Augmented Berlin-Frankfurt-Munster (BFM) Therapy for Adolescent/Young Adults With Acute Lymphoblastic Leukemia or Acute Lymphoblastic Lymphoma
Condition: Lymphoblastic Leukemia; Lymphoblastic Lymphoma
MeSH terms: Lymphoma; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Lymphoma, Non-Hodgkin
Study type: Interventional
Phase: Phase 2

Summary: 
      Objectives:

      A. Primary objective:

      1 To assess the feasibility and the effectiveness of pediatric type therapy (augmented BFM)
      in patients age 12 through 40 with untreated precursor-B or T acute lymphoblastic leukemia
      (ALL) or lymphoblastic lymphoma (LL).

      B. Secondary objective:

        1. To evaluate the prognostic significance of minimal residual disease in bone marrow
           samples at the end of induction and at the end of consolidation in this group of
           patients.

        2. To prospectively evaluate gene hypermethylation status in this group of patients.

        3. To prospectively analyze asparaginase activity and anti-asparaginase antibody formation
           in this population of patients.
    

Detailed description: 
      Induction:

      During Induction, you will receive augmented Berlin-Frankfurt-Munster chemotherapy, which is
      made up of a combination of Cerubidine®, Daunorubicin Hydrochloride (daunorubicin), Oncovin®
      (vincristine), prednisone, dexamethasone, Oncaspar® (PEG Asparaginase), and MTX amethopterin
      (methotrexate). All of these drugs are designed to interfere with the multiplication of
      cancer cells to cause them to die and to keep the cancer from coming back.

      If you are found to be eligible to take part in this study, on Day 1 or during the spinal tap
      procedure, you will be given cytarabine as an injection in your spinal fluid. Within 3 days,
      you will begin the Induction course, which will last for 4 weeks.

      Daunorubicin and vincristine will be given through a needle in your vein on Days 1, 8,15, and
      22. During the first week of therapy, you will be given 1 infusion of PEG Asparaginase by
      vein. You will take prednisone by mouth on Days 1-28. Methotrexate will be injected into your
      spinal fluid on Weeks 2 and 5 during your spinal tap. Cerebrospinal fluid (CSF) studies will
      be sent with each spinal tap to test the fluid for leukemia. If there is disease in your
      spinal fluid before starting the treatment, you will be given additional methotrexate doses
      once a week until there is no disease present. You will continue to receive methotrexate in
      spinal taps every other week for 8 doses, then monthly for 6 doses.

      Blood (about 3 teaspoons) will be drawn multiple times during the study for routine tests.
      You will have a bone marrow aspirate or biopsy on Days 15 and 29 and then as needed to
      confirm remission.

      If you have less than 5% immature cells in the bone marrow, 1 week after Induction, you will
      continue treatment with Consolidation 1. If you achieved remission after 4 weeks of Induction
      treatment, you will then have treatment with Consolidation 1, which will be discussed in a
      separate informed consent document.

      If you have LL and had no bone marrow involvement at screening, you will have a chest x-ray,
      CT scans, and PET scans to measure the disease. Consolidation 1 and other phases of
      chemotherapy will be discussed in a separate informed consent document.

      If you still have more than 5% leukemia cells in the bone marrow after Induction therapy, you
      will receive 2 extra weeks of therapy called "Extended Induction" before going to the next
      phase of therapy. You will receive daunorubicin by vein on Day 1. You will receive
      vincristine on Weeks 1 and 2 by vein. You will take prednisone by mouth on Days 1-14. You
      will receive PEG Asparaginase by vein in the first week of the Extended Induction. Blood
      (about 3 teaspoons) will be drawn weekly during the Extended Induction period for routine
      tests.

      At the end of the Extended Induction period, you will have a physical exam and a bone marrow
      aspirate or biopsy to learn your response to treatment.

      After Extended Induction, if the disease is in remission, then you will have 1 course of
      Consolidation 1, 2 courses of Consolidation 2, and 2 courses of Consolidation 3 before
      proceeding to Maintenance therapy. A separate discussion and informed consent document for
      Consolidation and Maintenance will be provided.

      Length of Study:

      You may remain on study for as long as you are benefiting. However, if after Extended
      Induction, the disease is not in remission, you will be taken off study, and your doctor will
      discuss other treatment options with you.

      You may be taken off study if the disease gets worse or comes back during treatment,
      intolerable side effects occur, new information becomes available to your study doctor, if
      your doctor thinks it is in your best interest, or if you do not attend your appointments,
      which are scheduled at least once every 3 months.

      This is an investigational study. The chemotherapy drugs used in this study are FDA approved
      and commercially available. Up to 125 patients will take part in this study. All will be
      enrolled at MD Anderson.

      Consolidation and Maintenance:

      During Consolidation, you will receive cyclophosphamide, cytarabine, 6-mercaptopurine,
      vincristine, PEG asparaginase, methotrexate, doxorubicin, 6-thioguanine, and dexamethasone.
      During Maintenance, you will receive, vincristine, dexamethasone, 6-mercaptopurine, and
      methotrexate. All of these drugs are designed to interfere with the multiplication of cancer
      cells to cause them to die and to keep the cancer from coming back.

      If you achieved remission after 4 weeks of induction treatment, you will have treatment with
      Consolidation 1, Consolidation 2, Consolidation 3 (Parts A and B), and then you will proceed
      to Maintenance therapy.

      If the level of blast cells in your blood is above a certain level at Day 15 of Induction but
      you achieved complete remission by Day 29, or if you achieved remission after 6 weeks of
      induction plus extended induction, then you will receive 1 course of Consolidation 1, 2
      courses of Consolidation 2, 2 courses of Consolidation 3 (Parts A and B), and then you will
      proceed to maintenance therapy.

      Consolidation 1 will last for 8 weeks (2 months). You will receive cyclophosphamide through a
      needle in your vein on Weeks 1 and 5. Cytarabine will be given as an injection just beneath
      the skin or by vein on or around Days 1-4 and Days 8-11 of each month. 6-Mercaptopurine will
      be taken by mouth on Days 1-14 of each month. Vincristine will be given by vein on Weeks 3-4
      of each month. PEG Asparaginase will be given by vein on Week 3 and 6 of each month. You will
      receive methotrexate through a needle through your spine weekly during Month 1 only. Blood
      (about 3 teaspoons) will be drawn for routine tests. You will have a spinal tap with spinal
      fluid tests during the intrathecal methotrexate dose. A spinal tap (also called a lumbar
      puncture) is when a special needle is inserted into the lower back through the space between
      the bones to draw a sample of the fluid that surrounds the spinal cord. You will have a bone
      marrow aspiration at the end of Month 2. To collect a bone marrow aspirate, an area of the
      hip or chest bone is numbed with anesthetic, and a small amount of bone marrow is withdrawn
      through a large needle.

      Consolidation 2 will last for 7 weeks. You will receive vincristine and methotrexate by vein
      every 10 plus or minus 2 days for 5 doses. You will receive PEG Asparaginase by vein in Weeks
      1 and 4. You will receive intrathecal methotrexate in Weeks 1 and 5. You will have a spinal
      tap with spinal fluid tests during the intrathecal methotrexate dose. Blood (about 3
      teaspoons) will be drawn every 2 weeks for routine tests.

      Consolidation 3 (Part A) will last for 4 weeks. You will receive vincristine and Doxorubicin
      by vein in Weeks 1, 2 and 3. Dexamethasone will be taken by mouth on Days 1-7 and Days 15-21.
      You will receive PEG Asparaginase by vein on Week 1. You will receive intrathecal
      methotrexate in Week 1.

      Consolidation 3 (Part B) will last for 4 weeks. You will receive cyclophosphamide by vein in
      Week 1. You will receive cytarabine by vein or as an injection for 4 days in a row in Weeks
      1-2. You will take 6-Thioguanine by mouth every day for the first 2 weeks. You will receive
      intrathecal methotrexate in Weeks 1 and 2. You will receive vincristine by vein on Weeks 3
      and 4. You will receive PEG Asparaginase by vein on Week 3.

      During Consolidation 3 (Part A and B), blood (about 3 teaspoons) will be drawn at least
      weekly for routine tests. Spinal fluid tests will be sent with each intrathecal methotrexate
      dose. Spinal taps will be done during each intrathecal chemotherapy dose

      Once you finish Consolidation, you will proceed to maintenance therapy.

      The Maintenance period for ALL patients will last for 24 months. If you have ALL, you will
      receive vincristine by vein every month. You will take dexamethasone by mouth for 5 days
      every month. You will take 6-Mercaptopurine by mouth once daily. You will take methotrexate
      by mouth every week. You will receive intrathecal methotrexate every 3 months for the first
      12 months of maintenance. You will have a spinal tap with spinal fluid tests during the
      intrathecal methotrexate dose.

      Maintenance for patients with LL will also last for 24 months. If you have LL, you will
      receive vincristine by vein every month. You will take dexamethasone by mouth for 5 days
      every month.

      You will take 6-Mercaptopurine by mouth once daily. You will take methotrexate by mouth every
      week.

      During the Maintenance period, all participants will have blood samples (about 1 to 3
      teaspoons each time) drawn every 3 months for routine tests.

      If you have LL, you will have an additional positron emission tomography (PET) scan and
      computed tomography (CT) scan at the end of the Maintenance period.

      Follow-Up Visits:

      Your study doctor will inform you of your follow-up visits in the clinic. At each follow-up
      visit there will be a physical exam and complete blood count. You will be followed-up for the
      next 3 years after your the last dose of your chemotherapy.

      Length of Study:

      You may remain on study for as long as you are benefiting. You may be taken off study if the
      disease gets worse or comes back during treatment, intolerable side effects occur, new
      information becomes available to your study doctor, if your doctor thinks it is in your best
      interest, or if you do not attend your appointments, which are scheduled at least once every
      3 months.

      This is an investigational study. The chemotherapy drugs used in this study are all FDA
      approved and commercially available. Up to 125 patients will take part in this study. All
      will be enrolled at MD Anderson.
    

Intervention name(s): Daunorubicin; Vincristine; PEG-asparaginase; Intrathecal Methotrexate; Cyclophosphamide; Cytarabine; Mercaptopurine; Methotrexate; Doxorubicin; Thioguanine
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Starting Dose 25 mg/m^2 by vein weekly; Starting Dose 2 mg by vein weekly; Starting Dose 2000 International units/m2 by vein in week 1; Starting Dose 12 mg on week 2 and week 5 injected into spinal fluid; Starting Dose 1g/m2 by vein in weeks 1 and 5; 75 mg/m2 subcutaneous or by vein for four consecutive days on days 1-4 and days 8-11 of both months; Starting Dose 60 mg/m2 by mouth on days 1-14 of each month; Starting Dose at 100 mg/m2 by vein and escalating by 50 mg/m2/dose every 10
+/- 2 days for 5 doses to toxicity (e.g myelosuppression or mucositis grade 3; 25 mg/m2 by vein in weeks 1, 2 and 3; 60 mg/m2 by mouth daily for two weeks
Other intervention name(s): Cerubidine®; Vincasar®; Oncaspar®; Rheumatrex®; Cytoxan®; Cytosar-U®; Purinethol®; Rheumatrex®; Adriamycin®; Thioguanine Tabloid®
Intervention MeSH terms: Cytarabine; Cyclophosphamide; Doxorubicin; Methotrexate; Vincristine; Daunorubicin; Asparaginase; Mercaptopurine; Thioguanine; Pegaspargase
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: acute lymphoblastic leukemia; acute lymphoblastic lymphoma; Leukemia; ALL; 6-Thioguanine; Cyclophosphamide; Cytarabine; Daunorubicin; Doxorubicin; Methotrexate; PEG-L-Asparaginase; Vincristine; Intrathecal Methotrexate; Mercaptopurine