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Trial record 11 of 80 for:    "Adult Acute Lymphocytic Leukemia" | "Antineoplastic Agents, Hormonal"

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

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ClinicalTrials.gov Identifier: NCT01769209
Recruitment Status : Completed
First Posted : January 16, 2013
Results First Posted : October 9, 2018
Last Update Posted : November 14, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Michaela Liedtke, Stanford University

Tracking Information
First Submitted Date  ICMJE January 14, 2013
First Posted Date  ICMJE January 16, 2013
Results First Submitted Date  ICMJE September 12, 2018
Results First Posted Date  ICMJE October 9, 2018
Last Update Posted Date November 14, 2018
Actual Study Start Date  ICMJE March 2013
Actual Primary Completion Date November 25, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 12, 2018)
Response Rate (RR) [ Time Frame: Day 29 ]
Response Rate (RR) was determined as the sum of complete response (CR) and partial response (PR). Due to overlap, "complete response rate without platelet recovery" (CRp) is not included in Response Rate (RR). The outcome is reported as the total number without dispersion.
  • CR = No circulating blasts or extramedullary disease; trilineage hematopoiesis; absolute neutrophil count (ANC) > 1,000/microliter; platelets > 100,000/microliter; < 5% blasts in bone marrow.
  • CRp = Meets all criteria for CR except platelet count.
  • PR = Meets all criteria for CR except bone marrow contains 5 to 25% leukemia cells.
Original Primary Outcome Measures  ICMJE
 (submitted: January 14, 2013)
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.
Change History Complete list of historical versions of study NCT01769209 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 12, 2018)
  • Complete Response (CR) [ Time Frame: Day 29 ]
    Complete response (CR) was determined the number of participants who achieved CR by Day 29 after induction treatment. The outcome is reported as the total number without dispersion. CR is defined as:
    • CR = No circulating blasts or extramedullary disease; trilineage hematopoiesis; absolute neutrophil count (ANC) > 1,000/microliter; platelets > 100,000/microliter; < 5% blasts in bone marrow.
    • Not CR = All statuses and conditions if less than or not as defined.
  • Complete Response Without Platelet Recovery (CRp) [ Time Frame: Day 29 ]
    Complete response without platelet recovery (CR) was determined as the number of participants who achieved CRp by Day 29 after induction treatment. The outcome is reported as the total number without dispersion. The outcome reflects only those subjects that meet all complete response (CR) criteria except platelet count; participants that meet all criteria including platelet count are not included in this outcome. CR and CRp are defined below.
    • CR =.No circulating blasts or extramedullary disease; trilineage hematopoiesis; absolute neutrophil count (ANC) > 1,000/microliter; platelets > 100,000/microliter; < 5% blasts in bone marrow.
    • CRp = Meets all criteria for CR except platelet count.
  • Progression-free Survival (PFS) [ Time Frame: 2 years ]
    Progression-free survival (PFS) was assessed as survival without progression at 2 years. The outcome is reported as the number (without dispersion) of the participants alive without progression. Progression = More than 25% increase in circulating and/or bone marrow blasts, or the development of extramedullary disease.
  • Failure-free Survival (FFS) [ Time Frame: 1 year ]
    Failure-free survival (FFS) was assessed as survival without progression or the addition of another systemic therapy, at or within 2 years. The outcome is reported as the number (without dispersion) of the participants alive without progression. Progression is defined below. Progression = More than 25% increase in circulating and/or bone marrow blasts, or the development of extramedullary disease.
  • Overall Survival (OS) [ Time Frame: 2 years ]
    Overall survival (OS) was assessed as participants remaining alive 2 years after induction therapy. The outcome is reported as the number of participants (without dispersion).
  • Related Adverse Events (Grade 3, 4, 5) [ Time Frame: 45 days ]
    Toxicity was assessed as related grade 3, 4, or 5 adverse events (AEs) per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03. The outcome is reported as the total numbers of events (without dispersion) by CTCAE Body System, and whether the event was a hematologic toxicity or non-hematologic toxicity.
  • Induction of Reactive Oxygen Species (ROS) [ Time Frame: 2 years ]
    Circulating acute lymphoblastic leukemia (ALL) blast cells were to be evaluated for the presence of reactive oxygen species (ROS).
Original Secondary Outcome Measures  ICMJE
 (submitted: January 14, 2013)
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Bortezomib and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia
Official Title  ICMJE A Phase II Study of Subcutaneous Bortezomib in Combination With Chemotherapy (VXLD) for Relapsed/Refractory Adult Acute Lymphoblastic Leukemia
Brief Summary This study evaluates the value of bortezomib in combination with specified chemotherapies for the treatment of 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.
Detailed Description

PRIMARY OBJECTIVE:

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:

  • Estimate the rate of complete response (CR) and CR with incomplete platelet recovery (CRp) on Day 29 after re-induction.
  • Determine progression-free survival (PFS) at 2 years after re-induction.
  • Determine failure-free survival (FFS) at 1 year after re-induction.
  • Overall survival (OS) at 1 year after re-induction.
  • Assess safety and tolerability of the study drug.
  • 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 to 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.

Participants are followed up every 3 months for up to 2 years after completion of study treatment.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • B-cell Adult Acute Lymphoblastic Leukemia (ALL)
  • Ph-positive Adult Acute Lymphoblastic Leukemia (ALL)
  • Recurrent Adult Acute Lymphoblastic Leukemia (ALL)
  • T-cell Adult Acute Lymphoblastic Leukemia (ALL)
Intervention  ICMJE
  • Drug: Bortezomib
    Administered subcutaneously (SC) at 1.3 mg/m², on Days 1, 4, 8, and 11.
    Other Names:
    • Velcade
    • LDP 341
    • MLN341
  • Drug: Doxorubicin hydrochloride (HCl)
    Administered intravenously (IV) over 15 min at 60mg/m², on Day 1.
    Other Names:
    • Adriamycin
    • Adriamycin PFS
    • Adriamycin RDF
    • Adria
    • ADM
    • ADR
    • Rubex
    • VXLD
  • Drug: PEG-Asparaginase
    Administered intravenously (IV) or intramuscularly (IM) 2500 U/m² (maximum 3750 U), on Days 5 and 22.
    Other Names:
    • Pegaspargase
    • Oncaspar
    • L-asparaginase with polyethylene glycol
    • Pegasparaginase
    • PEG-L-asparaginase
    • PEG-ASP
  • Drug: Vincristine sulfate
    Administered by intravenous (IV) push at 1.5 mg/m² (maximum 2 mg), on Days 1, 8, 15, and 22.
    Other Names:
    • Leurocristine sulfate
    • Vincasar PFS
    • VCR
  • Drug: Dexamethasone
    Administered orally (PO) at 10 mg/m², daily on Days 1 to 14.
    Other Names:
    • Aeroseb-Dex
    • Decaderm
    • Decadron
    • DM
    • DXM
  • Drug: Cytarabine
    Administered intrathecally (IT) at 100 mg, on Day 1
    Other Names:
    • Cytosine arabinoside
    • ARA-C
    • Arabinofuranosylcytosine
    • Arabinosylcytosine
    • Cytosar-U
  • Drug: Methotrexate
    Administered intrathecally (IT) at 15 mg, on Day 15.
    Other Names:
    • Amethopterin
    • MTX
Study Arms  ICMJE Experimental: Bortezomib + Chemotherapy
Patients receive bortezomib on Days 1, 4, 8, and 11; doxorubicin hydrochloride on Day 1; PEG-asparaginase on Days 5 and 22; vincristine sulfate on Days 1, 8, 15, and 22; dexamethasone daily on Days 1 to 14; cytarabine on Day 1, and methotrexate on Day 15.
Interventions:
  • Drug: Bortezomib
  • Drug: Doxorubicin hydrochloride (HCl)
  • Drug: PEG-Asparaginase
  • Drug: Vincristine sulfate
  • Drug: Dexamethasone
  • Drug: Cytarabine
  • Drug: Methotrexate
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 28, 2017)
18
Original Estimated Enrollment  ICMJE
 (submitted: January 14, 2013)
17
Actual Study Completion Date  ICMJE July 4, 2017
Actual Primary Completion Date November 25, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

INCLUSION CRITERIA

  • Voluntary written informed consent
  • 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 (ie, 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
  • • 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.
  • Has received at least 1 line of prior systemic therapy that may NOT have included bortezomib (Velcade); patients who have undergone autologous/allogeneic stem cell transplantation are eligible
  • Transplant-eligible patients are eligible
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 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 (ULN)
  • Total bilirubin ≤ 1.5 x (ULN unless elevation is deemed due to leukemia infiltration)
  • Adequate renal function defined as creatinine clearance of ≥ 30 mL/minute by the Cockcroft-Gault method

EXCLUSION CRITERIA

  • > 1.5 x ULN total bilirubin
  • ≥ Grade 2 peripheral neuropathy
  • 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
  • Hypersensitivity to bortezomib, boron, or mannitol
  • 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
  • Prior exposure ≥ 350 mg/m² of anthracycline (doxorubicin equivalent)
  • Left ventricular ejection fraction < 40%
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01769209
Other Study ID Numbers  ICMJE IRB-25596
NCI-2012-03094 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
HEMALL0008 ( Other Identifier: OnCore Number )
IRB-25596 ( Other Identifier: Stanford IRB )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Michaela Liedtke, Stanford University
Study Sponsor  ICMJE Stanford University
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Michaela Liedtke, MD Stanford University
PRS Account Stanford University
Verification Date October 2018

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