R-MACLO-IVAM and Thalidomide in Untreated Mantle Cell Lymphoma

University of Miami

Status and phase

Completed

Phase 2

Conditions

Lymphoma

Treatments

Drug: Mesna

Drug: Leucovorin

Drug: Cyclophosphamide

Drug: Rituximab

Drug: Etoposide

Drug: Filgrastim (G-CSF)

Drug: Ifosfamide

Drug: Thalidomide

Drug: Vincristine

Drug: Granisetron

Drug: Methotrexate

Drug: Decadron

Drug: Cytarabine

Drug: Doxorubicin

Study type

Interventional

Funder types

Other

Identifiers

NCT00450801

SCCC-2003027 (Other Identifier)

WIRB-20051242 (Other Identifier)

20030165

Details and patient eligibility

About

RATIONALE: To evaluate the efficacy of a new high intensity chemotherapy regimen with thalidomide maintenance in patients with newly diagnosed mantle cell lymphoma

PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy followed by thalidomide works in treating patients with previously untreated mantle cell lymphoma.

Full description

OBJECTIVES:

Primary

Determine the progression-free survival of patients with previously untreated mantle cell lymphoma treated rituximab in combination with methotrexate, doxorubicin, cyclophosphamide, leucovorin, vincristine, ifosfamide, etoposide, cytarabine and mesna (MACLO/IVAM) followed by thalidomide.

Secondary

Determine the overall survival of patients treated with this regimen.
Determine the response rate in patients treated with this regimen.
Determine the toxicity of this regimen in these patients.

OUTLINE: During cycle 1, patients will receive rituximab intravenous (IV), granisetron IV, decadron IV, doxorubicin IV bolus, vincristine intravenous pyelogram (IVP) on day 1; cyclophosphamide IV on day 1-5; vincristine IVP on day 8; methotrexate IV, methotrexate by continuous infusion, then leucovorin IV until methotrexate level is below 0.01 nanomolar (nM) on day 10. Patients will receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 13 and continuing until blood counts recover.

When absolute neutrophil count (ANC) reaches1,500/mm^3, patients will start cycle 2. Patients will receive rituximab IV on day 1; cytarabine IV on day 1 and 2; ifosfamide IV, mesna IV, etoposide IV on day 1-5; and G-CSF SC daily beginning on day 7 and continuing until ANC is greater than 1,000 cells/mm^3.

Approximately 2-3 weeks later, patients receive another course of therapy as above.After cycle 4, patients in complete remission will take oral thalidomide until progression of disease. After completion of study treatment, patients are followed monthly for 3 months, every 3 months for 2 years, every 6 months for 3-5 years, and then annually thereafter or at study termination.

PROJECTED ACCRUAL: A total of 22 patients will be accrued for this study.

Enrollment

22 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Previously untreated, histologically confirmed mantle cell lymphoma.
Measurable or evaluable disease.
All stages are eligible.
Age > 18 years.
Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.
Adequate hepatic function:
- Bilirubin < 3 mg/dL.
- Transaminases (SGOT and/or SGPT) < than 2.5 times the upper limit of normal for the institution, unless due to lymphomatous involvement.
Serum creatinine < 1.5 mg/Dl.
Ability to give informed consent.
Women of childbearing potential must have a negative pregnancy test within 72 hours of entering into the study. Males and females must agree to use adequate birth control if conception is possible during the study. Women must avoid pregnancy and men avoid fathering children while in the study.
Life expectancy greater than 6 months.

Exclusion criteria

Previous chemotherapy, immunotherapy or radiotherapy for this lymphoma
Concurrent active malignancies, with the exception of in situ carcinoma of the cervix and basal cell carcinoma of the skin.
Grade 3 or 4 cardiac failure and/or ejection fraction < 50.
Psychological, familial, sociological or geographical conditions that do not permit treatment and/or medical follow-up required to comply with the study protocol.
Patients with a known history of HIV or AIDS
Presence of hepatitis or hepatitis B virus (HBV) infection
Pregnant or breast-feeding women.
Central nervous system (CNS) involvement

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

22 participants in 1 patient group

R-MACLO-IVAM-T

Experimental group

Description:

Rituximab, Methotrexate, Doxorubicin, Cyclophosphamide and Vincristine (cycle 1), followed by Rituximab, Ifosfamide (and Mesna), Etoposide and Cytarabine (cycle 2). These two cycles are repeated once, and patients achieving complete repose receive maintenance Thalidomide.

Treatment: