Vincristine, Doxorubicin, And Dexamethasone + Ixazomib in Acute Lymphoblastic Leukemia (ALL), Lymphoblastic Lymphoma Or Mixed Phenotype Acute Leukemia
Condition: Relapsed or Refractory Acute Lymphoblastic Leukemia; Relapsed or Refractory Lymphoblastic Lymphoma; Mixed Phenotype Acute Leukemia
MeSH terms: Lymphoma; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Lymphoma, Non-Hodgkin; Acute Disease
Intervention: MLN9708; Vincristine; Doxorubicin; Dexamethasone
Intervention MeSH terms: Dexamethasone; Doxorubicin; Vincristine; Ixazomib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a phase I study of vincristine, doxorubicin and dexamethasone (modified VXD) plus
      MLN9708 in adults with relapsed or refractory acute lymphoblastic leukemia/lymphoma,
      lymphoblastic lymphoma or mixed phenotype acute leukemia.
    

Eligibility criteria:

        Each patient must meet all of the following inclusion criteria to be enrolled in the study:

        Inclusion

          -  Male or female patients 18 years or older

          -  Have relapsed B or T-precursor acute lymphocytic leukemia/lymphoma, lymphoblastic
             lymphoma or mixed phenotype acute leukemia with increased bone marrow or peripheral
             blood blasts by morphology with or without CNS involvement

          -  Prior therapy: At least two prior treatment attempts to induce remission with no limit
             on the number of prior treatment regimens.

          -  Patients are eligible after allogeneic stem cell transplantation

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2

          -  Patients must meet the following clinical laboratory criteria:

               -  Total bilirubin ≤ 1.5 x the upper limit of the normal range (ULN).

               -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN.

               -  Calculated creatinine clearance ≥ 30 mL/min

               -  Absolute neutrophil count (ANC) > 1,000/cmm and platelets > 75,000/cmm unless the
                  cytopenias are secondary to disease

          -  Life expectancy reasonably adequate for evaluating the treatment effect

          -  Patients must be at least 2 weeks from major surgery, radiation therapy, participation
             in other investigational trials and have recovered from clinically significant
             toxicities of these prior treatments

          -  Female patients 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 90 days after the last dose of study drug, OR

               -  Agree to practice true abstinence when this is in line with the preferred and
                  usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation,
                  symptothermal, post-ovulation methods] and withdrawal are not acceptable methods
                  of contraception.)

          -  Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree
             to one of the following:

               -  Agree to practice effective barrier contraception during the entire study
                  treatment period and through 90 days after the last dose of study drug, OR

               -  Agree to practice true abstinence when this is in line with the preferred and
                  usual lifestyle of the subject. (Periodic abstinence (eg, calendar, ovulation,
                  symptothermal, post-ovulation methods] and withdrawal are not acceptable methods
                  of contraception.).

        Exclusion Criteria:

        Patients meeting any of the following exclusion criteria are not to be enrolled in the
        study:

          -  Patients who are Ph+ ALL who are naive to therapy with an approved tyrosine kinase
             inhibitor.

          -  Prior exposure to ≥350 mg/m2 of anthracycline (in doxorubicin equivalent dosing), or
             left ventricular fractional shortening less than 50%.

          -  Failure to have fully recovered (ie, ≤ Grade 2 toxicity) from the effects of prior
             chemotherapy regardless of the interval since last treatment.

          -  Major surgery within 14 days before enrollment.

          -  Chemotherapy in the last 14 days. (Steroids or Intrathecal chemotherapy will be
             allowed).

          -  Systemic treatment, within 7 days before study enrollment, with strong inhibitors of
             cytochrome P450 1A2 (CYP1A2) (e.g., fluvoxamine, enoxacin, ciprofloxacin), strong
             inhibitors of cytochrome P4503A (CYP3A) (e.g., clarithromycin, telithromycin,
             itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A
             inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital),
             or use of Ginkgo biloba or St. John's wort.

          -  Uncontrolled intercurrent illness including, but not limited to ongoing or active
             infection, symptomatic congestive heart failure, or psychiatric illness/social
             situations that would limit compliance with study requirements. Patients receiving
             intravenous antibiotics for infections that are under control may be included in this
             study.

          -  Known allergy to any of the study medications, their analogues, or excipients in the
             various formulations of any agent.

          -  Inability to swallow oral medication, inability or unwillingness to comply with the
             drug administration requirements, or GI procedure that could interfere with the oral
             absorption or tolerance of treatment.

          -  Diagnosed or treated for another malignancy within 2 years before study enrollment or
             previously diagnosed with another malignancy and have any evidence of residual
             disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are
             not excluded if they have undergone complete resection.

          -  Patient has ≥ Grade 2 peripheral neuropathy.

          -  Participation in clinical trials with other investigational agents not included in
             this trial, within 14 days of the start of this trial and throughout the duration of
             this trial.

          -  Female patients who are breastfeeding or have a positive serum pregnancy test during
             the screening period or a positive urine pregnancy test on Day 1 before first dose of
             study drug.