Clinical trial NCT00450801: R-MACLO-IVAM and Thalidomide in Untreated Mantle Cell Lymphoma
Official title: Phase II Study of Rituximab in Combination With Methotrexate, Doxorubicin, Cyclophosphamide, Leucovorin, Vincristine, Ifosfamide, Etoposide, Cytarabine and Mesna (MACLO/IVAM) in Patients With Previously Untreated Mantle Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma
Keywords: contiguous stage II mantle cell lymphoma
noncontiguous stage II mantle cell lymphoma
stage I mantle cell lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma
Lead sponsor: University of Miami
Sponsor class: OTHER
First posted: 2007-03-22
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression-free Survival Rate
timeFrame: Up to 5 years
Secondary outcomes:
measure: Overall Survival Rate
timeFrame: Up to 5 years
measure: Response Rate
timeFrame: Up to 5 years
measure: Number of Patients Experiencing Adverse Events.
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami Sylvester Comprehensive Cancer Center - Miami
state: Florida
Study officials:
affiliation: University of Miami Sylvester Comprehensive Cancer Center
name: Izidore S. Lossos, MD
role: STUDY_CHAIR
References:
citation: Lossos IS, Hosein PJ, Morgensztern D, Coleman F, Escalon MP, Byrne GE Jr, Rosenblatt JD, Walker GR. High rate and prolonged duration of complete remissions induced by rituximab, methotrexate, doxorubicin, cyclophosphamide, vincristine, ifosfamide, etoposide, cytarabine, and thalidomide (R-MACLO-IVAM-T), a modification of the National Cancer Institute 89-C-41 regimen, in patients with newly diagnosed mantle cell lymphoma. Leuk Lymphoma. 2010 Mar;51(3):406-14. doi: 10.3109/10428190903518345.
citation: Alderuccio JP, Saul EE, Iyer SG, Reis IM, Alencar AJ, Rosenblatt JD, Lossos IS. R-MACLO-IVAM regimen followed by maintenance therapy induces durable remissions in untreated mantle cell lymphoma - Long term follow up results. Am J Hematol. 2021 Jun 1;96(6):680-689. doi: 10.1002/ajh.26163. Epub 2021 Apr 7.