Treatment for Advanced B-Cell Lymphoma

Phase 2

Completed

• Conditions: Diffuse Large Cell Lymphoma; High Grade B-cell Lymphoma; Burkitt's Lymphoma
• Interventions: Drug: Rituximab; Drug: IT Cytarabine

• Registration Number: NCT01859819
• Lead Sponsor: New York Medical College

Brief Summary

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 anthracycline (doxorubicin) in good risk patients with the addition of rituximab to the FAB chemotherapy backbone (Immunochemotherapy).

Detailed Description

Not available

Study Timeline

• Study Start: 2013-01
• Study First Submitted: 2013-04-16
• Study First Submitted QC: 2013-05-20
• Study First Posted: 2013-05-22
• Primary Completion: 2020-06
• Study Completion: 2021-06
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-24
• Last Update Posted: 2022-10-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

• 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.

No previous chemotherapy. Patients who have received emergency irradiation and/or steroid therapy will be eligible ONLY if started on protocol therapy not more than 72 hours from the start of radiotherapy or steroids. Bone marrow and cerebrospinal fluid MUST be obtained before steroids are given for patient to be eligible for the study.

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Exclusion Criteria

• Patients with newly diagnosed Group A (low risk) lymphoma. Patients with Group B (intermediate risk) if classified as Murphy Stage III/IV and diagnostic LDH > 2 XULN and patients with primary mediastinal B-cell lymphoma (PMBL).
• Patients who have received any steroids in the week prior to diagnosis except as stated in Section 4.1.4 of the protocol.
• 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.
• No prior solid organ transplantation.
• 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).

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

4.2.7 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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Group B	Rituximab	De-novo Mature CD 20 + B-NHL excluding PMBL histology. Good Risk FAB Group B includes patients with St. Jude Stages I /II (unresected) and stage III/IV with diagnostic LDH \<2 X ULN. REDUCTION: Cyclophosphamide, Vincristine, Prednisone, IT Methotrexate INDUCTION:Rituximab, Vincristine, Methotrexate, Leukovorin, Cyclophosphamide, Doxorubicin CONSOLIDATION: Rituximab, Methotrexate, Leukovorin, Cytarabine
Group B	IT Cytarabine	De-novo Mature CD 20 + B-NHL excluding PMBL histology. Good Risk FAB Group B includes patients with St. Jude Stages I /II (unresected) and stage III/IV with diagnostic LDH \<2 X ULN. REDUCTION: Cyclophosphamide, Vincristine, Prednisone, IT Methotrexate INDUCTION:Rituximab, Vincristine, Methotrexate, Leukovorin, Cyclophosphamide, Doxorubicin CONSOLIDATION: Rituximab, Methotrexate, Leukovorin, Cytarabine
Group C, CNS Positive	Rituximab	De-novo Mature CD 20 + B-NHL with CNS involvement: 1. Any L3 blasts in CSF 2. Cranial nerve palsy (if not explained by extracranial tumor) 3. Clinical spinal cord compression 4. Isolated intracerebral mass 5. Parameningeal extension: cranial and/or spinal REDUCTION: Cyclophosphamide, Vincristine, Prednisone, IT Methotrexate, IT Cytarabine INDUCTION: Rituximab, Methotrexate, Leukovorin, Cyclophosphamide, Doxorubicin, IT Methotrexate, IT Cytarabine, IT Liposomal ARA-C, Vincristine CONSOLIDATION: Rituximab, Cytarabine, Etoposide MAINTENANCE: Vincristine, Cyclophosphamide, Methotrexate, Leukovorin, Doxorubicin, IT Liposomal ARA-C,
Group C, CNS negative	IT Cytarabine	De-novo Mature CD 20 + B-ALL (\> 25% Bone marrow blasts) without CNS involvement. REDUCTION: Cyclophosphamide, Vincristine, Prednisone, IT Methotrexate, IT Cytarabine INDUCTION: Rituximab, Vincristine, Methotrexate, Leukovorin, Cyclophosphamide, Doxorubicin, IT Methotrexate, IT Cytarabine CONSOLIDATION: Rituximab, Cytarabine, Etoposide MAINTENANCE: Vincristine, Prednisone, Methotrexate, Leukovorin, Cyclophosphamide, Doxorubicin, Etoposide, Cytarabine
Group C, CNS Positive	IT Cytarabine	De-novo Mature CD 20 + B-NHL with CNS involvement: 1. Any L3 blasts in CSF 2. Cranial nerve palsy (if not explained by extracranial tumor) 3. Clinical spinal cord compression 4. Isolated intracerebral mass 5. Parameningeal extension: cranial and/or spinal REDUCTION: Cyclophosphamide, Vincristine, Prednisone, IT Methotrexate, IT Cytarabine INDUCTION: Rituximab, Methotrexate, Leukovorin, Cyclophosphamide, Doxorubicin, IT Methotrexate, IT Cytarabine, IT Liposomal ARA-C, Vincristine CONSOLIDATION: Rituximab, Cytarabine, Etoposide MAINTENANCE: Vincristine, Cyclophosphamide, Methotrexate, Leukovorin, Doxorubicin, IT Liposomal ARA-C,
Group C, CNS negative	Rituximab	De-novo Mature CD 20 + B-ALL (\> 25% Bone marrow blasts) without CNS involvement. REDUCTION: Cyclophosphamide, Vincristine, Prednisone, IT Methotrexate, IT Cytarabine INDUCTION: Rituximab, Vincristine, Methotrexate, Leukovorin, Cyclophosphamide, Doxorubicin, IT Methotrexate, IT Cytarabine CONSOLIDATION: Rituximab, Cytarabine, Etoposide MAINTENANCE: Vincristine, Prednisone, Methotrexate, Leukovorin, Cyclophosphamide, Doxorubicin, Etoposide, Cytarabine

Primary Outcome Measures

Name	Time	Method
To determine if disease response rate will improve with this combination of therapy.	1 year	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 response rates compared to historical controls (Subgroup I).

Secondary Outcome Measures

Name	Time	Method
To determine if the combination of IT Depocyte®, Rituximab and FAB Chemotherapy is safe.	1 year	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) as measured by reported serious adverse events.

Trial Locations

Locations (5)

Levine Children's Hospital; 🇺🇸 Charlotte, North Carolina, United States

University of Oklahoma Health Sciences Center; 🇺🇸 Oklahoma City, Oklahoma, United States

Roswell Park Cancer Institute; 🇺🇸 Buffalo, New York, United States

New York Medical College; 🇺🇸 Valhalla, New York, United States

University of Utah; 🇺🇸 Salt Lake City, Utah, United States