Status:

TERMINATED

Vincristine, Doxorubicin, And Dexamethasone + Ixazomib in Acute Lymphoblastic Leukemia (ALL), Lymphoblastic Lymphoma Or Mixed Phenotype Acute Leukemia

Lead Sponsor:

Ehab L Atallah

Conditions:

Relapsed or Refractory Acute Lymphoblastic Leukemia

Relapsed or Refractory Lymphoblastic Lymphoma

Eligibility:

All Genders

18+ years

Phase:

PHASE1

Brief 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...

Detailed Description

In this phase I study, escalating doses of MLN9708 will be combined with a fixed dose modified VXD regimen. The study drug, MLN9708, will be administered on day 1, 8, and 15. If the patient experience...

Eligibility Criteria

Inclusion

  • 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.

Exclusion

    Key Trial Info

    Start Date :

    June 1 2013

    Trial Type :

    INTERVENTIONAL

    Allocation :

    ACTUAL

    End Date :

    February 29 2016

    Estimated Enrollment :

    5 Patients enrolled

    Trial Details

    Trial ID

    NCT01887587

    Start Date

    June 1 2013

    End Date

    February 29 2016

    Last Update

    January 22 2020

    Active Locations (1)

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    Froedtert Hospital and the Medical College of Wisconsin

    Milwaukee, Wisconsin, United States, 53226