Bortezomib and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia
Condition: 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)
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
Intervention: Bortezomib; Doxorubicin hydrochloride (HCl); PEG-Asparaginase; Vincristine sulfate; Dexamethasone; Cytarabine; Methotrexate
Intervention description: Administered subcutaneously (SC) at 1.3 mg/m², on Days 1, 4, 8, and 11.; Administered intravenously (IV) over 15 min at 60mg/m², on Day 1.; Administered intravenously (IV) or intramuscularly (IM) 2500 U/m² (maximum 3750 U), on Days 5 and 22.; Administered by intravenous (IV) push at 1.5 mg/m² (maximum 2 mg), on Days 1, 8, 15, and 22.; Administered orally (PO) at 10 mg/m², daily on Days 1 to 14.; Administered intrathecally (IT) at 100 mg, on Day 1; Administered intrathecally (IT) at 15 mg, on Day 15.
Intervention MeSH terms: Cytarabine; Dexamethasone; Doxorubicin; Liposomal doxorubicin; Methotrexate; Vincristine; Bortezomib; Asparaginase; Pegaspargase
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

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%