Clinical Trials /

Combination Chemotherapy and Nelarabine in Treating Patients With T-cell Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

NCT00501826

Description:

This phase II trial studies the side effects and how well combination chemotherapy and nelarabine work in treating patients with T-cell acute lymphoblastic leukemia or lymphoblastic lymphoma. Drugs used in chemotherapy, such as cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, dexamethasone, methotrexate, cytarabine, mercaptopurine, prednisone, pegaspargase, nelarabine, and venetoclax work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Related Conditions:
  • Adult T-Cell Acute Lymphoblastic Leukemia
  • T-Cell Lymphoblastic Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Hyper-CVAD Plus Nelarabine in Untreated T-ALL/Lymphoblastic Lymphoma
  • Official Title: Phase II Study of Hyper-CVAD Plus Nelarabine in Previously Untreated T-ALL and Lymphoblastic Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: 2006-0328
  • SECONDARY ID: NCI-2012-01518
  • NCT ID: NCT00501826

Conditions

  • Leukemia
  • Lymphoblastic Lymphoma
  • Leukemia, Lymphoblastic, Acute

Interventions

DrugSynonymsArms
DoxorubicinAdriamycin, RubexHyper-CVAD + Nelarabine
CyclophosphamideNeosar, CytoxanHyper-CVAD + Nelarabine
CytarabineAra-C, Cytosar, DepoCyt, Cytosine Arabinosine HydrochlorideHyper-CVAD + Nelarabine
DexamethasoneDecadronHyper-CVAD + Nelarabine
MethotrexateHyper-CVAD + Nelarabine
VincristineHyper-CVAD + Nelarabine
NelarabineArranonHyper-CVAD + Nelarabine

Purpose

The goal of this clinical research study is to learn the effectiveness of intensive chemotherapy given in combination with nelarabine (followed by maintenance therapy) in the treatment of patients with T cel ALL and T cell lymphoblastic lymphoma. The safety of this treatment will also be studied.

Detailed Description

      The intensive chemotherapy (hyper-CVAD therapy) used in this study includes a combination of
      7 chemotherapy drugs. These drugs include Adriamycin (doxorubicin), cyclophosphamide,
      cytarabine (Ara-C), dexamethasone, methotrexate, nelarabine, and vincristine.

      The maintenance therapy used in this study includes a combination of 5 chemotherapy drugs.
      These drugs include pegaspargase, methotrexate, prednisone, 6-mercaptopurine, and
      vincristine.

      Ara-C is designed to insert itself into DNA (the genetic material of cells) and stop the DNA
      from repairing itself.

      Cyclophosphamide is designed to interfere with the multiplication of cancer cells, which may
      slow or stop their growth and spread throughout the body. This may cause the cancer cells to
      die.

      Dexamethasone, doxorubicin, methotrexate, prednisone, and 6-mercaptopurine are each designed
      to stop or slow the growth of cancer cells, which may cause the cells to die.

      Nelarabine is designed to inhibit ("turn off") the growth and division of cancer cells.

      Vincristine is designed to interfere with the multiplication of cancer cells, which may slow
      or stop their growth and spread throughout the body. This may cause the cancer cells to die.

      If you are found to be eligible to take part in this study, you will receive 2 kinds of
      intensive chemotherapy regimens (hyper-CVAD therapy and methotrexate plus Ara-C) that will
      alternate for a total of 8 courses (4 courses each). One (1) course of therapy is between 21
      and 28 days. All chemotherapy will be given through a large vein by a central venous
      catheter. A central venous catheter 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.

      Intensive Chemotherapy:

      Hyper-CVAD therapy will be given during Courses 1, 3, 5, and 7. For this therapy, you will
      receive cyclophosphamide by vein over 2-3 hours every 12 hours for a total of 6 doses. It
      will be given over 3 days (Days 1, 2, and 3). You will receive doxorubicin by vein over 24
      hours on Day 4. The doxorubicin infusion may be extended up to 48 hours, if you are
      considered to have poor heart function (provided this is known) because you may tolerate
      this drug better as a slow continuous infusion. You will receive vincristine by vein over
      15-30 minutes on Days 4 and 11. You will receive dexamethasone 1 time a day by mouth or by
      vein over a few minutes on Days 1-4 and Days 11-14. You will also receive G-CSF (Filgrastim)
      by vein over a few minutes or just under the skin starting about 24-72 hours after the
      completion of each course of chemotherapy and until your white blood cell count has
      recovered (which will help with rapid recovery of normal bone marrow). You may receive
      pegfilgrastim given as one dose under the skin rather than filgrastim.

      For participants 60 years or older, this first course of chemotherapy will be given in a
      protective isolation room for monitoring by study staff to help watch for and decrease the
      risk of infections.

      Methotrexate will be given in combination with Ara-C during Courses 2, 4, 6, and 8. You will
      receive methotrexate by vein over 24 hours on Day 1. You will receive Ara-C by vein on Days
      2-3, over 2-3 hours every 12 hours for a total of 4 doses. Doses of Ara-C will be adjusted
      according to the level of methotrexate you receive. Blood (about 1 teaspoon) will be drawn
      to measure the study drug level. Leucovorin, used to help decrease the side effects of
      methotrexate, will be given by vein (over 15 minutes) or by mouth (every 6 hours) for 2-3
      days (or until the blood level of methotrexate is low enough to stop leucovorin). Filgrastim
      will be given at the same dose and schedule as during Courses 1, 3, 5, and 7. You may
      receive pegfilgrastim given as one dose under the skin rather than filgrastim.

      During treatment, you will have a physical exam, including measurement of your vital signs.
      You will have blood drawn (about 1 tablespoon each) at least once a week and sometimes up to
      3 times a week. After 1 or 2 courses of chemotherapy, the tests done during the screening
      visit will be repeated to check for disease response to treatment. A bone marrow biopsy will
      be repeated starting at 2 weeks into therapy. This biopsy will be repeated about every week
      until the disease response to treatment is known.

      If the leukemia or lymphoma is responding to therapy and you have not experienced any
      intolerable side effects, you will continue on therapy for up to 8 courses. You will be
      taken off this study if the disease gets worse or you experience any intolerable side
      effects.

      To decrease the risk that leukemia will develop in the brain, you will be given treatment to
      the brain by an injection into your spinal fluid with methotrexate around Day 2. Ara-C will
      be given by an injection into your spinal fluid on about Day 7 of the course. The total
      number of these treatments may be up to 8, which means that you will have 2 with each course
      until the total number of these treatments is reached. During Courses when you receive
      nelarabine, injections into your spinal fluid will be given later (around Days 15 and 22 of
      each course). An Ommaya reservoir may also be surgically placed as a route to treat leukemia
      in the brain or to decrease the risk of leukemia in the brain. It would be placed in
      participants who have difficulty with the spinal treatments. An Ommaya reservoir is a tube
      inserted under the skin of the scalp that enters into the spinal fluid cavity of the brain.

      After the first 4 courses, you will receive 1 course of nelarabine. Nelarabine will be given
      by vein over 2 hours once a day for 5 days. After about 21-35 days, you will continue with
      Course 5 (Hyper-CVAD). After Course 5, you will receive a second course of nelarabine at the
      same dose and schedule as before. Once this course is complete, you will continue with
      Course 6 (methotrexate and cytarabine).

      After completion of the treatment, you will have a complete physical exam, including
      measurement of your vital signs. You will have blood drawn (about 8 teaspoons) for routine
      tests. You will have a chest x-ray or CT scans performed, if needed. You may have a bone
      marrow biopsy repeated. If you had enlarged lymph glands in the center of the chest, you may
      receive radiation to the chest. If you do not need radiation, you will proceed with monthly
      maintenance chemotherapy. If you did require radiation (based on what your doctor thinks is
      best), you will start maintenance chemotherapy after finishing radiation.

      Maintenance Therapy:

      Maintenance chemotherapy will be given for a total of 30 months and will be interrupted by 2
      periods of intensive chemotherapy courses. For maintenance therapy, you will receive
      6-mercaptopurine by mouth up to 3 times a day, methotrexate by mouth once a week,
      vincristine by vein once a month over a few minutes, and prednisone by mouth once a day for
      5 days in a row every month. The first period of intensive chemotherapy courses will be
      given at Courses 6 and 7 into the maintenance program. For the intensive chemotherapy at
      this time, you will receive nelarabine by vein over 2 hours once a day for 5 days in a row
      for about 21-35 days apart from each other. The second period of intensive chemotherapy
      courses will be given at Courses 18 and 19. It will start first with methotrexate by vein on
      Day 1 and pegaspargase by vein on Day 2. These will be given once a week for 4 doses. The
      following month, you will receive hyper-CVAD (like during Course 1 at the very beginning of
      treatment). The hyper-CVAD may begin before the combination of methotrexate and
      pegaspargase.

      Intensive chemotherapy will be given on an inpatient or outpatient basis (depending on what
      the study doctor thinks is safe) for the 8 intensive cycles of chemotherapy. The maintenance
      treatments may be given on an outpatient basis. However, under some circumstances (such as
      intolerance to intensive chemotherapy), you may be moved from the intensive chemotherapy to
      the maintenance phase before the completion of 8 cycles of intensive chemotherapy or without
      having received nelarabine.

      After completion of all therapy, you will return every 3-6 months for a checkup. You may
      have x-rays repeated, if needed. If you have a complete remission, you will have bone marrow
      biopsies repeated about every 4 months to evaluate the marrow for "minimal residual
      disease," which is the presence or absence of very small amounts of leukemia that cannot be
      usually detected by routine blood tests.

      This is an investigational study. All of the drugs used in this study are FDA approved and
      commercially available. Their use together in this study is investigational and for use in
      research only. Up to 100 patients will take part in this study. All will be enrolled at MD
      Anderson.
    

Trial Arms

NameTypeDescriptionInterventions
Hyper-CVAD + NelarabineExperimentalIntensive chemotherapy (hyper-CVAD therapy) includes combination of 7 chemotherapy drugs: Adriamycin (doxorubicin), cyclophosphamide, cytarabine (Ara-C), dexamethasone, methotrexate, nelarabine, and vincristine.
  • Doxorubicin
  • Cyclophosphamide
  • Cytarabine
  • Dexamethasone
  • Methotrexate
  • Vincristine
  • Nelarabine

Eligibility Criteria

        Inclusion Criteria:

          1. Previously untreated T cell ALL including T cell lymphoblastic lymphoma. Failure to
             one induction course of chemotherapy are eligible. Patients in CR after </= 2 courses
             are also eligible.

          2. ECOG performance status less than or equal to 3.

          3. Serum bilirubin less than or equal to 2.0 mg/dL unless considered due to involvement
             by tumor when an upper limit of 5.0 mg/dL is acceptable. SGOT or SGPT less than or
             equal to 4 x ULN.

          4. Serum creatinine less than or equal to 2.0 mg/dL unless considered due to involvement
             by tumor when an upper limit of 2.5 mg/dL is acceptable.

        Exclusion Criteria:

        1) Pregnant or nursing women
      
Maximum Eligible Age:N/A
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete Remission (CR) Rate
Time Frame:3 Years
Safety Issue:
Description:Complete remission (CR) defined as normalization of peripheral blood and bone marrow with 5% or less blasts in a normocellular or hypercellular marrow with a granulocyte count of 1 x 109/L or above and a platelet count of 100 x 109/L or above. Complete resolution of all sites of extramedullary disease is required for CR. Remission interval is dated from end of the 4-week normalization period that defines CR, and assessed by methods of Kaplan and Meier.

Details

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

Trial Keywords

  • Leukemia
  • ALL
  • T-cell ALL
  • Lymphoblastic Lymphoma
  • Hyper-CVAD
  • Doxorubicin
  • Cyclophosphamide
  • Cytarabine
  • Dexamethasone
  • Methotrexate
  • Vincristine
  • Nelarabine

Last Updated

March 23, 2017