Temsirolimus, Dexamethasone, Mitoxantrone Hydrochloride, Vincristine Sulfate, and Pegaspargase in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia or Non-Hodgkin Lymphoma
A Phase 1 Study of Temsirolimus in Combination With Intensive Re-induction Therapy for Children With Relapsed Acute Lymphoblastic Leukemia and Non-Hodgkin Lymphoma
5 other identifiers
interventional
13
2 countries
31
Brief Summary
This phase I trial studies the side effects and the best dose of temsirolimus when given together with dexamethasone, mitoxantrone hydrochloride, vincristine sulfate, and pegaspargase in treating young patients with relapsed acute lymphoblastic leukemia or non-Hodgkin lymphoma. Temsirolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as dexamethasone, mitoxantrone hydrochloride, vincristine sulfate, and pegaspargase work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving temsirolimus with combination chemotherapy may be and effective treatment for acute lymphoblastic leukemia or non-Hodgkin lymphoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
31 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 21, 2011
CompletedFirst Posted
Study publicly available on registry
July 27, 2011
CompletedStudy Start
First participant enrolled
September 1, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2015
CompletedJuly 10, 2015
March 1, 2015
3.7 years
July 21, 2011
July 9, 2015
Conditions
Outcome Measures
Primary Outcomes (2)
Dose-limiting toxicity of temsirolimus in combination with intensive re-induction chemotherapy graded according to the NCI CTCAE v4.0
A descriptive summary of all toxicities will be reported.
Up to 30 days post-treatment
MTD and/or recommended phase II dose defined as the maximum dose at which fewer than one-third of patients experience dose-limiting toxicity graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0
A descriptive summary of all toxicities will be reported.
Up to day 36
Secondary Outcomes (3)
CR rate according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria
Up to 30 days post-treatment
MRD levels present at the end of induction
Up to 30 days post-treatment
mTOR inhibitor effects on downstream signaling in patient lymphoblasts In vitro and in vivo
Up to 30 days post-treatment
Study Arms (1)
Treatment (temsirolimus, combination chemotherapy)
EXPERIMENTALPatients receive dexamethasone PO or IV on days 1-5 and 15-19; mitoxantrone hydrochloride IV over 30 minutes on days 1-2; temsirolimus IV over 30 minutes on days 1 and 8; vincristine sulfate IV on days 1, 8, 15, and 22; and pegaspargase IV over 1 hour on days 3 and 17. Some patients may also receive methotrexate IT up to 72 hours prior to or on day 1 and on day 8.
Interventions
Given PO or IV
Correlative studies
Given IT
Given IV
Given IV
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- Diagnosis:
- Patients must have second (2nd) or greater relapse of pre-B ALL, T-cell ALL, lymphoblastic lymphoma, or peripheral T-cell lymphoma; patients may not have refractory disease
- Patients with leukemia must have had histologic verification of the malignancy at the most recent relapse, including immunophenotyping to confirm diagnosis
- Disease Status:
- Leukemia: patients with leukemia must have an M3 marrow with or without extramedullary site of relapse OR an M2 bone marrow with an extramedullary site of relapse; patients with central nervous system (CNS) 3 status are not eligible for enrollment
- Lymphoma: patients with non-Hodgkin lymphoma must have either measurable or evaluable disease
- Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
- Karnofsky \>= 50% for patients \> 16 years of age and Lansky \>= 50 for patients =\< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
- Prior Therapy:
You may not qualify if:
- Myelosuppressive chemotherapy:
- Patients with leukemia or lymphoma who relapse while receiving standard maintenance chemotherapy with steroid, vincristine pulses and oral outpatient chemotherapy will not be required to have a waiting period before enrollment onto this study
- Patients who relapse while they are not receiving standard maintenance therapy, must have fully recovered from all acute toxic effects of prior therapy; at least 14 days must have elapsed after the completion of cytotoxic therapy, with the exception of hydroxyurea
- Note: cytoreduction with hydroxyurea in patients can be initiated and continued for up to 24 hours prior to the start of protocol therapy
- Hematopoietic growth factors: at least 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
- Biologic (anti-neoplastic agent): at least 7 days after the last dose of a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
- Immunotherapy: at least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines
- Radiation therapy (XRT): at least 14 days after local palliative XRT (small port); at least 84 days must have elapsed if prior total body irradiation (TBI), craniospinal XRT or if \>= 50% radiation of pelvis; at least 42 days must have elapsed if other substantial bone marrow (BM) radiation
- Stem cell infusion: no evidence of active graft versus (vs.) host disease and at least 84 days must have elapsed after transplant or stem cell infusion
- Study specific limitations on prior therapy: patient may not have received prior therapy with an mTOR inhibitor
- Note: intrathecal (IT) methotrexate (MTX) that is given up to 72 hours prior to initiation of systemic chemotherapy per ADVL1114 counts as protocol therapy and not prior anti-cancer therapy; IT MTX given \> 72 hours prior does not count as protocol therapy
- Platelet count \>= 20,000/mm\^3 (may receive platelet transfusions) to initiate therapy
- Patients must not be known to be refractory to red cell or platelet transfusion
- Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70ml/min/1.73 m\^2 or a serum creatinine based on age/gender as follows:
- mg/dL (1 to \< 2 years of age)
- +32 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (31)
Children's Hospital of Alabama
Birmingham, Alabama, 35233, United States
Phoenix Childrens Hospital
Phoenix, Arizona, 85016, United States
Childrens Hospital of Orange County
Orange, California, 92868, United States
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, 94304, United States
Rady Children's Hospital - San Diego
San Diego, California, 92123, United States
UCSF Medical Center-Parnassus
San Francisco, California, 94143, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, 30322, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611, United States
Riley Hospital for Children
Indianapolis, Indiana, 46202, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, 55404, United States
University of Minnesota Medical Center-Fairview
Minneapolis, Minnesota, 55455, United States
University of Mississippi Medical Center
Jackson, Mississippi, 39216, United States
The Childrens Mercy Hospital
Kansas City, Missouri, 64108, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Columbia University Medical Center
New York, New York, 10032, United States
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, 44106, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390, United States
Baylor College of Medicine
Houston, Texas, 77030, United States
Primary Children's Hospital
Salt Lake City, Utah, 84113, United States
Midwest Children's Cancer Center
Milwaukee, Wisconsin, 53226, United States
Hospital for Sick Children
Toronto, Ontario, M5G 1X8, Canada
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Susan Rheingold
COG Phase I Consortium
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 21, 2011
First Posted
July 27, 2011
Study Start
September 1, 2011
Primary Completion
May 1, 2015
Last Updated
July 10, 2015
Record last verified: 2015-03