Acute Lymphoblastic LeukemiaPhase 1NCT00957320
Study of Sirolimus With PEG-Asparaginase in Acute Lymphoblastic Leukemia (ALL)
A Phase 1 study testing Sirolimus and PEG-asparaginase in people with Acute Lymphoblastic Leukemia, run by Emory University at 1 site in United States.
Trial summary
The goal of this study is to find a safe dose of sirolimus that can be used with a standard dose of L-asparaginase. To find the safe dose, the investigators will give the first patient a very small dose of sirolimus (smaller than the dose used in organ transplant children) and the standard dose of L-asparaginase. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia
- What is being tested?
- Sirolimus and PEG-asparaginase
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2009to Aug 2012
- 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 Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Less than 21 years old.
- Acute lymphoblastic leukemia.
- Second or greater bone marrow relapse or 1st relapse and refractory to at least 2 Attempts at re-induction.
- Life expectancy of at least 8 weeks.
- Fully recovered from the acute toxic effects of all prior therapy.
- Appropriate organ function.
Who cannot join
- Patients with a documented history of ≥ grade 3 local or systemic reactions to PEG-asparaginase.
- Patients with a documented history of anti-E. coli asparaginase antibodies.
- Patients with a history of ≥ grade 3 pancreatitis.
- Patients with an active and uncontrolled infection.
- Patients s/p allogeneic bone marrow transplantation, who are still on immunosuppressants.
- Pregnant or lactating females. Women of childbearing age will agree to use contraception during the protocol.
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- Patients currently receiving other investigational agents, medications, or supplements with a known anti-leukemic effect.
- Other concomitant medications that may alter the metabolism of Sirolimus (See section 7.2).
- Patients who, in the opinion of the investigator, will not be able to comply with safety monitoring requirements of the study.
- Patients with a history of a documented thrombus from previous asparaginase therapy.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Healthcare of Atlanta
Atlanta, Georgia, 30322
About this study
Official title: A Phase I Study of Sirolimus With PEG-Asparaginase in Multiple Recurrent or Refractory Childhood Acute Lymphoblastic Leukemia
The goal of this study is to find a safe dose of sirolimus that can be used with a standard dose of L-asparaginase. To find the safe dose, the investigators will give the first patient a very small dose of sirolimus (smaller than the dose used in organ transplant children) and the standard dose of L-asparaginase. The investigators will then look for side effects. If side effects develop, the investigators will decrease the dose of sirolimus. If they do not, the investigators will increase the dose of sirolimus in the next patient on the study. The investigators will continue this method until fewer than one-third of patients have a side effect that would require stopping the drug or changing the dose.
The investigators plan to enroll up to 15 children with relapsed ALL. The enrolled patients must have recovered from other treatment before starting this study. Also, they cannot have severe side effects from their earlier therapy that will possibly make these drugs less safe.
The investigators will collect information on whether these drugs help to cure the ALL, but the purpose will be to find a dose of sirolimus that does not cause too many side effects when combined with L-asparaginase. This will be explained to the families and they will sign a written consent. The patients will provide either verbal or written assent when appropriate.
Read the detailed description
Multiple relapsed acute lymphoblastic leukemia (ALL) has a very poor cure rate, and there is no standard of care for treatment of these patients. Therefore, we want to combine two chemotherapy drugs to see if they are safe and will help treat these patients. The first agent, L-asparaginase, is used in most patients during their initial treatment for ALL. The second agent, sirolimus, causes death in human leukemia cells in the laboratory. Sirolimus is also used in children who have received kidney or heart transplants to prevent organ rejection. Therefore, the safety and side effects are well known in children.
There are many steps that allow cancer cells to grow in humans. L-asparaginase and sirolimus block two different steps in cell growth. Because of this, we anticipate that these two drugs will work together to lead to more cancer cell death.
The first part of the study will last 1 month for each patient. If the patients have a good response to these two drugs, they will be allowed to continue these drugs for up to 12 months. They will continue on the dose of sirolimus that they received during the first month for the remaining time on the study.
We will also look at the way leukemia cells are responding to these medications in the laboratory. We will not draw any blood or bone marrow samples from the patient unless they already need the procedure done for other tests. The amount of extra blood or bone marrow drawn will not cause the patients any harm. As we do not know what these laboratory tests mean, we will not tell the patients the results during the study.
- Conditions
- Acute Lymphoblastic Leukemia
- Being tested
- Sirolimus, PEG-asparaginase
- Keywords
- leukemia, cancer, oncology, sirolimus, ALL
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
Sirolimus daily po days 1 through 28, Dose level 0: 0.25 mg/m2 po daily Dose level 1: 0.5 mg/m2 po daily Dose level 2: 1 mg/m2 po daily Dose level 3 1.5 mg/m2 po daily Dose level 4 2 mg/m2 po daily
PEG-asparaginaseDrug
Subjects will receive PEG-asparaginase at a fixed weekly dose, as per published reports in relapsed childhood ALL.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Subjects will receive PEG-asparaginase at a fixed weekly dose, as per published reports in relapsed childhood ALL. The dose of sirolimus will be dose escalated following standard phase 1 statistical methods.
For patients with active CNS leukemia, intrathecal methotrexate, hydrocortisone and cytarabine (triple IT) will be administered weekly, with leucovorin rescue at the treating physician's discretion. Receives: Drug: Sirolimus; Drug: PEG-asparaginase |
What is being measured
The primary outcome is the main question the study is designed to answer.
To estimate the maximum tolerated dose (MTD) of sirolimus in children with refractory or recurrent acute lymphoblastic leukemia (ALL) who are concurrently receiving PEG-asparaginase.
Measured: end of study
To determine the dose limiting toxicities of sirolimus in combination with PEG-asparaginase in this Phase I Study.
Measured: end of study
Secondary outcomes (2)
To use phospho-flow to measure the degree of phosphorylation of signaling pathway proteins in response to specific stimulating events in bone marrow derived leukemia cells obtained at the time of study entry and at day 15 and 29.
Measured: end of study
To correlate the signal pathway phosphorylation to clinical response to the chemotherapy regimen used in this study.
Measured: end of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2009 (estimated)
- Study startJun 2009
- Primary completionAug 2012
- Study completionAug 2012
Why it stopped: no patients enrolled, decided not to pursue study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe 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
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Frank Keller, Emory University
- Investigators
- Frank Keller, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00957320
- Sponsor's protocol ID
- IRB00015324
- Other IDs
- Sirolimus
- Status last verified
- Nov 2012
- First submitted
- 11 Aug 2009
- Last updated
- 3 Dec 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Sirolimus With PEG-Asparaginase in Multiple Recurrent or Refractory Childhood Acute Lymphoblastic Leukemia
- ClinicalTrials.gov ID
- NCT00957320
- Acronym / sponsor ID
- IRB00015324
- Conditions
- Acute Lymphoblastic Leukemia
- Keywords
- leukemia, cancer, oncology, sirolimus, ALL
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: no patients enrolled, decided not to pursue study
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Study start
- Jun 2009
- Primary completion
- Aug 2012 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 12 Aug 2009 (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 goal of this study is to find a safe dose of sirolimus that can be used with a standard dose of L-asparaginase. To find the safe dose, the investigators will give the first patient a very small dose of sirolimus (smaller than the dose used in organ transplant children) and the standard dose of L-asparaginase. The investigators will then look for side effects. If side effects develop, the investigators will decrease the dose of sirolimus. If they do not, the investigators will increase the dose of sirolimus in the next patient on the study. The investigators will continue this method until fewer than one-third of patients have a side effect that would require stopping the drug or changing the dose.
The investigators plan to enroll up to 15 children with relapsed ALL. The enrolled patients must have recovered from other treatment before starting this study. Also, they cannot have severe side effects from their earlier therapy that will possibly make these drugs less safe.
The investigators will collect information on whether these drugs help to cure the ALL, but the purpose will be to find a dose of sirolimus that does not cause too many side effects when combined with L-asparaginase. This will be explained to the families and they will sign a written consent. The patients will provide either verbal or written assent when appropriate.
Detailed description
Multiple relapsed acute lymphoblastic leukemia (ALL) has a very poor cure rate, and there is no standard of care for treatment of these patients. Therefore, we want to combine two chemotherapy drugs to see if they are safe and will help treat these patients. The first agent, L-asparaginase, is used in most patients during their initial treatment for ALL. The second agent, sirolimus, causes death in human leukemia cells in the laboratory. Sirolimus is also used in children who have received kidney or heart transplants to prevent organ rejection. Therefore, the safety and side effects are well known in children.
There are many steps that allow cancer cells to grow in humans. L-asparaginase and sirolimus block two different steps in cell growth. Because of this, we anticipate that these two drugs will work together to lead to more cancer cell death.
The first part of the study will last 1 month for each patient. If the patients have a good response to these two drugs, they will be allowed to continue these drugs for up to 12 months. They will continue on the dose of sirolimus that they received during the first month for the remaining time on the study.
We will also look at the way leukemia cells are responding to these medications in the laboratory. We will not draw any blood or bone marrow samples from the patient unless they already need the procedure done for other tests. The amount of extra blood or bone marrow drawn will not cause the patients any harm. As we do not know what these laboratory tests mean, we will not tell the patients the results during the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Sirolimus, Drug: PEG-asparaginaseSubjects will receive PEG-asparaginase at a fixed weekly dose, as per published reports in relapsed childhood ALL. The dose of sirolimus will be dose escalated following standard phase 1 statistical methods. For patients with active CNS leukemia, intrathecal methotrexate, hydrocortisone and cytarabine (triple IT) will be administered weekly, with leucovorin rescue at the treating physician's discretion. |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- Less than 21 years old.
- Acute lymphoblastic leukemia.
- Second or greater bone marrow relapse or 1st relapse and refractory to at least 2 Attempts at re-induction.
- Life expectancy of at least 8 weeks.
- Fully recovered from the acute toxic effects of all prior therapy.
Key exclusion criteria (10 listed)
- Patients with a documented history of ≥ grade 3 local or systemic reactions to PEG-asparaginase.
- Patients with a documented history of anti-E. coli asparaginase antibodies.
- Patients with a history of ≥ grade 3 pancreatitis.
- Patients with an active and uncontrolled infection.
- Patients s/p allogeneic bone marrow transplantation, who are still on immunosuppressants.
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 |
|---|---|---|
| SirolimusSirolimus daily po days 1 through 28, Dose level 0: 0.25 mg/m2 po daily Dose level 1: 0.5 mg/m2 po daily Dose level 2: 1 mg/m2 po daily Dose level 3 1.5 mg/m2 po daily Dose level 4 2 mg/m2 po daily | Drug | 1 |
| PEG-asparaginaseSubjects will receive PEG-asparaginase at a fixed weekly dose, as per published reports in relapsed childhood ALL. | Drug | 1 |
Primary outcome
To estimate the maximum tolerated dose (MTD) of sirolimus in children with refractory or recurrent acute lymphoblastic leukemia (ALL) who are concurrently receiving PEG-asparaginase.
Time frame: end of study
To determine the dose limiting toxicities of sirolimus in combination with PEG-asparaginase in this Phase I Study.
Time frame: end of study
2 secondary outcomes
To use phospho-flow to measure the degree of phosphorylation of signaling pathway proteins in response to specific stimulating events in bone marrow derived leukemia cells obtained at the time of study entry and at day 15 and 29.
Time frame: end of study
To correlate the signal pathway phosphorylation to clinical response to the chemotherapy regimen used in this study.
Time frame: end of study
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2013.
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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.
Frank Keller, MD principal investigator
Emory University
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 Sirolimus and PEG-asparaginase in people with Acute Lymphoblastic Leukemia, run by Emory University 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 6 inclusion and 10 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: withdrawn, as of the sponsor's last update on 3 Dec 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 was withdrawn before enrolling participants, so there are no results.
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.
What does the primary outcome measure?
To estimate the maximum tolerated dose (MTD) of sirolimus in children with refractory or recurrent acute lymphoblastic leukemia (ALL) who are concurrently receiving PEG-asparaginase. (time frame: end of study). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Dec 2013.