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Bortezomib and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia

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ClinicalTrials.gov Identifier: NCT01769209
Recruitment Status : Active, not recruiting
First Posted : January 16, 2013
Last Update Posted : January 23, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Michaela Liedtke, Stanford University

January 14, 2013
January 16, 2013
January 23, 2018
March 2013
September 30, 2017   (Final data collection date for primary outcome measure)
CR rate [ Time Frame: On day 29 at the end of induction therapy ]
Response rates will be evaluated and accompanied by 95% confidence intervals using the binomial distribution. Response rate by categories will be calculated with 95% confidence intervals.
Same as current
Complete list of historical versions of study NCT01769209 on ClinicalTrials.gov Archive Site
  • Progression-free survival (PFS) [ Time Frame: From the start of treatment to disease progression or death, whichever comes first, assessed up to 2 years ]
    Analyzed using Kaplan-Meier survival analysis and accompanied with 95% confidence interval.
  • CR and CRp rate after re-induction [ Time Frame: Up to 2 years ]
    Compared to a historical baseline.
  • Failure-free survival (FFS) [ Time Frame: At 1 year ]
    Analyzed by the Kaplan Meier method. Compared to a historical baseline.
  • Survival percent [ Time Frame: At 1 year ]
    Compared to a historical baseline.
  • Incidence of adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 45 days after completion of treatment ]
    Toxicity profile will be presented by rate of overall toxicity and rates of grade 3 or 4 toxicities analyzed separately and combined. Adverse events will be summarized and accompanied by 95% confidence intervals using binomial distribution.
Same as current
Not Provided
Not Provided
 
Bortezomib and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia
Phase II Study of Subcutaneous Bortezomib in Combination With Chemotherapy in Relapsed/Refractory Adult Acute Lymphoblastic Leukemia
This phase II trial studies how well giving bortezomib together with combination chemotherapy works in treating patients with relapsed or refractory acute lymphoblastic leukemia. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. Determine the response rate of bortezomib in combination with a chemotherapy backbone of doxorubicin (doxorubicin hydrochloride), vincristine (vincristine sulfate), PEG-asparaginase (pegaspargase), and dexamethasone in patients with relapsed/refractory acute lymphoblastic leukemia.

SECONDARY OBJECTIVES:

I. Determine progression free survival. II. Estimate the rate of complete response (CR) and CR with incomplete platelet recovery (CRp) after this re-induction compared to a historical baseline.

III. Estimate failure-free survival (FFS) and survival percent at 1 year compared to a historical baseline.

IV. Assess safety and tolerability of the study drug. V. Determine whether bortezomib induces reactive oxygen species (ROS) in circulating acute lymphoblastic leukemia (ALL) blast cells.

OUTLINE:

Patients receive bortezomib subcutaneously (SC) on days 1, 4, 8, and 11; doxorubicin hydrochloride intravenously (IV) on day 1; pegaspargase IV or intramuscularly (IM) on days 5 and 22; vincristine sulfate IV on days 1, 8, 15, and 22; dexamethasone orally (PO) daily on days 1-14; cytarabine intrathecally (IT) on day 1 and methotrexate intrathecally (IT) on day 15. Patients with central nervous system disease receive intrathecal treatment per investigator's discretion.

After completion of study treatment, patients are followed up every 3 months for up to 2 years.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • B-cell Adult Acute Lymphoblastic Leukemia
  • Ph Positive Adult Acute Lymphoblastic Leukemia
  • Recurrent Adult Acute Lymphoblastic Leukemia
  • T-cell Adult Acute Lymphoblastic Leukemia
  • Drug: bortezomib
    Given SC
    Other Names:
    • LDP 341
    • MLN341
    • VELCADE
  • Drug: doxorubicin hydrochloride
    Given IV
    Other Names:
    • ADM
    • ADR
    • Adria
    • Adriamycin PFS
    • Adriamycin RDF
  • Drug: pegaspargase
    Given IV or IM
    Other Names:
    • L-asparaginase with polyethylene glycol
    • Oncaspar
    • PEG-ASP
    • PEG-L-asparaginase
  • Drug: vincristine sulfate
    Given IV
    Other Names:
    • leurocristine sulfate
    • VCR
    • Vincasar PFS
  • Drug: dexamethasone
    Given PO
    Other Names:
    • Aeroseb-Dex
    • Decaderm
    • Decadron
    • DM
    • DXM
  • Drug: cytarabine
    Given IT
    Other Names:
    • ARA-C
    • arabinofuranosylcytosine
    • arabinosylcytosine
    • Cytosar-U
    • cytosine arabinoside
  • Drug: methotrexate
    Given IT
    Other Name: MTX; amethopterin
Experimental: Treatment (bortezomib, chemotherapy)
Patients receive bortezomib SC on days 1, 4, 8, and 11; doxorubicin hydrochloride IV on day 1; pegaspargase IV or IM on days 5 and 22; vincristine sulfate IV on days 1, 8, 15, and 22; dexamethasone PO daily on days 1-14; cytarabine IT on day 1 and methotrexate IT on day 15. Patients with central nervous system disease receive intrathecal treatment per investigator's discretion.
Interventions:
  • Drug: bortezomib
  • Drug: doxorubicin hydrochloride
  • Drug: pegaspargase
  • Drug: vincristine sulfate
  • Drug: dexamethasone
  • Drug: cytarabine
  • Drug: methotrexate
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
18
17
September 30, 2018
September 30, 2017   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Voluntary written informed 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 at any time without prejudice to future medical care
  • Female subjects who:

    • Are postmenopausal for at least 1 year before the screening visit, OR
    • Are surgically sterile, OR
    • If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 30 days after the last dose of bortezomib, or agree to completely abstain from heterosexual intercourse
  • Male subjects, even if surgically sterilized (i.e., status post vasectomy) who:

    • Agree to practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug, OR
    • Agree to completely abstain from heterosexual intercourse
  • • The patient has relapsed or refractory B or T cell acute lymphoblastic leukemia that has progressed following at least one prior therapy. Ph+ patients are eligible. Relapsed ALL is defined in patients as the reappearance of leukemia cells in the peripheral blood or bone marrow or appearance of extramedullary disease after a complete remission. Refractory ALL is defined in patients as failure to achieve a complete remission after induction therapy. Complete remission is defined by <5% leukemia cells in the bone marrow with recovery of peripheral blood counts. Relapsed disease can be documented by bone marrow biopsy (>5% cells in the bone marrow) or by flow cytometry in the peripheral blood or biopsy of extramedullary disease.
  • Must have received at least one (1) line of prior systemic therapy that may NOT have included VELCADE (bortezomib); patients who have undergone autologous/allogeneic stem cell transplantation are eligible
  • Transplant eligible patients are eligible
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • No poorly controlled intercurrent illness including, but not limited to, ongoing or active infection, poorly controlled diabetes, symptomatic congestive heart failure, or psychiatric illness that in the opinion of the investigator would limit compliance with study requirements
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x upper limit of normal
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) unless elevation is deemed due to leukemia infiltration. In these patients, dose modifications may be required based on standard guidelines.
  • Patients must have adequate renal function defined as creatinine clearance of >= 30 ml/minute (Cockcroft-Gault)

Exclusion Criteria:

  • Patient has > 1.5 x ULN total bilirubin
  • Patient has >= grade 2 peripheral neuropathy
  • Patient had myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevant
  • Patient has hypersensitivity to bortezomib, boron, or mannitol
  • Female subject is pregnant or lactating
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study
  • Diagnosed or treated for another malignancy within 2 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
  • Participation in clinical trials with other investigational agents not included in this trial throughout the duration of this trial
  • Radiation therapy within 3 weeks before randomization; enrollment of subjects 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
  • The patient has been exposed to >= 350mg/m^2 of anthracycline (doxorubicin equivalent)
  • The patient has a left ventricular ejection fraction of < 40%
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01769209
HEMALL0008
NCI-2012-03094 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
Not Provided
Not Provided
Not Provided
Michaela Liedtke, Stanford University
Stanford University
National Cancer Institute (NCI)
Principal Investigator: Michaela Liedtke Stanford University
Stanford University
January 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP