A Pilot Study of Decitabine and Vorinostat With Chemotherapy for Relapsed ALL
NCT ID: NCT01483690
Last Updated: 2020-10-27
Study Results
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View full resultsBasic Information
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TERMINATED
PHASE1/PHASE2
23 participants
INTERVENTIONAL
2011-12-31
2015-07-31
Brief Summary
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Detailed Description
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Conditions
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Study Design
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NON_RANDOMIZED
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Initial Dose Level
Decitabine 15 mg/m2/day given IV over 1 hour on days 1 through 7 and days 15 through 21.
Vorinostat: 180 mg/m2/day (Max dose=400 mg daily) given orally on days 3 through 10 and days 17 through 24
Decitabine
10 mg/m2/day given IV over 1 hour on days 1 through 5 and days 15 through 19.
Vorinostat
180 mg/m2/day (Max dose=400mg daily) given orally on days 2 through 7 and days 16 through 21.
Vincristine
1.5 mg/m2/day (Max dose 2 mg) given IV push on days 10, 17, 24 and 31.
Dexamethasone
20 mg/m2/day divided BID given orally on days 8 through 12 and 22 through 26.
Mitoxantrone
10 mg/m2/day given on days 8 and 9 as a short IV infusion over 5-15 minutes; do not infuse over less than 3 minutes
Pegaspargase
2500 international units/m2/day IM or IV on days 10 and 24.
Methotrexate
Given intrathecally to all patients the dose defined by age below.
* 8 mg for patients age 1-1.99
* 10 mg for patients age 2-2.99
* 12 mg for patients 3-8.99 years of age
* 15 mg for patients \>9 years of age
CNS 1 or 2 patients get doses on day 8, 22 and 35 and CNS 3 patients should get doses on day 8, 15, 22, 29 and 35
Modified Dose Level
Decitabine 10 mg/m2/day given IV over 1 hour on days 1 through 5 and days 15 through 19.
Vorinostat: 180 mg/m2/day (Max dose=400 mg daily) given orally on days 2 through 7 and days 16 through 21
Decitabine
10 mg/m2/day given IV over 1 hour on days 1 through 5 and days 15 through 19.
Vorinostat
180 mg/m2/day (Max dose=400mg daily) given orally on days 2 through 7 and days 16 through 21.
Vincristine
1.5 mg/m2/day (Max dose 2 mg) given IV push on days 10, 17, 24 and 31.
Dexamethasone
20 mg/m2/day divided BID given orally on days 8 through 12 and 22 through 26.
Mitoxantrone
10 mg/m2/day given on days 8 and 9 as a short IV infusion over 5-15 minutes; do not infuse over less than 3 minutes
Pegaspargase
2500 international units/m2/day IM or IV on days 10 and 24.
Methotrexate
Given intrathecally to all patients the dose defined by age below.
* 8 mg for patients age 1-1.99
* 10 mg for patients age 2-2.99
* 12 mg for patients 3-8.99 years of age
* 15 mg for patients \>9 years of age
CNS 1 or 2 patients get doses on day 8, 22 and 35 and CNS 3 patients should get doses on day 8, 15, 22, 29 and 35
Interventions
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Decitabine
10 mg/m2/day given IV over 1 hour on days 1 through 5 and days 15 through 19.
Vorinostat
180 mg/m2/day (Max dose=400mg daily) given orally on days 2 through 7 and days 16 through 21.
Vincristine
1.5 mg/m2/day (Max dose 2 mg) given IV push on days 10, 17, 24 and 31.
Dexamethasone
20 mg/m2/day divided BID given orally on days 8 through 12 and 22 through 26.
Mitoxantrone
10 mg/m2/day given on days 8 and 9 as a short IV infusion over 5-15 minutes; do not infuse over less than 3 minutes
Pegaspargase
2500 international units/m2/day IM or IV on days 10 and 24.
Methotrexate
Given intrathecally to all patients the dose defined by age below.
* 8 mg for patients age 1-1.99
* 10 mg for patients age 2-2.99
* 12 mg for patients 3-8.99 years of age
* 15 mg for patients \>9 years of age
CNS 1 or 2 patients get doses on day 8, 22 and 35 and CNS 3 patients should get doses on day 8, 15, 22, 29 and 35
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
Diagnosis
* Patients must have a diagnosis of acute lymphoblastic leukemia (ALL) with ≥ 25% blasts in the bone marrow (M3), with or without extramedullary disease.
* Patients may have CNS 1, 2 or 3 disease.
* Karnofsky \> 50% for patients \> 16 years of age and Lansky \> 50% for patients ≤ 16 years of age.
* Prior Therapy
* Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
* Patients must have had 2 or more prior therapeutic attempts defined as:
* Relapse after going into remission from re-induction for the first or subsequent relapse (ie: 2nd , 3rd, 4th…relapse), OR
* Refractory disease after first or greater relapse and a re-induction attempt, OR
* Failing to go into remission from original diagnosis after 2 previous induction attempts.
* Hematopoietic Stem Cell Transplant: Patients who have experienced their relapse after a HSCT are eligible, provided they have no evidence of Graft-versus-Host Disease (GVHD) and are at least 60 days post-transplant at the time of enrollment.
* Prior anthracycline exposure: Patients must have less than 400 mg/m2 lifetime exposure of anthracycline chemotherapy. (See Appendix II for calculation worksheet)
* Hematopoietic grow factors: It must have been at least 7 days since the completion of therapy with GCSF or other growth factors at the time of enrollment. It must have been at least 14 days since the completion of therapy with pegfilgrastim (Neulasta®).
* Biologic (anti-neoplastic) therapy: It must be at least 7 days after last does of 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
* Monoclonal antibodies: At least 3 half-lives of the antibody must have elapsed after the last dose of monoclonal antibody. (ie. Rituximab=66 days, Epratuzumab=69 days)
* Immunotherapy: At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines.
Renal and Hepatic Function
* Patient's serum creatinine must be ≤ 1.5 x institutional upper limit of normal (ULN) according to age. If the serum creatinine is greater than 1.5 times normal, the patient must have a calculated creatinine clearance or radioisotope GRF ≥ 70mL/min/1.73m2.
* Patient's ALT and AST must be \< 5 x institutional upper limit of norm ULN. The hepatic requirements are waived for patients with known or suspected liver involvement who would otherwise be eligible after consultation with the Study Chair or Vice Chair.
* Patient's total bilirubin must be ≤ 1.5 x ULN. The hepatic requirements are waived for patients with known or suspected liver involvement who would otherwise be eligible.
Cardiac Function:
* Patient must have a shortening fraction ≥ 27% by Echo or an ejection fraction ≥ 50% by MUGA.
Reproductive Function
* Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed prior to enrollment.
* Female patients with infants must agree not to breastfeed their infants while on this study.
* Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study.
Exclusion Criteria
* Patients will be excluded if they have a known allergy to any of the drugs used in the study.
* Patients will be excluded if they have a systemic fungal, bacterial, viral or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment.
* Patients will be excluded if there is a plan to administer non-protocol chemotherapy, radiation therapy, or immunotherapy during the study period.
* Patients will be excluded if they have significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance with the protocol treatment or procedures, interfere with consent, study participation, follow up, or interpretation of study results.
* Patients will be excluded if they have had any positive fungal culture in the last 30 days prior to enrollment.
1 Year
21 Years
ALL
No
Sponsors
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Therapeutic Advances in Childhood Leukemia Consortium
OTHER
Responsible Party
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Principal Investigators
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Michael Burke, MD
Role: STUDY_CHAIR
Medical College of Wisconsin
Locations
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Childrens Hospital Los Angeles
Los Angeles, California, United States
CHOC
Orange, California, United States
UCSF School of Medicine
San Francisco, California, United States
The Children's Hospital, University of Colorado
Aurora, Colorado, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
University of Miami Cancer Center
Miami, Florida, United States
Children's Healthcare of Atlanta, Emory University
Atlanta, Georgia, United States
Lurie Children's Hospital
Chicago, Illinois, United States
Johns Hopkins University
Baltimore, Maryland, United States
Dana Farber
Boston, Massachusetts, United States
C.S. Mott Children's Hospital
Ann Arbor, Michigan, United States
Childrens Hospital & Clinics of Minnesota
Minneapolis, Minnesota, United States
University of Minnesota Children's Hospital
Minneapolis, Minnesota, United States
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, United States
New York University Medical Center
New York, New York, United States
Children's Hospital New York-Presbyterian
New York, New York, United States
Levine Children's Hospital at Carolinas Medical Center
Charlotte, North Carolina, United States
Nationwide Childrens Hospital
Columbus, Ohio, United States
Oregon Health and Science University
Portland, Oregon, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
St. Jude
Memphis, Tennessee, United States
Vanderbilt Children's Hospital
Nashville, Tennessee, United States
University of Texas at Southwestern
Dallas, Texas, United States
Cook Children's Medical Center
Fort Worth, Texas, United States
Seattle Children's Hospital
Seattle, Washington, United States
Children's Hospital at Westmead
Westmead, New South Wales, Australia
Royal Children's Hospital
Brisbane, Queensland, Australia
Sydney Children's Hospital
Sydney, , Australia
Countries
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References
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Burke MJ, Kostadinov R, Sposto R, Gore L, Kelley SM, Rabik C, Trepel JB, Lee MJ, Yuno A, Lee S, Bhojwani D, Jeha S, Chang BH, Sulis ML, Hermiston ML, Gaynon P, Huynh V, Verma A, Gardner R, Heym KM, Dennis RM, Ziegler DS, Laetsch TW, Oesterheld JE, Dubois SG, Pollard JA, Glade-Bender J, Cooper TM, Kaplan JA, Farooqi MS, Yoo B, Guest E, Wayne AS, Brown PA. Decitabine and Vorinostat with Chemotherapy in Relapsed Pediatric Acute Lymphoblastic Leukemia: A TACL Pilot Study. Clin Cancer Res. 2020 May 15;26(10):2297-2307. doi: 10.1158/1078-0432.CCR-19-1251. Epub 2020 Jan 22.
Raetz EA, Bhatla T. Where do we stand in the treatment of relapsed acute lymphoblastic leukemia? Hematology Am Soc Hematol Educ Program. 2012;2012:129-36. doi: 10.1182/asheducation-2012.1.129.
Related Links
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Therapeutic Advances in Childhood Leukemia \& Lymphoma Consortium web site.
Other Identifiers
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T2009-003
Identifier Type: -
Identifier Source: org_study_id