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

NCT ID: NCT01769209

Last Updated: 2018-11-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-31
• Study Completion Date: 2017-07-04

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.

Conditions

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)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Bortezomib

Intervention Type: DRUG

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

Doxorubicin hydrochloride (HCl)

Intervention Type: DRUG

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

PEG-Asparaginase

Intervention Type: DRUG

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

Vincristine sulfate

Intervention Type: DRUG

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

Dexamethasone

Intervention Type: DRUG

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

Cytarabine

Intervention Type: DRUG

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

Methotrexate

Intervention Type: DRUG

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

Interventions

Bortezomib

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

Intervention Type: DRUG

Doxorubicin hydrochloride (HCl)

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

Intervention Type: DRUG

PEG-Asparaginase

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

Intervention Type: DRUG

Vincristine sulfate

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

Intervention Type: DRUG

Dexamethasone

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

Intervention Type: DRUG

Cytarabine

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

Intervention Type: DRUG

Methotrexate

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

Intervention Type: DRUG

Other Intervention Names

Velcade; LDP 341; MLN341; Adriamycin; Adriamycin PFS; Adriamycin RDF; Adria; ADM; ADR; Rubex; VXLD; Pegaspargase; Oncaspar; L-asparaginase with polyethylene glycol; Pegasparaginase; PEG-L-asparaginase; PEG-ASP; Leurocristine sulfate; Vincasar PFS; VCR; Aeroseb-Dex; Decaderm; Decadron; DM; DXM; Cytosine arabinoside; ARA-C; Arabinofuranosylcytosine; Arabinosylcytosine; Cytosar-U; Amethopterin; MTX

Eligibility Criteria

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%

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Michaela Liedtke

Assistant Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michaela Liedtke, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University, School of Medicine

Stanford, California, United States

Countries

United States

Other Identifiers

NCI-2012-03094

Identifier Type: REGISTRY

Identifier Source: secondary_id

HEMALL0008

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-25596

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-25596

Identifier Type: -

Identifier Source: org_study_id