Clinical Trials /

Combination Chemotherapy and Inotuzumab Ozogamicin in Treating Patients With B Acute Lymphoblastic Leukemia

NCT03488225

Description:

This phase II trial studies how well combination chemotherapy and inotuzumab ozogamicin work in treating patients with B acute lymphoblastic leukemia. Drugs used in chemotherapy, such as cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, dexamethasone, methotrexate and cytarabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as inotuzumab ozogamicin, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving combination chemotherapy and inotuzumab ozogamicin may work better at treating B acute lymphoblastic leukemia.

Related Conditions:
  • B-Cell Acute Lymphoblastic Leukemia
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Hyper-CVAD in Combination With Inotuzumab Ozogamicin as Frontline Therapy for Adults With Acute Lymphocytic Leukemia
  • Official Title: Phase II Study of the Hyper-CVAD Regimen in Sequential Combination With Inotuzumab Ozogamicin as Frontline Therapy for Adults With B-Cell Lineage Acute Lymphocytic Leukemia

Clinical Trial IDs

  • ORG STUDY ID: 2015-0922
  • NCT ID: NCT03488225

Conditions

  • Acute Lymphocytic Leukemia

Interventions

DrugSynonymsArms
CyclophosphamideCytoxan, NeosarHyper-CVAD + Inotuzumab Ozogamicin
MesnaMesnexHyper-CVAD + Inotuzumab Ozogamicin
DoxorubicinDoxorubicin hydrochloride, Adriamycin PFS, Adriamycin RDF, Rubex, AdriamycinHyper-CVAD + Inotuzumab Ozogamicin
VincristineHyper-CVAD + Inotuzumab Ozogamicin
OfatumumabArzerraHyper-CVAD + Inotuzumab Ozogamicin
RituximabRituxanHyper-CVAD + Inotuzumab Ozogamicin
PegfilgrastimNeulasta, PEG-G-CSFHyper-CVAD + Inotuzumab Ozogamicin
FilgrastimG-CSF, NeupogenHyper-CVAD + Inotuzumab Ozogamicin
MethotrexateMTXHyper-CVAD + Inotuzumab Ozogamicin
CytarabineAra-C, Cytosar, DepoCyt, Cytosine arabinosine hydrochlorideHyper-CVAD + Inotuzumab Ozogamicin
CitrovorumLeucovorin, WellcovorinHyper-CVAD + Inotuzumab Ozogamicin
Inotuzumab OzogamicinCMC-544Hyper-CVAD + Inotuzumab Ozogamicin
Mercaptopurine6-MP, 6 Mercaptopurine, PurinetholHyper-CVAD + Inotuzumab Ozogamicin
PrednisoneHyper-CVAD + Inotuzumab Ozogamicin

Purpose

Any time the words "you," "your," "I," or "me" appear, it is meant to apply to the potential participant. The goal of this study is to learn if inotuzumab ozogamicin given in combination with hyper-CVAD can help to control newly diagnosed B-cell acute lymphocytic leukemia (ALL). The safety of this drug combination will also be studied. Hyper-CVAD is a drug combination and schedule that is described below under Intensive Chemotherapy. This is an investigational study. Inotuzumab ozogamicin and hyper-CVAD when given alone are FDA approved and commercially available for the treatment of ALL. Combining inotuzumab ozogamicin with hyper-CVAD is investigational. The study doctor can explain how the study drugs are designed to work. Up to 60 participants will be enrolled in this study. All will take part at MD Anderson.

Detailed Description

      Study Drug Administration Each cycle is 21 days (+/- 7 days).

      Intensive Chemotherapy (Cycles 1 and 3):

      If you are found to be eligible to take part in this study, you will receive hyper-CVAD
      during Cycles 1 and 3 as follows:

        -  On Days 1-3, you will receive cyclophosphamide by vein over 3 hours every 12 hours, for
           a total of 6 doses per cycle.

        -  On Days 1-3, you will receive mesna as a non-stop infusion starting about 1 hour before
           the cyclophosphamide infusion and ending about 12 hours after the last dose of
           cyclophosphamide.

        -  On Days 1-4 and 11-14, you will receive dexamethasone by vein or taken as a tablet by
           mouth.

        -  The doctor will decide if you will receive ofatumumab or rituximab. If you receive
           ofatumumab, you will receive it by vein over about 2 hours (or longer if the doctor
           thinks it is needed) on Days 1, 2, and 11 of Cycle 1 and Days 1 and 11 of Cycle 3. If
           you receive rituximab, you will receive it by vein over about 2 hours (or longer if the
           doctor thinks it is needed) on Days 1 and 11 of Cycles 1 and 3.

        -  On Day 2, you will receive methotrexate intrathecally (through a spinal tap).

        -  On Day 4, you will receive doxorubicin by vein over 24 hours through a central venous
           catheter. A CVC is a sterile flexible tube that will be placed into a large vein while
           you are under local anesthesia. Your doctor will explain this procedure to you in more
           detail, and you will be required to sign a separate consent form for this procedure.

        -  On Days 4 and 11, you will receive vincristine by vein over 1 hour.

        -  On Day 7, you will receive cytarabine intrathecally.

        -  After you complete chemotherapy, you will either receive pegfilgrastim as a one-time
           dose or filgrastim (G-CSF) as an injection under the skin every day until your white
           blood cell counts recover.

      You will receive methotrexate and cytarabine during Cycles 2 and 4 as follows:

        -  On Day 1, you will receive methotrexate by vein over 24 hours.

        -  On Days 2 and 3, you will receive cytarabine over 2 hours by vein every 12 hours, for a
           total of 4 doses per cycle.

        -  Starting on Day 2, you will receive leucovorin by vein 4 times a day for 8 doses per
           cycle.

        -  On Days 1 and 8, you will receive ofatumumab by vein over about 2 hours (or longer if
           the doctor thinks it is needed) or rituximab by vein over about 2 hours (or longer if
           the doctor thinks it is needed).

        -  On Day 5, you will receive cytarabine intrathecally.

        -  On Day 8, you will receive methotrexate intrathecally.

        -  After you complete chemotherapy, you will either receive pegfilgrastim as a one-time
           dose or filgrastim as an injection under the skin every day until your white blood cell
           counts recover.

      During Cycles 5-8: you will receive inotuzumab ozogamicin by vein over about 1 hour on Days 1
      and Day 8 of each cycle.

      Maintenance Therapy:

      Each cycle is 28 days.

      For Cycles 9-20 (12 cycles), you will receive the following drugs:

        -  Three (3) times a day, you will take mercaptopurine tablets by mouth.

        -  One (1) time a week, you will take methotrexate tablets by mouth.

        -  On Day 1 of each cycle, you will receive vincristine by vein over about 1 hour.

        -  On Days 1-5 of each cycle, you will take prednisone tablets by mouth.

      Other Drugs:

      If your doctor thinks it is needed, you may also receive drugs through a spinal tap to help
      lower the risk of the disease coming back in the fluid surrounding your brain.

      You may also be given other drugs to help lower the risk of other side effects (for example,
      you may receive allopurinol, ursodiol, or rasburicase). Your doctor will tell you about these
      drugs, how they will be given, and the possible risks.

      Length of Treatment:

      You may receive up to 20 cycles of study drugs. You will no longer be able to receive the
      study drugs if the disease gets worse, if intolerable side effects occur, if you are unable
      to follow study directions, or if you receive stem cell transplant therapy.

      Your participation on the study will be over after the follow-up bone marrow
      aspirations/biopsies or after the end of the Maintenance Therapy.

      Study Visits:

      Prior to each cycle, you will have a physical exam.

      Once a week during Cycles 1-4, blood (about 2-3 tablespoons) will be drawn for routine tests.

      If the doctor thinks it is needed, you will have a bone marrow aspiration and biopsy on the
      following schedule:

        -  Day 14 of Cycle 1, then 1 time a week for as long as the doctor thinks is needed based
           on the disease status

        -  3 chemotherapy cycles after a complete response in the disease and/or before you start
           inotuzumab ozogamicin

        -  Day 21 of Cycle 5, then after every cycle (exact schedule will depend on the disease
           status at the start of inotuzumab ozogamicin), then every 4 months after that. The study
           staff will let you know when the every 4 month follow-up procedures will stop, and it
           will be based on the disease status.

      Every 4 weeks during Cycles 9-20, blood (about 2-3 tablespoons) will be drawn for routine
      tests.

      At any time, if your doctor thinks it is needed, you will have a CT scan, a PET scan, and/or
      a chest x-ray to check the status of the disease.

      Follow-up:

      Thirty (30) days after you have received your last dose of the inotuzumab ozogamicin, you
      will be called by a member of the study team and asked how you are feeling and about any
      other drugs or treatments you are receiving. The phone call should last about 10 minutes.

      Long-term Follow-up:

      After you have received your last dose of study drugs, you will be called by a member of the
      study team every 6 months. You will be asked how you are feeling and about any other drugs or
      treatments you are receiving. The phone call should last about 10 minutes.
    

Trial Arms

NameTypeDescriptionInterventions
Hyper-CVAD + Inotuzumab OzogamicinExperimentalEach cycle is 21 days. Participants receive Hyper-CVAD during Cycles 1 and 3. Participants receive Methotrexate and Cytarabine during Cycles 2 and 4. On Days 1 and 8, Participants Ofatumumab or Rituximab. Participants receive Inotuzumab Ozogamicin during Cycles 5-8, on Days 1 and Day 8 of each cycle. Cycles 9-20 is maintenance therapy. Each cycle is 28 days. Three (3) times a day, participant takes Mercaptopurine tablets. One (1) time a week, participant takes methotrexate tablets. On Day 1 of each cycle, participant receives vincristine. On Days 1-5 of each cycle, participant takes prednisone tablets.
  • Cyclophosphamide
  • Mesna
  • Doxorubicin
  • Vincristine
  • Ofatumumab
  • Rituximab
  • Pegfilgrastim
  • Filgrastim
  • Methotrexate
  • Cytarabine
  • Citrovorum
  • Inotuzumab Ozogamicin
  • Mercaptopurine
  • Prednisone

Eligibility Criteria

        Inclusion Criteria:

          1. Patients at least 16 years of age with newly diagnosed, previously untreated B-lineage
             ALL, or having achieved CR with one course of induction chemotherapy.

          2. Patients with extramedullary disease only are eligible

          3. Failure to one induction course of chemotherapy (these patients will be analyzed
             separately).

          4. Performance status of 0-3.

          5. Adequate organ function with creatinine less than or equal to 2.0 mg/dL (unless
             considered tumor related), bilirubin less than or equal to 2.0 mg/dL (unless
             considered tumor related).

          6. Adequate cardiac function as assessed by history and physical examination.

          7. No active or co-existing malignancy with life expectancy less than 12 months.

          8. Women of childbearing potential (WOCBP) or male subjects with a partner who is WOCBP
             must agree to use contraception during the study, if sexually active.

        Exclusion Criteria:

          1. Pregnant or nursing women

          2. Known to be HIV-positive

          3. Ph-positive ALL

          4. Active and uncontrolled disease/infection as judged by the treating physician

          5. Unable or unwilling to sign the consent form

          6. Subjects who have current active hepatic or biliary disease (with exception of
             patients with Gilbert's syndrome, asymptomatic gallstones, liver involvement or stable
             chronic liver disease per investigator assessment)

          7. Chronic or current infectious disease requiring systemic antibiotics, antifungal, or
             antiviral treatment such as, but not limited to, chronic renal infection, chronic
             chest infection with bronchiectasis, tuberculosis and active Hepatitis C.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:16 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Event-Free Survival
Time Frame:Start of treatment up to 3 years
Safety Issue:
Description:Event-free survival defined as the time interval from date of treatment start until the date of death, disease progression or relapse.

Secondary Outcome Measures

Measure:Overall Survival
Time Frame:Start of treatment up to 3 years
Safety Issue:
Description:
Measure:Overall Response Rate
Time Frame:Start of treatment up to 3 years
Safety Issue:
Description:
Measure:Minimal Residual Disease (MRD) Negativity Rate
Time Frame:Start of treatment up to two years
Safety Issue:
Description:MRD levels continuously assessed during induction and consolidation therapy by 6-color multiparameter flow. MRD negativity defined by a value of at least 10−4 and confirmed on a second bone marrow aspiration/biopsy performed after a subsequent cycle.
Measure:Adverse Events
Time Frame:Start of treatment up to 30 days after last dose received.
Safety Issue:
Description:NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 utilized for adverse event reporting.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Trial Keywords

  • Acute Lymphocytic Leukemia
  • ALL
  • B-Cell Lineage
  • Cyclophosphamide
  • Cytoxan
  • Neosar
  • Mesna
  • Mesnex
  • Doxorubicin hydrochloride
  • Adriamycin PFS
  • Adriamycin RDF
  • Rubex
  • Adriamycin
  • Doxorubicin
  • Vincristine
  • Ofatumumab
  • Arzerra
  • Rituximab
  • Rituxan
  • Pegfilgrastim
  • Neulasta
  • PEG-G-CSF
  • Filgrastim
  • G-CSF
  • Neupogen
  • Methotrexate
  • Cytarabine
  • Ara-C
  • Cytosar
  • DepoCyt
  • Cytosine arabinosine hydrochloride
  • Citrovorum
  • Leucovorin
  • Wellcovorin
  • Inotuzumab Ozogamicin
  • CMC-544
  • 6-MP 6
  • Mercaptopurine
  • Purinethol
  • MTX
  • Prednisone

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