Treatment for Advanced B-Cell Lymphoma

NCT ID: NCT01859819

Last Updated: 2022-10-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-01-31
• Study Completion Date: 2021-06-30

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).

Conditions

Diffuse Large Cell Lymphoma; Burkitt's Lymphoma; High Grade B-cell Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group B

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 Type: EXPERIMENTAL

Rituximab

Intervention Type: DRUG

IT Cytarabine

Intervention Type: DRUG

Group C, CNS negative

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 Type: EXPERIMENTAL

Rituximab

Intervention Type: DRUG

IT Cytarabine

Intervention Type: DRUG

Group C, CNS Positive

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 Type: EXPERIMENTAL

Rituximab

Intervention Type: DRUG

IT Cytarabine

Intervention Type: DRUG

Interventions

Rituximab

Intervention Type: DRUG

IT Cytarabine

Intervention Type: DRUG

Other Intervention Names

RITUXAN®, IDEC-C2B8) NSC #687451, IND #10385; DEPOCYT® (Cytarabine Liposome Injection)

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 31 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

New York Medical College

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mitchell S Cairo, MD

Role: PRINCIPAL_INVESTIGATOR

New York Medical College

Stanton Goldman, MD

Role: STUDY_DIRECTOR

Medical City Children's Hospital, Dallas

Locations

Roswell Park Cancer Institute

Buffalo, New York, United States

New York Medical College

Valhalla, New York, United States

Levine Children's Hospital

Charlotte, North Carolina, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

University of Utah

Salt Lake City, Utah, United States

Countries

United States

References

Goldman S, Barth M, Shiramizu B, Shi Q, Hochberg J, Klejmont L, Harrison L, Basso J, Chu Y, Islam H, Gerard P, Agsalda-Garcia M, Shieh T, Oesterheld J, Heym K, Kirov I, Drachtman R, Harker-Murray P, Perkins S, Miles RR, Cairo M. A dose substitution of anthracycline intensity with dose-dense rituximab in children and adolescents with good-risk mature B-cell lymphoma. Leukemia. 2021 Oct;35(10):2994-2997. doi: 10.1038/s41375-021-01256-8. Epub 2021 May 3. No abstract available.

Reference Type: BACKGROUND

PMID: 33941850 (View on PubMed)

Other Identifiers

L 10,753

Identifier Type: OTHER

Identifier Source: secondary_id

NYMC-157

Identifier Type: -

Identifier Source: org_study_id