Know Cancer

forgot password

A Phase I Trial Of Sirolimus In Relapsed/Refractory Leukemia And Non-Hodgkin's Lymphoma

Phase 1
21 Years
Open (Enrolling)
Leukemia, Lymphoma

Thank you

Trial Information

A Phase I Trial Of Sirolimus In Relapsed/Refractory Leukemia And Non-Hodgkin's Lymphoma


- 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.

Inclusion Criteria


- 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

- Disease for which there is no known curative therapy



- 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


- 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 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


- Bilirubin no greater than 1.5 times normal

- ALT no greater than 5 times normal

- Albumin at least 2 g/dL


- 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


- Shortening fraction at least 28% by echocardiogram OR

- Ejection fraction at least 50% by gated radionuclide


- 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

- No active graft-versus-host disease


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


- Recovered from all prior chemotherapy

- More than 2 weeks since prior myelosuppressive chemotherapy (4 weeks for

- 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


- 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


- Not specified


- No other concurrent investigational antineoplastic drugs

- No concurrent administration of any of the following:

- Ketoconazole

- Tacrolimus

- Cyclosporine

- Rifampin

- Diltiazem

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Toxicity as assessed by CTC toxicity criteria after the first course of treatment

Safety Issue:


Principal Investigator

Susan Rheingold, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Children's Hospital of Philadelphia



Study ID:




Start Date:

January 2003

Completion Date:

Related Keywords:

  • Leukemia
  • Lymphoma
  • 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
  • Leukemia
  • Lymphoma
  • Lymphoma, Non-Hodgkin



Children's Hospital of Philadelphia Philadelphia, Pennsylvania  19104