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A Pilot Study of Decitabine and Vorinostat With Chemotherapy for Relapsed ALL

Phase 1/Phase 2
1 Year
21 Years
Open (Enrolling)
Acute Lymphoblastic Leukemia, Precursor B-Cell Lymphoblastic Leukemia, Precursor T-Cell Lymphoblastic Leukemia

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Trial Information

A Pilot Study of Decitabine and Vorinostat With Chemotherapy for Relapsed ALL

Decitabine is a demethylating agent and vorinostat is a HDAC inhibitor. The use of
demethylating agents and HDAC inhibitors in combination have been previously shown to have
synergistic effects in altering neoplastic pathways of cancer cells and be well tolerated in
human clinical studies. With the ability of decitabine and vorinostat to alter the abnormal
cellular pathways of leukemic blasts and essentially turn off anti-apoptotic proteins, the
leukemia cells have become primed for cytotoxic cell kill via chemotherapeutic agents. This
study will ask the question as to whether or not the combination of decitabine and
vorinostat followed by chemotherapy is feasible and whether it can positively impact outcome
in patients with relapsed or refractory acute lymphoblastic leukemia.

Inclusion Criteria:

- Patients must be ≥1 and ≤ 21 years of age when originally diagnosed with ALL.


- 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

- 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 ≥

- 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

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

- 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 are unable to swallow capsules.

- 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.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of participants with adverse events.

Outcome Description:

To evaluate the side effects of giving decitabine and vorinostat before and during chemotherapy using the standard drugs vincristine, dexamethasone, PEG-asparaginase and mitoxantrone.

Outcome Time Frame:

6 weeks

Safety Issue:


Principal Investigator

Michael Burke, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of Minnesota Children's Hospital


United States: Food and Drug Administration

Study ID:




Start Date:

December 2011

Completion Date:

Related Keywords:

  • Acute Lymphoblastic Leukemia
  • Precursor B-Cell Lymphoblastic Leukemia
  • Precursor T-Cell Lymphoblastic Leukemia
  • Relapse
  • Lymphoblastic
  • Leukemia
  • Decitabine
  • Vorinostat
  • Refractory
  • Acute
  • Childhood
  • Pediatric
  • ALL
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma



Johns Hopkins UniversityBaltimore, Maryland  21205
Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania  19104
Stanford University Medical CenterStanford, California  94305-5408
Children's National Medical CenterWashington, District of Columbia  20010-2970
Phoenix Children's HospitalPhoenix, Arizona  85016-7710
Children's Hospital Central CaliforniaMadera, California  93638-8762
Childrens Hospital Los AngelesLos Angeles, California  90027
Vanderbilt Children's HospitalNashville, Tennessee  37232-6310
New York University Medical CenterNew York, New York  10016
Oregon Health and Science UniversityPortland, Oregon  97201
Seattle Children's HospitalSeattle, Washington  98105
Children's Mercy Hospitals and ClinicsKansas City, Missouri  64108
Memorial Sloan KetteringNew York, New York  10021
Cook Children's Medical CenterFort Worth, Texas  76104
Dana FarberBoston, Massachusetts  02115-6084
UCSF School of MedicineSan Francisco, California  94143-0106
University of Miami Cancer CenterMiami, Florida  33136
C.S. Mott Children's HospitalAnn Arbor, Michigan  48109-0914
Childrens Hospital & Clinics of MinnesotaMinneapolis, Minnesota  55404-4597
Children's Hospital New York-PresbyterianNew York, New York  10032
Miller Children's HospitalLong Beach, California  90806
Children's MemorialChicago, Illinois  60614
Oakland Children's HospitalOakland, California  
University of Minnesota Children's HospitalMinneapolis, Minnesota  
Nationwide Childrens HospitalColumbus, Ohio  
Levine Children's Hospital at Carolinas Medical CenterCharlotte, North Carolina  28203
Children's Healthcare of Atlanta, Emory UniversityAtlanta, Georgia  
St. JudeMemphis, Tennessee  38105-3678
The Children's Hospital, University of ColoradoAurora, Colorado  80045
University of Texas at SouthwesternDallas, Texas