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

October 12, 2015 updated by: Izidore Lossos, University of Miami

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

22

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Miami, Florida, United States, 33136
        • University of Miami Sylvester Comprehensive Cancer Center - Miami

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: R-MACLO-IVAM-T
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.
Drug: Rituximab
Rituximab 375 mg/m2 IV, Days 1 of all cycles
Other Names:
  • Rituxan
Drug: Cyclophosphamide
Cyclophosphamide 800 mg/m2 IV, Day 1, Cyclophosphamide 200 mg/m2 IV Days 2 - 5, Cycles 1 and 3. Cyclophosphamide will be given in 100 cc NS IV over 30 minutes.
Other Names:
  • Cytoxan
Drug: Cytarabine
Cytarabine 2 grams/m2 IV every 12 hours x 4 doses, Days 1 and 2, Cycles 2 and 4.
Other Names:
  • AraC
Drug: Doxorubicin
Doxorubicin 45 mg/m2 IV bolus, Day 1, Cycles 1 and 3
Other Names:
  • Adriamycin
Drug: Etoposide
Etoposide 60 mg/m2 IV daily x 5 days, Cycles 2 and 4
Other Names:
  • VP16
Drug: Ifosfamide
Ifosfamide 1.5 grams/m2 IV once a day (QD) x 5 days, Cycles 2 and 4
Other Names:
  • Ifex
Drug: Leucovorin
Leucovorin 180 mg/m2 IV beginning 36 hours after start of methotrexate infusion and then 12 mg/m2 IV every 6 hours until methotrexate level is below 0.01 nM. Day 10, Cycles 1 and 3.
Other Names:
  • Folinic Acid
Drug: Methotrexate
Methotrexate 1,200 mg/m2 in 250 cc 5 percent dextrose in water (D5W) IV over 1 hour followed by Methotrexate 5,520 mg/m2 in 1,000 cc D5W by continuous infusion over 23 hours (240 mg/m2 every hour for 23 hours). Day 10, Cycles 1 and 3.
Other Names:
  • amethopterin
Drug: Thalidomide
Maintenance therapy.
Other Names:
  • Thalomid
Drug: Vincristine
Vincristine 1.5 mg/m2 IVP (maximum of 2 mg), Day 1 and 8 , Cycles 1 and 3.
Other Names:
  • Oncovin
Drug: Mesna
Mesna 360 mg/m2 IV every 3 hours x 5 days, Cycles 2 and 4
Other Names:
  • Mesnex
Drug: Filgrastim (G-CSF)
G-CSF 480 mcg subcutaneous (SQ) starting Day 13 (Cycles 1 and 3), Day 7 (Cycles 2 and 4)
Other Names:
  • Neupogen
Drug: Granisetron
Granisetron 1 mg IV on Day 1, Cycle 1 and 3
Other Names:
  • Sancuso
  • Granisol
Drug: Decadron
Decadron 10 mg IV on Day 1, Cycles 1 and 3
Other Names:
  • Baycadron
  • Ozurdex
  • Maxidex

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival Rate
Time Frame: Up to 5 years
Percentage of participants achieving progression-free survival at 1, 3 and 5 years after the start of protocol therapy, based upon the International Working Group Response Criteria for Non-Hodgkin's Lymphoma (NHL). Progression is defined as a ≥ 50% increase from nadir in the product of the two largest perpendicular diameters (PPD-size) of any previously identified abnormal node, or appearance of any new lesion.
Up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival Rate
Time Frame: Up to 5 years
Percentage of participants who are alive up to five years after receipt of protocol therapy.
Up to 5 years
Response Rate
Time Frame: Up to 5 years
Percentage of participants achieving complete response (CR) to protocol therapy according to International Working Group Response Criteria for Non-Hodgkin's Lymphoma (NHL) using the CT imaging method. Patients were classified by best tumor response; CR was defined as normalization of the lactate dehydrogenase (LDH), complete disappearance of disease-related symptoms and lymph nodes, and clearance of lymphoma from involved organs; complete response unconfirmed (CRu) as a residual lymph node greater than 1.5 cm in greatest transverse diameter that had regressed by more than 75% or an indeterminate bone marrow examination; partial response (PR) as greater than 50% reduction in the involved lymph nodes, or disappearance of the involved lymph nodes but persistent bone marrow involvement; relapse/progression as new or increased lymph nodes, organomegaly, or reappearance of bone marrow involvement.
Up to 5 years
Number of Patients Experiencing Adverse Events.
Time Frame: Up to 5 years
Number of patients experiencing adverse events during the course of protocol therapy.
Up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Miami

Investigators

  • Study Chair: Izidore S. Lossos, MD, University of Miami Sylvester Comprehensive Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2004

Primary Completion (Actual)

July 1, 2015

Study Completion (Actual)

July 1, 2015

Study Registration Dates

First Submitted

March 20, 2007

First Submitted That Met QC Criteria

March 20, 2007

First Posted (Estimate)

March 22, 2007

Study Record Updates

Last Update Posted (Estimate)

November 10, 2015

Last Update Submitted That Met QC Criteria

October 12, 2015

Last Verified

October 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20030165
  • SCCC-2003027 (Other Identifier: University of Miami Sylvester Comprehensive Cancer Center)
  • WIRB-20051242 (Other Identifier: Western Institutional Review Board)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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