LeukemiaPhase 1NCT00068302
Sirolimus in Treating Young Patients With Relapsed or Refractory Acute Leukemia or Non-Hodgkin's Lymphoma
A Phase 1 study testing sirolimus in people with Leukemia and Lymphoma, run by Children's Hospital of Philadelphia at 1 site in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy such as sirolimus use different ways to stop cancer cells from dividing so they stop growing or die. PURPOSE: This phase I trial is studying the side effects and best dose of sirolimus in treating young patients with relapsed or refractory acute leukemia or non-Hodgkin's lymphoma. Read more about this study
- Who is it for?
- Ages Up to 21 years
- What is being tested?
- sirolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2003to Jul 2013
- 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
DISEASE CHARACTERISTICS:
- Histologically confirmed diagnosis of 1 of the following:
- Acute lymphoblastic leukemia (ALL) OR acute myeloid leukemia (AML)
- At least 25% blasts in the bone marrow
- Recurrent or refractory disease
- Non-Hodgkin's lymphoma (NHL)
- Second or greater relapse as determined by physical or radiological evidence
- Disease for which there is no known curative therapy
PATIENT CHARACTERISTICS:
Age
- 21 and under
Performance status
- Karnofsky 50-100% (patients over 10 years of age)
- Lansky 50-100% (patients 10 years of age and under)
Life expectancy
- At least 4 weeks
Hematopoietic
- Absolute neutrophil count at least 1,000/mm^3*
- Platelet count at least 75,000/mm^3 (transfusion independent)*
- Hemoglobin at least 8.0 g/dL (may receive red blood cells (RBC) transfusions)* NOTE: *Patients with ALL, AML, and NHL with tumor metastatic to bone marrow, with granulocytopenia, anemia, and/or thrombocytopenia are eligible, but will not be evaluable for hematological toxicity
Hepatic
- Bilirubin no greater than 1.5 times normal
- alanine aminotransferase (ALT) no greater than 5 times normal
- Albumin at least 2 g/dL
Renal
- Creatinine based on age, as follows:
- No greater than 0.8 mg/dL (5 years of age and under)
- No greater than 1.0 mg/dL (6 to 10 years of age)
- No greater than 1.2 mg/dL (11 to 15 years of age)
- No greater than 1.5 mg/dL (over 15 years of age) OR
- Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min
Cardiovascular
- Shortening fraction at least 28% by echocardiogram OR
- Ejection fraction at least 50% by gated radionuclide
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Able to ingest oral medication
- No known allergy to sirolimus, tacrolimus, or other mammalian target of rapamycin (mTOR) inhibitors
- No uncontrolled active infection
- Fungal disease must be stable for at least 2 weeks prior to study entry
- Documented negative blood cultures prior to study entry for patients with bacteremia
- No active graft-versus-host disease
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Recovered from prior immunotherapy
- More than 1 week since prior hematopoietic growth factors except for epoetin alfa
- At least 7 days since prior biologic antineoplastic agents
- At least 3 months since prior bone marrow or stem cell transplantation
Chemotherapy
- Recovered from all prior chemotherapy
- More than 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas)
- Prior hydroxyurea within the past 2 weeks is allowed provided peripheral blast count has been stable or rising for at least 3 days
Endocrine therapy
- Prior corticosteroids within the past 2 weeks are allowed provided peripheral blast count has been stable or rising for at least 3 days
Radiotherapy
- Recovered from prior radiotherapy
- At least 2 weeks since prior local palliative radiotherapy
- At least 4 weeks since prior craniospinal radiotherapy or radiation to the pelvis of 50% or more
- At least 4 weeks since prior substantial bone marrow radiotherapy
- No concurrent radiotherapy, except for emergent situations or persistent extramedullary disease with resolution of bone marrow disease
Surgery
- Not specified
Other
- No other concurrent investigational antineoplastic drugs
- No concurrent administration of any of the following:
- Ketoconazole
- Tacrolimus
- Cyclosporine
- Rifampin
- Diltiazem
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
About this study
Official title: A Phase I Trial Of Sirolimus In Relapsed/Refractory Leukemia And Non-Hodgkin's Lymphoma
RATIONALE: Drugs used in chemotherapy such as sirolimus use different ways to stop cancer cells from dividing so they stop growing or die.
PURPOSE: This phase I trial is studying the side effects and best dose of sirolimus in treating young patients with relapsed or refractory acute leukemia or non-Hodgkin's lymphoma.
Read the detailed description
OBJECTIVES:
- Determine the maximum tolerated dose of sirolimus in pediatric patients with refractory or relapsed acute leukemia or non-Hodgkin's lymphoma.
- Determine the dose-limiting toxic effects of this drug in these patients.
- Determine the trough levels produced by this drug in these patients.
- Determine the anti-leukemia/lymphoma activity of this drug in these patients.
OUTLINE: This is an open-label, dose-escalation study.
Patients receive oral sirolimus once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of sirolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Patients are followed for survival.
PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for this study within 2 years.
- Being tested
- sirolimus
- Keywords
- recurrent childhood lymphoblastic lymphoma, recurrent childhood small noncleaved cell lymphoma, recurrent childhood large cell lymphoma, recurrent childhood acute myeloid leukemia, recurrent childhood acute lymphoblastic leukemia
- Medical subject headings
- Leukemia, Lymphoma, Burkitt Lymphoma, Dendritic Cell Sarcoma, Interdigitating, Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sirolimusDrug
Also called rapamycin, Rapamune
3-6 subjects will be enrolled into each dose level
| Study group | Role | What they receive |
|---|---|---|
| Sirolimus | Experimental | This is a dose escalation study including 4-dose levels. Subjects will receive a one-time loading dose of sirolimus on day 0, time 0. Subsequent dosing at the assigned dose level will start 24 hours following the initial loading dose Receives: Drug: sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicity as assessed by Common Toxicity Criteria (CTC) toxicity criteria after the first course of treatment
Subjects will be assessed for toxicity on days 3, 7 and 21
Measured: within 21 days following administration of sirolimus
Secondary outcomes (1)
Response as assessed by radiologic scans after each course of treatment
Response will be assessed on day 21 of cycle 1
Measured: day 21
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2003 (estimated)
- Study startJan 2003
- Primary completionApr 2009
- Study completionJul 2013
Why it stopped: Recruiting/enrolling participants halted prematurely but potentially will resume
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by Children's Hospital of PhiladelphiaThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Philadelphia
- Sponsor type
- University, hospital or other
- Collaborators
- National Childhood Cancer Foundation, The Leukemia and Lymphoma Society
- Responsible party
- Sponsor
- Investigators
- Susan Rheingold, MD, Study chair, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00068302
- Sponsor's protocol ID
- CDR0000321392
- Other IDs
- CHP-755, CHP-IRB-2002-12-3086
- Status last verified
- Jul 2013
- First submitted
- 10 Sep 2003
- Last updated
- 12 Mar 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial Of Sirolimus In Relapsed/Refractory Leukemia And Non-Hodgkin's Lymphoma
- ClinicalTrials.gov ID
- NCT00068302
- Acronym / sponsor ID
- CDR0000321392
- Keywords
- recurrent childhood lymphoblastic lymphoma, recurrent childhood small noncleaved cell lymphoma, recurrent childhood large cell lymphoma, recurrent childhood acute myeloid leukemia, recurrent childhood acute lymphoblastic leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Recruiting/enrolling participants halted prematurely but potentially will resume
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Children's Hospital of PhiladelphiaUniversity, hospital or other
- Collaborators
- National Childhood Cancer Foundation, The Leukemia and Lymphoma Society
- Study start
- Jan 2003
- Primary completion
- Apr 2009 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 11 Sep 2003 (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.
RATIONALE: Drugs used in chemotherapy such as sirolimus use different ways to stop cancer cells from dividing so they stop growing or die.
PURPOSE: This phase I trial is studying the side effects and best dose of sirolimus in treating young patients with relapsed or refractory acute leukemia or non-Hodgkin's lymphoma.
Detailed description
OBJECTIVES:
- Determine the maximum tolerated dose of sirolimus in pediatric patients with refractory or relapsed acute leukemia or non-Hodgkin's lymphoma.
- Determine the dose-limiting toxic effects of this drug in these patients.
- Determine the trough levels produced by this drug in these patients.
- Determine the anti-leukemia/lymphoma activity of this drug in these patients.
OUTLINE: This is an open-label, dose-escalation study.
Patients receive oral sirolimus once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of sirolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Patients are followed for survival.
PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for this study within 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sirolimus | Experimental | Drug: sirolimusThis is a dose escalation study including 4-dose levels. Subjects will receive a one-time loading dose of sirolimus on day 0, time 0. Subsequent dosing at the assigned dose level will start 24 hours following the initial loading dose |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
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 |
|---|---|---|
| sirolimusAlso: rapamycin, Rapamune3-6 subjects will be enrolled into each dose level | Drug | Sirolimus |
Primary outcome
Toxicity as assessed by Common Toxicity Criteria (CTC) toxicity criteria after the first course of treatment
Time frame: within 21 days following administration of sirolimus
Subjects will be assessed for toxicity on days 3, 7 and 21
1 secondary outcome
Response as assessed by radiologic scans after each course of treatment
Time frame: day 21
Results and safety
The study was stopped early (reason given: Recruiting/enrolling participants halted prematurely but potentially will resume). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2015.
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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.
Susan Rheingold, MD study chair
Children's Hospital of Philadelphia
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 in people with Leukemia and Lymphoma, run by Children's Hospital of Philadelphia 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?
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: stopped early, as of the sponsor's last update on 12 Mar 2015. 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 stopped early (reason given: Recruiting/enrolling participants halted prematurely but potentially will resume). Results are not available in the source record.
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?
Toxicity as assessed by Common Toxicity Criteria (CTC) toxicity criteria after the first course of treatment (time frame: within 21 days following administration of sirolimus). 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 12 Mar 2015.