Augmented Berlin-Frankfurt-Munster Therapy Plus Ofatumumab for Young Adults With Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma
Condition: Leukemia; Precursor-B Acute Lymphoblastic Leukemia; Lymphoblastic Lymphoma; Lymphoma
MeSH terms: Lymphoma; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Lymphoma, Non-Hodgkin
Intervention: Cytarabine; Daunorubicin; Vincristine; Prednisone; PEG asparaginase; Ofatumumab; Rituximab; Methotrexate; Cyclophosphamide; Mercaptopurine; Doxorubicin; Dexamethasone acetate; Thioguanine
Intervention description: Participants initially receive intrathecal treatment using Cytarabine 100 mg on Day 1. Induction chemotherapy must begin within 3 days of the intrathecal Cytarabine dose.
Consolidation Therapy 1: Cytarabine 75 mg/m2 subcutaneously Days 1 - 4 and 8 - 11.
Consolidation Therapy 3B: Cytarabine 75 mg/m2 subcutaneously Days 1 - 4 and Days 8 - 11.; Induction Therapy: Daunorubicin 25 mg/m2 by vein weekly for 4 doses.; Induction Therapy: Vincristine 1.5 mg/m2 by vein weekly for 4 doses.
Consolidation Therapy 1: Vincristine 1.5 mg/m2 by vein Week 3 and Week 4.
Consolidation Therapy 2: Vincristine 1.5 mg/m2 by vein every 10 days for 5 doses.
Consolidation Therapy 3A: Vincristine 1.5 mg/m2 by vein weekly for 3 doses.
Consolidation Therapy 3B: Vincristine 1.5 mg/m2 by vein Weeks 3 and 4.
Maintenance Therapy (24 months): Vincristine 1.5 mg/m2 by vein every 28 days.; Induction Therapy: Prednisone 60 mg/m2/day by mouth for 28 days.; Induction Therapy: PEG asparaginase 2000 IU/m2 by vein on Day 4 of induction.
Consolidation Therapy 1: PEG-asparaginase 2000 IU/m2 by vein Week 3 and Week 7.
Consolidation Therapy 2: PEG-asparaginase 2000 IU/m2 by vein Weeks 1 and 4.
Consolidation Therapy 3A: PEG-asparaginase 2000 IU/m2 by vein in Week 1.
Consolidation Therapy 3B: PEG-asparaginase 2000 IU/m2 by vein Week 3.; Induction Therapy: Ofatumumab 300 mg by injection or vein on Day 2 and Ofatumumab 2000 mg by injection or vein on Day 15.
Consolidation Therapy 1: Ofatumumab 2000 mg by injection or vein Week 1 and Week 5.
Consolidation Therapy 2: Ofatumumab 2000 mg by injection or vein Week 1 and Week 5.
Consolidation Therapy 3A: Ofatumumab 2000 mg by injection or vein Week 1 and Week 3.; Induction Therapy: If Ofatumumab not available, Rituximab 375 mg/m2 by vein on Day 1 and on Day 15.
Consolidation Therapy 1: If Ofatumumab not available, Rituximab 375 mg/m2 by vein Week 1 and Week 5.
Consolidation Therapy 2: If Ofatumumab not available, Rituximab 375 mg/m2 by vein Week 1 and Week 5.
Consolidation Therapy 3A: If Ofatumumab not available, Rituximab 375 mg/m2 by vein Week 1 and Week 3.; Induction Therapy: Intrathecal methotrexate 12 mg on Day 8 and Day 29.
Consolidation Therapy 1: Intrathecal methotrexate 12 mg Weekly, Weeks 1 - 4.
Consolidation Therapy 2: Methotrexate by vein every 10 days starting at 100 mg/m2 and increasing by 50 mg/m2 as tolerated. and Intrathecal methotrexate 12 mg Week 1.
Consolidation Therapy 3A: Intrathecal methotrexate 12 mg in Week 1.
Consolidation Therapy 3B: Intrathecal methotrexate 12 mg Week 1 and 2.
Maintenance Therapy (24 months): Methotrexate 20 mg/m2 by mouth weekly, hold on days of intrathecal methotrexate.
Maintenance Therapy (24 months): Intrathecal methotrexate 12 mg every 3 months for 4 doses.; Consolidation Therapy 1: Cyclophosphamide 1 gram/m2 by vein Week 1 and Week 5.
Consolidation Therapy 3B: Cyclophosphamide 1 gram/m2 by vein Week 1.; Consolidation Therapy 1: Mercaptopurine 60 mg/m2/day by mouth Days 1 - 14.
Maintenance Therapy (24 months): Mercaptopurine 75 mg/m2 by mouth nightly.; Consolidation Therapy 3A: Doxorubicin 25 mg/m2 by vein weekly for 3 doses.; Consolidation Therapy 3A: Dexamethasone 10 mg/m2 by mouth on Days 1 - 7 and Days 15 - 21.
Maintenance Therapy (24 months): Dexamethasone 6 mg/m2/day by mouth Days 1 - 5 every 28 days.; Consolidation Therapy 3B: Thioguanine 60 mg/m2/day by mouth for 14 days.
Intervention MeSH terms: Cytarabine; Dexamethasone; Prednisone; Dexamethasone acetate; Cyclophosphamide; Rituximab; Doxorubicin; Liposomal doxorubicin; Methotrexate; Vincristine; Daunorubicin; Asparaginase; Mercaptopurine; Ofatumumab; Pegaspargase; Thioguanine; BB 1101
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 12 Years
Maximum age: 30 Years
Healthy volunteers: No
Keywords: Leukemia; Precursor-B acute lymphoblastic leukemia; ALL; Lymphoblastic lymphoma; LL; Lymphoma; Cytarabine; Ara-C; Cytosar; DepoCyt; Cytosine Arabinosine Hydrochloride; Daunorubicin; Daunorubicin Hydrochloride; Cerubidine; Daunomycin; DNR; Vincristine; Prednisone; PEG asparaginase; Pegaspargase; Oncaspar; Polyethylene glycol conjugated lasparaginase-H; Ofatumumab; Arzerra; Rituximab; Rituxan; Methotrexate; Cyclophosphamide; Cytoxan; Neosar; Mercaptopurine; 6-mercaptopurine; Purinethol; 6-MP; Doxorubicin; Doxorubicin hydrochloride; Adriamycin PFS; Adriamycin RDF; Adriamycin; Rubex; Dexamethasone; Decadron; Thioguanine; 6-thioguanine

Summary:

      The goal of this clinical research study is to learn if a chemotherapy combination called
      augmented Berlin-Frankfurt-Munster (BFM), when also combined with ofatumumab or rituximab,
      can help to control precursor-B ALL or LL in patients who are 12-30 years of age. The safety
      of these drug combinations will also be studied.

      Augmented BFM is made up of daunorubicin, vincristine, prednisone, dexamethasone, PEG
      asparaginase, and methotrexate.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients must have precursor-B lymphoblastic leukemia or 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 30 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 7 days 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 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.

         11. Lymphoblasts may have any positive expression of cluster of differentiation antigen 20
             (CD20) for ofatumumab administration.

        Exclusion Criteria:

          1. Age less than twelve years of age or greater than 30 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)

          5. Laboratory or clinical evidence of active infectious hepatitis.