Clinical Trials /

Phase I Study of MLN 9708 in Addition to Chemotherapy for the Treatment of Acute Lymphoblastic Leukemia in Older Adults

NCT02228772

Description:

This research study is evaluating a combination of drugs considered standard treatment for children and young adults with acute lymphoblastic leukemia (ALL), in combination with a new drug called MLN 9708. Additionally, the study is also evaluating if bone marrow or stem cell transplantation, which will be given to some participants, helps to prevent ALL from returning.

Related Conditions:
  • Acute Lymphoblastic Leukemia
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Phase I Study of <span class="go-doc-concept go-doc-intervention">MLN 9708</span> in Addition to <span class="go-doc-concept go-doc-intervention">Chemotherapy</span> for the Treatment of <span class="go-doc-concept go-doc-disease">Acute Lymphoblastic Leukemia</span> in Older Adults

Title

  • Brief Title: Phase I Study of MLN 9708 in Addition to Chemotherapy for the Treatment of Acute Lymphoblastic Leukemia in Older Adults
  • Official Title: Phase I Study of MLN 9708 in Addition to Chemotherapy for the Treatment of Acute Lymphoblastic Leukemia in Older Adults
  • Clinical Trial IDs

    NCT ID: NCT02228772

    ORG ID: 14-200

    Trial Conditions

    Acute Lymphoblastic Leukemia

    Lymphoblastic Lymphoma

    B-cell Adult Acute Lymphoblastic Leukemia

    T-cell Adult Acute Lymphoblastic Leukemia

    Trial Interventions

    Drug Synonyms Arms
    MLN 9708 Ixazomib MLN 9708
    Vincristine Oncovin, Vincasar PFS, Vincrex, Vincristine sulfate, VCR MLN 9708
    Cytarabine Ara-C, Cytosar-U, Cytosine arabinoside MLN 9708
    Doxorubicin Adriamycin, Rubex MLN 9708
    Mercaptopurine 6-MP, Purinethol, Purixan MLN 9708
    Cyclophosphamide Cytoxan, Neosar, CTX MLN 9708
    Methotrexate Folex, Mexate, MTX, Methotrex (formerly Amethopterin) MLN 9708

    Trial Purpose

    This research study is evaluating a combination of drugs considered standard treatment for
    children and young adults with acute lymphoblastic leukemia (ALL), in combination with a new
    drug called MLN 9708. Additionally, the study is also evaluating if bone marrow or stem cell
    transplantation, which will be given to some participants, helps to prevent ALL from
    returning.

    Detailed Description

    In this research study, the investigators are studying the optimal dose of the drug MLN 9708
    when given with a standard multi-drug regimen. In the first part of the study, up to 18
    participants will be enrolled at different doses of MLN 9708. Once the maximally tolerated
    (highest, safest dose) is established, an additional 10 participants will be enrolled.

    Additionally, bone marrow (tissue found in the inside of bones) or stem cell transplantation
    will be given to some participants to study whether it helps to prevent ALL from returning.

    The study treatment consists of several different stages

    - Induction

    - Consolidation 1

    - Or Stem Cell or Bone Marrow Transplant (if you are eligible based on your medical
    condition and the availability of a matched stem cell donor)

    - Or If you do not have a transplant:

    - CNS Therapy

    - Consolidation 2

    - Continuation Therapy

    Trial Arms

    Name Type Description Interventions
    MLN 9708 Experimental Dose escalation will occur using a standard 3+3 dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation and de-escalation. MLN 9708 will be given with standard multi-drug regimen for ALL . MLN 9708 will be administered on determined days during Induction therapy cycle and Consolidation cycle. If remission occurs and if eligible, the next stage with be either Stem Cell or Bone Marrow Transplant. If not eligible to receive a transplant, the participant will continue on this study for the next 3 stages. CNS Therapy Consolidation 2 Continuation Therapy No further MLN9708, the investigational drug, will be given after Consolidation 1 Standard chemotherapy -Vincristine, Cytarabine, Doxorubicin, Mercaptopurine, Cyclophosphamide, Methotrexate MLN 9708, Vincristine, Cytarabine, Doxorubicin, Mercaptopurine, Cyclophosphamide, Methotrexate

    Eligibility Criteria

    Inclusion Criteria:

    - Acute lymphoblastic leukemia, excluding known mature B-cell ALL by the presence of
    any of the following: surface immunoglobulin, L3 morphology, t(8;14)(q24;q32),
    t(8;22), or t(2;8).

    - Patients with mature B-cell ALL will be removed from the protocol as soon as that
    diagnosis is made and should be treated on a B-cell leukemia (Burkitt's) protocol.
    NOTE: Patients with T-cell surface markers and a t(8;14)(q24;q11) remain eligible.

    - Patients with lymphoblastic lymphoma are also eligible

    - No prior anti-leukemic therapy except the following are allowed: <1 week of
    corticosteroids, or hydroxyurea or emergent leukopheresis. Longer steroid use for
    diseases other than leukemia is permitted.

    - Age 51- 75 years

    - Voluntary written consent must be given before performance of any study-related
    procedures not part of standard medical care, with the understanding that consent may
    be withdrawn by the patient at any time without prejudice to future medical care.

    - If patient is known to be HIV positive, they will not be eligible for the protocol.
    HIV testing is not mandatory prior to protocol enrollment.

    - Patients whose comorbid medical condition, in the investigator's opinion, would make
    participation in this trial and adherence to the protocol guidelines difficult should
    be excluded.

    - Patients with an active psychiatric or mental illness making informed consent or
    careful clinical follow-up unlikely are excluded.

    - Ejection fraction 45%

    - Creatinine<2.0 times upper limit of normal

    - Total bilirubin < 1.5 times upper limit of normal except for known conjugation
    diseases such as Gilbert's, ALT and AST <3.0 times upper limit of normal. Direct
    bilirubin is not an inclusion criteria.

    - ECOG performance status of 0, 1, 2

    - Non pregnant and non lactating 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, AND

    - Must also adhere to the guidelines of any treatment-specific pregnancy
    prevention program, if applicable, 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 (i.e., 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

    - Must also adhere to the guidelines of any treatment-specific pregnancy
    prevention program, if applicable, 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.

    - Female patients who are lactating or have a positive serum pregnancy test during the
    screening period.

    - Major surgery within 14 days before enrollment. Biopsies and line placement
    procedures are not exclusion criteria.

    - Radiotherapy within 14 days before enrollment. Radiotherapy is excluded during
    induction and consolidation 1 while receiving MLN 9708.

    - Evidence of current uncontrolled cardiovascular conditions, including uncontrolled
    hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure,
    unstable angina, or myocardial infarction within the past 6 months.

    - Active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV)
    positive. Hepatitis and HIV testing are not required prior to the start of treatment.

    - Any serious medical or psychiatric illness that could, in the investigator's opinion,
    potentially interfere with the completion of treatment according to this protocol.

    - Known allergy to any of the study medications, their analogues, or excipients in the
    various formulations of any agent.

    - Patient has Grade 3 peripheral neuropathy, or Grade 2 with pain on clinical
    examination during the screening period.

    - Known GI disease or GI procedure that could interfere with the oral absorption or
    tolerance of MLN9708 including difficulty swallowing.

    - 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.

    - Participation in other clinical trials, including those with other investigational
    agents not included in this trial, within 21days of the start of this trial and
    throughout induction and consolidation 1 portions of this trial (while on MLN 9708).
    Patients may enroll in transplant and post transplant studies after consolidation 1
    treatment (See Section 6.5).

    - Systemic treatment, within 14 days before the first dose of MLN9708, with strong
    inhibitors of CYP1A2 (fluvoxamine, enoxacin), strong inhibitors of CYP3A
    (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.
    Ciprofloxocin should not be administered for at least 2 days before MLN 9708
    administration. Extended release ciprofloxocin should not be administered for at
    least 3 days prior to MLN 9708 administration.

    Minimum Eligible Age: 51 Years

    Maximum Eligible Age: 75 Years

    Eligible Gender: Both

    Primary Outcome Measures

    Maximum Dose Tolerated of MLN 9708

    Secondary Outcome Measures

    Percentage of Patient with Complete Remission (CR) rate at the end of induction therapy

    Percentage of Participants with Disease Free Survival

    Rate of Overall survival (OS)

    Complete Remission Rate

    Rate of Toxicity

    Trial Keywords

    Acute lymphoblastic Leukemia

    Lymphoblastic lymphoma

    B-cell Adult Acute Lymphoblastic Leukemia

    T-cell Adult Acute Lymphoblastic Leukemia