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A Therapeutic Trial of Bortezomib (Velcade), Vorinostat (SAHA) and Dexamethasone for Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL)

Phase 2
2 Years
30 Years
Not Enrolling
Acute Lymphoblastic Leukemia

Thank you

Trial Information

A Therapeutic Trial of Bortezomib (Velcade), Vorinostat (SAHA) and Dexamethasone for Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL)

This is a phase II study of bortezomib 1.3 mg/m^2 by intravenous pyelogram (IVP) on days 1,
4, 8, and 11, vorinostat 180 mg/m^2 by mouth (PO) per day (not to exceed 400 mg per day)
days 1-14, and dexamethasone 6 mg/m^2 PO days 4-15 for the treatment of relapsed/refractory
acute lymphoblastic leukemia (ALL). No more than 3 treatment courses may be given.

Inclusion Criteria:

- Diagnosis of lymphoblastic lymphoma or acute lymphoblastic leukemia (ALL) with ≥ 5%
blasts in the bone marrow (M2/M3) with or without extramedullary disease that meets
one of the following criteria:

- Refractory Disease/Induction Failure: Failure to achieve initial remission after
2 attempts of standard induction therapy

- Relapsed Disease: Patients in relapse #1 or higher for whom standard curative
therapies or therapies to prolong survival do not exist.

Patients who are Philadelphia chromosome-positive (Ph + ALL) are eligible provided they
are not imatinib resistant or intolerant.

Patients with CNS positive disease will be eligible.

- Age 2 to 30 years

- Karnofsky ≥ 50% for patients 16 years and older and Lansky status ≥ 50 for patients
under 16 years of age.

- Patients must have a life expectancy ≥ 8 weeks as determined by the enrolling

- Have acceptable organ function as defined within 7 days of starting treatment:

- Renal: creatinine clearance ≥ 70ml/min/1.73m^2 or serum creatinine based on
age/gender as follows: Maximum serum creatinine (mg/dl) 0.8 for 2 years to <6
years; 1.0 for 6 years to <10 years; 1.2 for 10 years to <13 years; 1.5 male and
1.4 female for 13 years to <16 years; 1.7 male and 1.4 female for ≥ 16 years

- Hepatic: ALT < 5 x upper limit of normal (ULN) and total bilirubin ≤ 1.5x upper
limit of normal (ULN) for age.

- Cardiac: left ventricular ejection fraction ≥ 40% by echocardiogram/multi gated
acquisition scan (ECHO/MUGA). Normal QTc on electrocardiogram (EKG) (not to
exceed upper limit of normal - men: 430 milliseconds (ms); women: 450 ms;
children up to 15 years: 440 ms).

- Prior Therapy:

- Patients must have recovered from the non-hematologic toxic effects of all prior
therapy before entry onto this trial. Recovery is defined as a Common Toxicity
Criteria for Adverse Events (CTCAE) version 4.0 toxicity grade <2, unless
otherwise specified in the Inclusion and Exclusion Criteria.

Cytotoxic therapy: Patients must have had their last dose of chemotherapy at least two
weeks prior to study entry.

- Hematopoietic growth factors: At least 7 days since the completion of therapy with a
growth factor and at least 14 days since pegfilgrastim (Neulasta®) administration.

- Biologic (anti-neoplastic) therapy: At least 7 days since the completion of therapy
with 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.

- Monoclonal antibodies: At least 3 half-lives of the antibody after the last
administration of a monoclonal antibody.

- Hematopoietic Stem Cell Transplant (HSCT): Patients who have experienced their
relapse after a HSCT are eligible, provided they have no evidence of
Graft-versus-Host Disease (GVHD).

- Women of child bearing potential must agree to use adequate contraception
(diaphragm, birth control pills, injections, intrauterine device [IUD], surgical
sterilization, subcutaneous implants, or abstinence, etc.) for the duration of
treatment and for 2 months after the last dose of chemotherapy. Sexually active
men must agree to use barrier contraceptive for the duration of treatment and
for 2 months after the last dose of chemotherapy.

- Voluntary written consent before performance of any study-related procedure not
part of normal medical care, with the understanding that consent may be
withdrawn by the subject/guardian at any time without prejudice to future
medical care.

Exclusion Criteria:

- Pregnant or lactating. The agents used in this study are known to be teratogenic to a
fetus and there is no information on the excretion of agents into breast milk.
Confirmation that the subject is not pregnant must be established by a negative serum
beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during
screening. Pregnancy testing is not required for surgically sterilized women.

- Known hypersensitivity to bortezomib, boron or mannitol or any of the agents or their
ingredients used in this study.

- Inability to swallow capsules.

- Grade 2 or greater peripheral neuropathy within 14 days before study registration.

- Patients with untreated positive blood cultures or progressive infections as assessed
by radiographic studies.

- Myocardial infarction within 6 months prior to enrollment or has New York Heart
Association (NYHA) Class III or IV heart failure (appendix VI), uncontrolled angina,
severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of
acute ischemia or active conduction system abnormalities. Prior to study entry, any
ECG abnormality at Screening has to be documented by the investigator as not
medically relevant.

- Serious concomitant medical or psychiatric disorders (e.g., active infection,
uncontrolled diabetes) that, in the opinion of the investigator, would compromise the
safety of the patient or likely to interfere with participation in this clinical

- Diagnosed or treated for another malignancy within 3 years of enrollment, with the
exception of complete resection of basal cell carcinoma or squamous cell carcinoma of
the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.

- Patient has received investigational drugs within the 14 days before study

- Radiation therapy within 3 weeks before registration. Enrollment of patients who
require concurrent radiotherapy (which must be localized in its field size) should be
deferred until the radiotherapy is completed and 3 weeks have elapsed since the last
date of therapy.

Type of Study:


Study Design:

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

Outcome Measure:

Remission Rate in ALL Patients

Outcome Description:

To determine the efficacy in terms of end of induction (Day 30) remission rates for bortezomib, vorinostat and dexamethasone when administered in combination for patients aged 2-30 years with relapsed/refractory acute lymphoblastic leukemia (ALL).

Outcome Time Frame:

Day 30

Safety Issue:


Principal Investigator

Michael Burke, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Masonic Cancer Center, University of Minnesota


United States: Food and Drug Administration

Study ID:




Start Date:

June 2011

Completion Date:

January 2013

Related Keywords:

  • Acute Lymphoblastic Leukemia
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma



Masonic Cancer Center, University if MinnesotaMinneapolis, Minnesota  55455