Trial record 5 of 1363 for:    "Acute lymphoblastic leukemia"

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Stanford University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Michaela Liedtke, Stanford University
ClinicalTrials.gov Identifier:
NCT01769209
First received: January 14, 2013
Last updated: July 13, 2014
Last verified: July 2014
  Purpose

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. Drugs used in chemotherapy, such as doxorubicin hydrochloride, vincristine sulfate, pegaspargase, dexamethasone, and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with combination chemotherapy may be an effective treatment for acute lymphoblastic leukemia


Condition Intervention Phase
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
Drug: doxorubicin hydrochloride
Drug: pegaspargase
Drug: vincristine sulfate
Drug: dexamethasone
Drug: cytarabine
Drug: methotrexate
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Subcutaneous Bortezomib in Combination With Chemotherapy in Relapsed/Refractory Adult Acute Lymphoblastic Leukemia

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • CR rate [ Time Frame: On day 29 at the end of induction therapy ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: From the start of treatment to disease progression or death, whichever comes first, assessed up to 2 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Compared to a historical baseline.

  • Failure-free survival (FFS) [ Time Frame: At 1 year ] [ Designated as safety issue: No ]
    Analyzed by the Kaplan Meier method. Compared to a historical baseline.

  • Survival percent [ Time Frame: At 1 year ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 17
Study Start Date: March 2013
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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%
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01769209

Locations
United States, California
Stanford University Recruiting
Stanford, California, United States, 94305
Contact: Ying Hao, PhD    650-723-0646    yhao@stanford.edu   
Principal Investigator: Michaela Liedtke         
Sponsors and Collaborators
Stanford University
Investigators
Principal Investigator: Michaela Liedtke Stanford University
  More Information

No publications provided

Responsible Party: Michaela Liedtke, Assistant Professor of Medicine, Stanford University
ClinicalTrials.gov Identifier: NCT01769209     History of Changes
Other Study ID Numbers: HEMALL0008, NCI-2012-03094
Study First Received: January 14, 2013
Last Updated: July 13, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Pegaspargase
Bortezomib
Asparaginase
Cytarabine
Dexamethasone
Doxorubicin
Methotrexate
Vincristine
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on July 28, 2014