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B-cell Adult Acute Lymphoblastic Leukemia (ALL)Phase 2NCT01769209

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

A Phase 2 study testing Bortezomib, Doxorubicin hydrochloride (HCl) and PEG-Asparaginase in people with B-cell Adult Acute Lymphoblastic Leukemia (ALL) and Ph-positive Adult Acute Lymphoblastic Leukemia (ALL), run by Stanford University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Bortezomib, Doxorubicin hydrochloride (HCl) and PEG-Asparaginase
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteUnited States
Study dates
Mar 2013to 4 Jul 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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

Who cannot join

  • > 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
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  • 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%

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Stanford University, School of Medicine

    Stanford, California, 94305

Other trials in United States

About this study

Official title: A Phase II Study of Subcutaneous Bortezomib in Combination With Chemotherapy (VXLD) for Relapsed/Refractory Adult Acute Lymphoblastic Leukemia

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.

Read the 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.

Being tested
Bortezomib, Doxorubicin hydrochloride (HCl), PEG-Asparaginase, Vincristine sulfate, Dexamethasone
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BortezomibDrug

    Also called Velcade, LDP 341, MLN341

    Administered subcutaneously (SC) at 1.3 mg/m², on Days 1, 4, 8, and 11.

  • Doxorubicin hydrochloride (HCl)Drug

    Also called Adriamycin, Adriamycin PFS, Adriamycin RDF, Adria

    Administered intravenously (IV) over 15 min at 60mg/m², on Day 1.

  • PEG-AsparaginaseDrug

    Also called Pegaspargase, Oncaspar, L-asparaginase with polyethylene glycol, Pegasparaginase

    Administered intravenously (IV) or intramuscularly (IM) 2500 U/m² (maximum 3750 U), on Days 5 and 22.

  • Vincristine sulfateDrug

    Also called Leurocristine sulfate, Vincasar PFS, VCR

    Administered by intravenous (IV) push at 1.5 mg/m² (maximum 2 mg), on Days 1, 8, 15, and 22.

  • DexamethasoneDrug

    Also called Aeroseb-Dex, Decaderm, Decadron, DM

    Administered orally (PO) at 10 mg/m², daily on Days 1 to 14.

  • CytarabineDrug

    Also called Cytosine arabinoside, ARA-C, Arabinofuranosylcytosine, Arabinosylcytosine

    Administered intrathecally (IT) at 100 mg, on Day 1

  • MethotrexateDrug

    Also called Amethopterin, MTX

    Administered intrathecally (IT) at 15 mg, on Day 15.

Study groups in NCT01769209
Study groupRoleWhat they receive
Bortezomib + ChemotherapyExperimentalPatients 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.
Receives: Drug: Bortezomib; Drug: Doxorubicin hydrochloride (HCl); Drug: PEG-Asparaginase; Drug: Vincristine sulfate; Drug: Dexamethasone; Drug: Cytarabine; Drug: Methotrexate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Response Rate (RR)

    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.

    Measured: Day 29

Secondary outcomes (7)

  1. Complete Response (CR)

    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.

    Measured: Day 29

  2. Complete Response Without Platelet Recovery (CRp)

    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.

    Measured: Day 29

  3. Progression-free Survival (PFS)

    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.

    Measured: 2 years

  4. Failure-free Survival (FFS)

    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.

    Measured: 1 year

  5. Overall Survival (OS)

    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).

    Measured: 2 years

  6. Related Adverse Events (Grade 3, 4, 5)

    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.

    Measured: 45 days

  7. Induction of Reactive Oxygen Species (ROS)

    Circulating acute lymphoblastic leukemia (ALL) blast cells were to be evaluated for the presence of reactive oxygen species (ROS).

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jan 2013 (estimated)
  2. Study startMar 2013
  3. Primary completion25 Nov 2016
  4. Study completion4 Jul 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01769209
Sponsor's protocol ID
IRB-25596
Other IDs
NCI-2012-03094, HEMALL0008, IRB-25596
Status last verified
Oct 2018
First submitted
14 Jan 2013
Last updated
14 Nov 2018
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bortezomib, Doxorubicin hydrochloride (HCl) and PEG-Asparaginase in people with B-cell Adult Acute Lymphoblastic Leukemia (ALL) and Ph-positive Adult Acute Lymphoblastic Leukemia (ALL), run by Stanford University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Oct 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Response Rate (RR) (time frame: Day 29). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01769209.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2018.

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