REBOOT

Principal Investigator: Phillip Barnette
Keywords: Pediatrics , Oncology , Non-Hodgkin Lymphoma , Burkitt's Lymphoma , Burkitt's Leukemia Department: Pediatric Administration
IRB Number: 00063155 Co Investigator:  
Specialty: Oncology
Sub Specialties:
Recruitment Status: Recruiting

Contact Information

Jennifer Craig
jennifer.craig@imail.org
8016624715

Brief Summary

Hypothesis and Objectives

To safely reduce the burden of therapy in children, adolescents and young adults with mature B-NHL by reducing the number of intrathecal (IT) injections by the introduction of IT Liposomal Cytarabine (L-ARA-C, [Depocyt®]) and reducing the dose of anthracyline (doxorubicin) in good risk patients with the addition of rituximab to the FAB chemotherapy backbone (Immunochemotherapy).

Primary Objective

1.To determine if the addition of intrathecal ([IT] [Depocyt®]) and reduction of standard IT dosing and the reduction of anthracycline exposure (doxorubicin) (60%) within the ANHL01P1 FAB/LMB B4 + Rituximab chemoimmunotherapy backbone in children, adolescents and young adults with good risk CD20+ mature B-NHL (Stage I and II unresected and Stage III/IV with LDH < 2 UNL) will result in similar outcomes compared to historical controls (Subgroup I).

Secondary Objectives

1.  To determine the safety and efficacy of reduction of IT therapy and substitution with L-ARA-C (Depocyte®) within ANHL01P1 FAB/LMB Group B4 (reduced anthracycline) plus rituximab chemotherapy backbone in children, adolescents and young adults with intermediate risk de-novo mature B-NHL (Group B Stage III with LDH > 2X UNL and stage IV) (Subgroup IB).

 

2.  To determine the safety and efficacy of reduction of IT therapy and substitution with L-ARA-C (Depocyte®) within ANHL01P1 FAB/LMB Group C1 plus rituximab chemotherapy backbone in children, adolescents and young adults with advanced risk de-novo mature B-NHL (Group C BM±CNS) (Subgroup II).

Tertiary Objectives

1.  To measure the change in cardiac biomarkers, cardiac troponin T (cTnT) and N-terminial pro-brain       natriuretic peptide (NT-proBNP) and echocardiograms after doxorubicin treatment in children,  adolescents and young adults with CD20+ mature B-NHL.

2.  To measure the change in CSF minimal residual disease (MRD) pre and post administration of L-ARA-   C in children, adolescents and young adults with CD20+ CNS mature B-NHL.

3.  To measure CSF rituximab levels after systemic rituximab administration in children, adolescents and young adults with CD20+ mature B-NHL.

4.  To further define the molecular, genetic, cytogenetics and proteomic characteristics of children, adolescent and young adults with CD20+ mature B-NHL.

 

Detailed Description

Many children with advanced B-cell leukemia/lymphoma can be cured with current treatments, but these standard treatments do not stop every child’s cancer from coming back. In addition, because B-cell leukemia and lymphoma can go to the central nervous system (brain and spine), children require frequent injections of chemotherapy directly into the spinal fluid (intrathecal) to prevent and/or treat involvement of the brain and spine. These injections, while usually well tolerated, generally require sedation and/or anesthesia. Researchers would like to find out the effects, good and bad, of adding two new drugs (intrathecal liposomal ara-c and rituximab) to the standard drugs. Some previous research has shown that these drugs may be of benefit.

Inclusion Criteria

Diagnosis: Newly diagnosed mature B-lineage (CD20 positive) Leukemia/Lymphoma

  1. Diffuse Large Cell Lymphoma  (NOT primary mediastinal B-cell lymphoma)
  2. Burkitt’s Lymphoma
  3. High Grade B-cell Lymphoma---Burkitt’s like

B-Cell Anaplastic Large cell Ki 1 positive lymphomas, Primary Mediastinal B-Cell Lymphoma (PMBL), and B-Lymphoblastic lymphomas are ineligible.

Stage of Disease: Revised with Amendment 11: Pretreatment imaging, pathology and bone marrow studies need to be done to document International Pediatric NHL Staging System (IPSN) [Rosolen, 2015 #6] and FAB Groyp Classification (APPENDIX III) and determine Group B (good and intermediate risk) and Group C Therapy Stratification.

 

Pretreatment imaging, pathology and bone marrow studies need to be done to document Murphy and FAB Staging Classification (APPENDIX III) and determine Group B (ONLY GOOD RISK) and Group C Therapy Stratification.

Hepatitis B Screening  (This screening must be done for eligibility BUT the results are not needed for enrollment) 

  • Patient’s Hepatitis B immunization status (Vaccination Yes or No)
  • HBsAg
  • Anti-HBs antibody
  • Anti-HBc antibody

3.    Age: Age >= 3 year and < 31 years at study enrollment.

4.  Prior Therapy: Revised with Amendment 11: No previous chemotherapy with the exception of intrathecal chemotherapy administered with the diagnostic lumbar puncture, or emergency steroids. Patients who have received emergency irradiation and/or steroid therapy will be eligible ONLY if started on protocol therapy not more than 1 week 72 hours from the start of radiotherapy or steroids.  Bone marrow and cerebrospinal fluid MUST should be obtained before steroids are given for patient to be eligible for the study. Patients with clinical and/or radiographic CNS disease (FAB Group C: CNS+) may start therapy without diagnostic lumbar puncture if clinically contraindicated.

A short course of corticosteroids (<10 days) given and stopped more than 8 days before diagnosis and initial work up does not exclude a patient from being entered onto the study. Patients who have received any steroids in the week prior to diagnosis are not eligible for the study.

5.    Informed Consent: The patient and/or the patient’s legally authorized guardian must acknowledge in writing that consent to become a study subject has been obtained, in accordance with institutional policies approved by the U.S. Department of Health and Human Services.

6.    Protocol Approval: Approval for the use of this treatment protocol by the individual institution's Human Rights Committee must be obtained, in accordance with the institutional assurance policies of the U.S. Department of Health and Human Services.

 

Exclusion Criteria

1. Patients with newly diagnosed Group A (low risk) lymphoma and patients with primary mediastinal B-cell lymphoma (PMLBL).

2. Patients who have received any steroids in the week prior to diagnosis except as stated in Section 4.1.4.

3.  No congenital or acquired immune deficiency.  These patients are excluded due to the expected intense immunosuppression, increased risk of opportunistic infections, and higher expected septic death rate in this subgroup of patients with this proposed therapy.

4. No prior solid organ transplantation.

5. Patients with previous malignancies that have been treated with systemic chemotherapy with alkylator or anthracycline therapy.  The latter group of patients are excluded due to an expected increase in late effects (eg. late cardiac toxicity, secondary malignancies, sterility, etc.).

Patients with known G6PD deficiency are NOT ELIGIBLE for Rasburicase therapy. Patients with G6PD deficiency should be treated with alkalinization, IV hydration and po and/or IV allopurinol during the reduction phase (COP).

6. Patients with serious (sepsis, pneumonia, etc.) proven or suspected infections at diagnosis will be excluded.

7. Pregnancy or Breast-Feeding: No information is available regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal.  Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.