Everolimus With Multiagent Re-Induction Chemotherapy in Pediatric Patients With ALL

NCT01523977 | Completed Phase 1 DMC

• 1 other identifier: 11-237
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 8

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.

Conditions

Acute Lymphoblastic Leukemia

Keywords

ALL; pediatric; relapse

Outcome Measures

Primary Outcomes (1)

• Safety and Feasibility

  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)

  2 years

Secondary Outcomes (3)

• Clinical Activity

  2 years

• Impact on biologic markers

  2 years

• Determinants of Response

  2 years

Interventions

Everolimus DRUG

Orally, daily days 1-32 per assigned dose level

Also known as: RAD-001

Prednisone DRUG

40 mg/m2/day orally 3 x daily days 4-32

Vincristine DRUG

1.5 mg/m2 IV daily on days 4, 11, 18, and 25

PEG-Asparaginase DRUG

2,500 U/m2 IV 1 x daily on days 5 and 18

Also known as: Oncaspar

Doxorubicin DRUG

30 mg/m2 IV on days 4 and 5

Dexrazoxane DRUG

300 mg/m2 IV on days 4 and 5

Also known as: Zinecard

Eligibility Criteria

• Age: 18 Months - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Novartis: collaborator

Study Sites (8)

UCSF

San Francisco, California, 94143, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Columbia University Medical Center

New York, New York, 12549, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence

Interventions

Everolimus; Prednisone; Vincristine; pegaspargase; Doxorubicin; Dexrazoxane

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Aminoglycosides; Glycosides; Carbohydrates; Razoxane; Diketopiperazines; Piperazines; Heterocyclic Compounds, 1-Ring

Study Officials

• Lewis Silverman, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 30, 2012
• First Posted: February 1, 2012
• Study Start: November 1, 2011
• Primary Completion: January 1, 2017
• Study Completion: November 1, 2018
• Last Updated: July 18, 2024

Record last verified: 2024-07

Locations

US (8)