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
Intervention: Daunorubicin; Vincristine; PEG-asparaginase; Intrathecal Methotrexate; Cyclophosphamide; Cytarabine; Mercaptopurine; Methotrexate; Doxorubicin; Thioguanine
Intervention description: 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
Intervention MeSH terms: Cytarabine; Cyclophosphamide; Doxorubicin; Methotrexate; Vincristine; Daunorubicin; Asparaginase; Mercaptopurine; Thioguanine; Pegaspargase
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 120.0
Sex: All
Minimum age: 12 Years
Maximum age: 40 Years
Healthy volunteers: No
Keywords: acute lymphoblastic leukemia; acute lymphoblastic lymphoma; Leukemia; ALL; 6-Thioguanine; Cyclophosphamide; Cytarabine; Daunorubicin; Doxorubicin; Methotrexate; PEG-L-Asparaginase; Vincristine; Intrathecal Methotrexate; Mercaptopurine

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients must have precursor-B or T-lymphoblastic leukemia or lymphoblastic lymphoma.

          2. Patients must be untreated or have had only one prior chemotherapy regimen for ALL or
             LL . Previously treated patients will be analyzed separately.

          3. Age between 12 to 40 years old

          4. Patients with Central Nervous System (CNS) disease or testicular disease are eligible.

          5. Intrathecal therapy with cytarabine is allowed prior to registration for patient
             convenience. This is usually done at the time of the diagnostic bone marrow or venous
             line placement to avoid a second lumbar puncture. Systemic chemotherapy must begin
             within 72 hours of the first intrathecal treatment.

          6. Signed informed consent prior to the start of systemic therapy. In the event of
             enrollment of a minor patient, an attempt to obtain assent from the patient must be
             documented, and parental consent must be signed.

          7. Echocardiogram should be done within 72 hours of starting therapy if there are cardiac
             risk factors (e.g., history of hypertension or of myocardial infarction)

          8. Creatinine should be < 3 mg/dL bilirubin < 3 mg/dl unless felt to be due to disease

          9. Zubrod Performance status of <3

         10. Patients who received steroids more than 72 hours prior to study enrollment are
             eligible but will be analyzed separately

        Exclusion Criteria:

          1. Age less than twelve years of age or greater than 40 years.

          2. More than one prior treatment regimen for ALL or LL.

          3. The patient is pregnant or unwilling to practice appropriate birth control.

          4. Presence of the Philadelphia chromosome t(9;22)