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

NCT01769209 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: IRB-25596NCI-2012-03094HEMALL0008
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

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)

Outcome Measures

Primary Outcomes (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.

  Day 29

Secondary Outcomes (7)

• Complete Response (CR)

  Day 29

• Complete Response Without Platelet Recovery (CRp)

  Day 29

• Progression-free Survival (PFS)

  2 years

• Failure-free Survival (FFS)

  1 year

• Overall Survival (OS)

  2 years

Study Arms (1)

Bortezomib + Chemotherapy

EXPERIMENTAL

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.

Drug: Bortezomib; Drug: Doxorubicin hydrochloride (HCl); Drug: PEG-Asparaginase; Drug: Vincristine sulfate; Drug: Dexamethasone; Drug: Cytarabine; Drug: Methotrexate

Interventions

Bortezomib DRUG

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

Also known as: Velcade, LDP 341, MLN341

Bortezomib + Chemotherapy

Doxorubicin hydrochloride (HCl) DRUG

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

Also known as: Adriamycin, Adriamycin PFS, Adriamycin RDF, Adria, ADM, ADR, Rubex, VXLD

Bortezomib + Chemotherapy

PEG-Asparaginase DRUG

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

Also known as: Pegaspargase, Oncaspar, L-asparaginase with polyethylene glycol, Pegasparaginase, PEG-L-asparaginase, PEG-ASP

Bortezomib + Chemotherapy

Vincristine sulfate DRUG

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

Also known as: Leurocristine sulfate, Vincasar PFS, VCR

Bortezomib + Chemotherapy

Dexamethasone DRUG

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

Also known as: Aeroseb-Dex, Decaderm, Decadron, DM, DXM

Bortezomib + Chemotherapy

Cytarabine DRUG

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

Also known as: Cytosine arabinoside, ARA-C, Arabinofuranosylcytosine, Arabinosylcytosine, Cytosar-U

Bortezomib + Chemotherapy

Methotrexate DRUG

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

Also known as: Amethopterin, MTX

Bortezomib + Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• \> 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%

Sponsors & Collaborators

• Stanford University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Stanford University, School of Medicine

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Bortezomib; Doxorubicin; pegaspargase; Vincristine; Dexamethasone; Calcium Dobesilate; Cytarabine; Methotrexate

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Aminopterin; Pterins; Pteridines

Results Point of Contact

• Title: Michaela Liedtke, MD
• Organization: Stanford University Medical Center

mliedtke@stanford.edu

650-498-6000

Study Officials

• Michaela Liedtke, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: January 14, 2013
• First Posted: January 16, 2013
• Study Start: March 1, 2013
• Primary Completion: November 25, 2016
• Study Completion: July 4, 2017
• Last Updated: November 14, 2018
• Results First Posted: October 9, 2018

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)