We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01523977
Recruitment Status : Completed
First Posted : February 1, 2012
Last Update Posted : August 9, 2022
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Lewis B. Silverman, M.D., Dana-Farber Cancer Institute

Tracking Information
First Submitted Date  ICMJE January 30, 2012
First Posted Date  ICMJE February 1, 2012
Last Update Posted Date August 9, 2022
Study Start Date  ICMJE November 2011
Actual Primary Completion Date January 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 30, 2012)
Safety and Feasibility [ Time Frame: 2 years ]
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)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 30, 2012)
  • Clinical Activity [ Time Frame: 2 years ]
    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 ]
    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 ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Everolimus With Multiagent Re-Induction Chemotherapy in Pediatric Patients With ALL
Official Title  ICMJE 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)
Brief Summary

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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acute Lymphoblastic Leukemia
Intervention  ICMJE
  • 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
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 17, 2019)
22
Original Estimated Enrollment  ICMJE
 (submitted: January 30, 2012)
42
Actual Study Completion Date  ICMJE November 2018
Actual Primary Completion Date January 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Months to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01523977
Other Study ID Numbers  ICMJE 11-237
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Lewis B. Silverman, M.D., Dana-Farber Cancer Institute
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Dana-Farber Cancer Institute
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Novartis
Investigators  ICMJE
Principal Investigator: Lewis Silverman, MD Dana-Farber Cancer Institute
PRS Account Dana-Farber Cancer Institute
Verification Date August 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP