Everolimus With Multiagent Re-Induction Chemotherapy in Pediatric Patients With ALL (CRAD001NUS175T)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Dana-Farber Cancer Institute
Information provided by (Responsible Party):
Lewis B. Silverman, M.D., Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
First received: January 30, 2012
Last updated: September 8, 2014
Last verified: September 2014

Laboratory and other studies suggest that, the study drug, Everolimus (RAD001), may prevent tumor cell growth and also may increase the efficacy of other chemotherapy drugs. Everolimus is approved for use in the United States for certain types of cancer, such as kidney cancer. It has been extensively studied in people with various types of cancer as a single agent (a drug that is used alone to treat the cancer) or in combination with a number of other drugs. Studies in adults with cancer have also evaluated Everolimus in combination with other anti-tumor drugs. Information from lab studies and some other clinical trials suggests that Everolimus may kill leukemia cells on its own, and also make it more likely that steroids (such as prednisone) are able to kill leukemia cells.

In this research study, we are looking to learn more about how Everolimus works in combination with other drugs which are commonly used to treat relapsed acute lymphoblastic leukemia (prednisone, vincristine, PEG-asparaginase, and doxorubicin). The main goal of the study is to evaluate the side effects of this treatment combination in order to determine a safe dose of Everolimus which can be given with these other 4 drugs.

Condition Intervention Phase
Acute Lymphoblastic Leukemia
Drug: Everolimus
Drug: Prednisone
Drug: Vincristine
Drug: PEG-Asparaginase
Drug: Doxorubicin
Drug: Dexrazoxane
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:

Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Safety and Feasibility [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    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)

Secondary Outcome Measures:
  • Clinical Activity [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To investigate the clinical activity (complete remission rate and levels of end-reinduction MRD) of everolimus in combination with vincristine, prednisone, PEG-asparaginase and doxorubicin in patients with ALL.

  • Impact on biologic markers [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To assess the impact of everolimus therapy when given in combination with vincristine, prednisone, PEG-asparaginase and doxorubicin on biologic markers of glucocorticoid resistance including levels of AKT, MCL1 and phosphorylated S6 ribosomal protein (PS6).

  • Determinants of Response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To explore possible determinants of response (as measured by peripheral blast clearance, MRD levels and CR status) to everolimus in combination with multi-agent therapy including measurements of anti-apoptotic proteins (BCL2, BCLxL and MCL1), genome-wide gene expression profliling, BH3 profiling and OncoMap profiling.

Estimated Enrollment: 42
Study Start Date: November 2011
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Everolimus
    Orally, daily days 1-32 per assigned dose level
    Other Name: RAD-001
    Drug: Prednisone
    40 mg/m2/day orally 3 x daily days 4-32
    Drug: Vincristine
    1.5 mg/m2 IV daily on days 4, 11, 18, and 25
    Drug: PEG-Asparaginase
    2,500 U/m2 IV 1 x daily on days 5 and 18
    Other Name: Oncaspar
    Drug: Doxorubicin
    30 mg/m2 IV on days 4 and 5
    Drug: Dexrazoxane
    300 mg/m2 IV on days 4 and 5
    Other Name: Zinecard
Detailed Description:

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.


Ages Eligible for Study:   18 Months to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • ALL in first bone marrow relapse occuring > 18 months from initial diagnosis
  • Normal organ function
  • Maximum prior cumulative doxorubicin dose of </= 360 mg/m2 or equivalent

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01523977

Contact: Lewis Silverman, MD 617-632-6191 lewis_silverman@dfci.harvard.edu

United States, Colorado
Children's Hospital Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Lia Gore, MD    720-777-6772    lia.gore@ucdenver.edu   
Principal Investigator: Lia Gore, MD         
United States, Georgia
Children's Healthcare of Atlanta Recruiting
Atlanta, Georgia, United States, 30322
Contact: Todd Cooper, DO    404-785-3535    todd.cooper@choa.org   
Principal Investigator: Todd Cooper, DO         
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago Recruiting
Chicago, Illinois, United States, 60611
Contact: Noboku Hijiya, MD    312-227-4090    NHijiya@luriechildrens.org   
Principal Investigator: Noboku Hijiya, MD         
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Lewis Silverman, MD    617-632-6191    lewis_silverman@dfci.harvard.edu   
Principal Investigator: Lewis Silverman, MD         
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 12549
Contact: Maria Luisa Sulis, MD    212-305-5808    mls95@columbia.edu   
Principal Investigator: Maria Luisa Sulis, MD         
United States, Washington
Seattle Children's Hospital Recruiting
Seattle, Washington, United States, 98105
Contact: Phoenix Ho, MD    206-987-2106    Phoenix.ho@seattlechildrens.org   
Principal Investigator: Phoenix Ho, MD         
Sponsors and Collaborators
Dana-Farber Cancer Institute
Principal Investigator: Lewis Silverman, MD Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: Lewis B. Silverman, M.D., Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01523977     History of Changes
Other Study ID Numbers: 11-237
Study First Received: January 30, 2012
Last Updated: September 8, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:

Additional relevant MeSH terms:
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on July 28, 2015