169-73. doi: 10.1007/BF00232347.
- Background: PubMed 4066222Bruntsch U, Groos G, Hiller TA, Wandt H, Tigges FJ, Gallmeier WM. Phase-I study of mafosfamide-cyclohexylamine (ASTA-Z-7557, NSC 345 842) and limited phase-I data on mafosfamide-lysine. Invest New Drugs. 1985;3(3):293-6. doi: 10.1007/BF00179434.
- Background: PubMed 3664493Arndt CA, Colvin OM, Balis FM, Lester CM, Johnson G, Poplack DG. Intrathecal administration of 4-hydroperoxycyclophosphamide in rhesus monkeys. Cancer Res. 1987 Nov 15;47(22):5932-4.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Mafosfamide in people with Leukemia and Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00001251, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2013.