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A Feasibility Trial of Everolimus (RAD001),an mTOR Inhibitor, Given in Combination With Multiagent Re-Induction Chemotherapy in Pediatric Patients With Relapsed Acute Lymphoblastic Leukemia (ALL)


Phase 1
18 Months
21 Years
Open (Enrolling)
Both
Acute Lymphoblastic Leukemia

Thank you

Trial Information

A Feasibility Trial of Everolimus (RAD001),an mTOR Inhibitor, Given in Combination With Multiagent Re-Induction Chemotherapy in Pediatric Patients With Relapsed Acute Lymphoblastic Leukemia (ALL)


Study Treatment: The study treatment lasts 32 days during which time you will be taking the
study drug Everolimus daily for 32 days in addition to standard chemotherapy drugs. Below
lists the study drug as well as the other drugs you will be receiving to treat your leukemia
during this research study.

Chemotherapy drugs:

1. Everolimus (RAD001): By mouth Daily 1-32

2. Prednisone: By mouth or in the vein Three times daily on days 4-32

3. Vincristine: In the vein Daily on days 4, 11, 18, and 25

4. Doxorubicin: In the vein Once per day on days 4 and 5. A drug called dexrazoxane will
be given with each dose of Doxorubicin to protect the heart from any damage that might
be caused by Doxorubicin.

5. PEG-asparaginase: In the vein Once per day on days 5 and 18

If you have or have had an allergy to PEG-asparaginase, we will give another form of
asparaginase (Erwinia asparaginase). Four doses of Erwinia asparaginase will be given in
the muscle twice a week beginning on Day 5 and then another 4 doses will be given in the
muscle twice a week beginning on Day 15 in place of the scheduled doses of PEG-asparaginase.

In addition to the medications listed above, you will also be receiving intrathecal (IT)
chemotherapy that is given directly into your spinal fluid to treat the leukemia that may
have spread to your brain and spinal fluid. The medicines we will be giving in your spinal
fluid are listed below. The number of times we give chemotherapy into the spinal fluid will
depend on whether or not we see leukemia cells in your spinal fluid on the sample we take on
the first day of the study.

1. Cytarabine on Day 1 (also Day 4 if we see leukemia cells in your spinal fluid on the
screening spinal tap)

2. Triple intrathecal therapy (cytarabine, methotrexate and hydrocortisone)on Days 18 and
32 (if we do not see leukemia cells in your spinal fluid on the screening spinal tap),
or on Days 11, 18, 25 and 32 (if we see leukemia cells in your spinal fluid on the
screening spinal tap)

A drug called leucovorin will be given by mouth or by vein after each dose of triple
intrathecal therapy. Leucovorin is given to prevent mouth sores which might occur after you
get methotrexate in the spinal fluid. Leucovorin will be given three times a day for 24
hours beginning one day after you receive a dose of triple intrathecal therapy.

Portions of this treatment are "routine" or "standard" ways of treating recurrent ALL.
Receiving vincristine, prednisone, PEG asparaginase and doxorubicin along with chemotherapy
in the spinal fluid is a standard treatment for relapsed leukemia. The research part of the
treatment involves giving Everolimus at the same time as these drugs.

Clinical and Lab Exams: During the study, you will have a physical examinations and you
will be asked questions about your general health and specific questions about any problems
that you might be having and any medications you may be taking. You will also have blood
work to check for any side effects to your organs from the study drug and other chemotherapy
drugs. Bone marrow studies will be done at the end of the 32-day treatment period to assess
how you responded to treatment. If you are in remission, a special minimal residual disease
(MRD) test will also be performed from the marrow sample as part of the study.


Inclusion Criteria:



- ALL in first bone marrow relapse occuring > 18 months from initial diagnosis

- Normal organ function

- Maximum prior cumulative doxorubicin dose of
Exclusion Criteria:

- Prior therapy for ALL except for intrathecal (IT) chemotherapy

- Pregnant or lactating

- Individuals whose relapsed ALL harbors a t(9;22)/BCR-ABL fusion

- Individuals whose lymphoblasts have surface immunoglobulin by flow cytometry and/or
t(8;14), t(2;8), or t(8;22)

- Down syndrome

- Prior stem cell transplant

- History of asparaginase-associated pancreatitis

- Active lung disease

- Impairment of gastrointestinal function or gastrointestinal disease

- Severe and/or uncontrolled intercurrent illness

- Documented history of previous or current Hepatitis B or C infection

- History of a different malignancy (other than ALL) unless disease-free for at 5 years
and deemed by the investigators to be at low risk for recurrence of that malignancy

- HIV positive on combination antiretroviral therapy

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety and Feasibility

Outcome Description:

To determine the safety and feasibility of treatment with everolimus in combination with vincristine, prednisone, PEG-asparaginase and doxorubicin in patients with relapsed acute lymphoblastic leukemia (ALL)

Outcome Time Frame:

2 years

Safety Issue:

Yes

Principal Investigator

Lewis Silverman, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Dana-Farber Cancer Institute

Authority:

United States: Food and Drug Administration

Study ID:

11-237

NCT ID:

NCT01523977

Start Date:

November 2011

Completion Date:

Related Keywords:

  • Acute Lymphoblastic Leukemia
  • ALL
  • pediatric
  • relapse
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma

Name

Location

Dana-Farber Cancer InstituteBoston, Massachusetts  02115
Seattle Children's HospitalSeattle, Washington  98105
Columbia University Medical CenterNew York, New York  10032
Children's Hospital ColoradoAurora, Colorado  80045