Study Stopped
Toxicity
A Pilot Study of Decitabine and Vorinostat With Chemotherapy for Relapsed ALL
1 other identifier
interventional
23
2 countries
28
Brief Summary
This is a pilot study using decitabine and vorinostat before and during chemotherapy with vincristine, dexamethasone, mitoxantrone, and peg-asparaginase in pediatric patients with acute lymphoblastic leukemia (ALL).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Dec 2011
Typical duration for phase_1
28 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 29, 2011
CompletedFirst Posted
Study publicly available on registry
December 1, 2011
CompletedStudy Start
First participant enrolled
December 1, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 31, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
July 31, 2015
CompletedResults Posted
Study results publicly available
October 27, 2020
CompletedOctober 27, 2020
October 1, 2020
3.7 years
November 29, 2011
September 8, 2020
October 5, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of Participants Who Experienced a Dose Limiting Toxicity (DLT).
To evaluate the side effects of giving decitabine and vorinostat before and during chemotherapy using the standard drugs vincristine, dexamethasone, PEG-asparaginase and mitoxantrone.
6 weeks
Secondary Outcomes (1)
Disease Response Rate After Treatment.
6 weeks
Study Arms (2)
Initial Dose Level
EXPERIMENTALDecitabine 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
Modified Dose Level
EXPERIMENTALDecitabine 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
Interventions
10 mg/m2/day given IV over 1 hour on days 1 through 5 and days 15 through 19.
180 mg/m2/day (Max dose=400mg daily) given orally on days 2 through 7 and days 16 through 21.
1.5 mg/m2/day (Max dose 2 mg) given IV push on days 10, 17, 24 and 31.
20 mg/m2/day divided BID given orally on days 8 through 12 and 22 through 26.
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
2500 international units/m2/day IM or IV on days 10 and 24.
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
Eligibility Criteria
You may qualify if:
- Patients must be ≥1 and ≤ 21 years of age when originally diagnosed with ALL.
- 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
- +12 more criteria
You may not qualify if:
- Patients will be excluded if they are receiving Valproic Acid (VPA) therapy.
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (28)
Childrens Hospital Los Angeles
Los Angeles, California, 90027, United States
CHOC
Orange, California, United States
UCSF School of Medicine
San Francisco, California, 94143-0106, United States
The Children's Hospital, University of Colorado
Aurora, Colorado, 80045, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
University of Miami Cancer Center
Miami, Florida, 33136, 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, 48109-0914, United States
Childrens Hospital & Clinics of Minnesota
Minneapolis, Minnesota, 55404-4597, United States
University of Minnesota Children's Hospital
Minneapolis, Minnesota, United States
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108, United States
New York University Medical Center
New York, New York, 10016, United States
Children's Hospital New York-Presbyterian
New York, New York, 10032, United States
Levine Children's Hospital at Carolinas Medical Center
Charlotte, North Carolina, 28203, 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, 19104, United States
St. Jude
Memphis, Tennessee, 38105-3678, 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, 76104, United States
Seattle Children's Hospital
Seattle, Washington, 98105, 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
Related Publications (2)
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.
PMID: 31969338DERIVEDRaetz 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.
PMID: 23233571DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Clinical Research Coordinator, Consortia
- Organization
- Therapeutic Advancements of Childhood Leukemia and Lymphoma
Study Officials
- STUDY CHAIR
Michael Burke, MD
Medical College of Wisconsin
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- GT60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 29, 2011
First Posted
December 1, 2011
Study Start
December 1, 2011
Primary Completion
July 31, 2015
Study Completion
July 31, 2015
Last Updated
October 27, 2020
Results First Posted
October 27, 2020
Record last verified: 2020-10