Rituximab and Combination Chemotherapy in Treating Patients With Previously Untreated Mantle Cell Lymphoma

July 31, 2023 updated by: Izidore Lossos, MD, University of Miami

Phase II Study of Rituximab in Combination With Methotrexate, Doxorubicin, Cyclophosphamide, Leucovorin, Vincristine, Ifosfamide, Etoposide, Cytarabine and Mesna (R-MACLO/VAM) in Patients With Previously Untreated Mantle Cell Lymphoma

The investigator(s) hypothesize that Rituximab together with combination chemotherapy, followed by Rituximab maintenance therapy, will provide better disease control with improved response rates and overall survival in patients with previously untreated Mantle Cell Lymphoma (MCL).

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

25

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, 33186
        • University of 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

Description

Inclusion Criteria:

  1. Previously untreated, histologically confirmed mantle cell lymphoma,
  2. Measurable or evaluable disease (at least one site with >1.5 cm in diameter
  3. All stages are eligible
  4. Age > 18 years
  5. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2

  6. Adequate hepatic function:

    • Bilirubin < 3 mg/dL
    • Transaminases (serum glutamic oxaloacetic transaminase (SGOT) and/or serum glutamate-pyruvate transaminase (SGPT)) < than 2.5 times the upper limit of normal for the institution, unless due to lymphomatous involvement
  7. Serum creatinine< 1.5 mg/dl
  8. Ability to give informed consent
  9. 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.
  10. Life expectancy greater than 6 months.

Exclusion Criteria:

  1. Previous chemotherapy, immunotherapy or radiotherapy for this mantle cell lymphoma
  2. Concurrent active malignancies, with the exception of in situ carcinoma of the cervix and basal cell carcinoma of the skin.
  3. Grade 3 or 4 cardiac failure and/or ejection fraction < 50.
  4. Psychological, familial, sociological or geographical conditions that do not permit treatment and/or medical follow-up required to comply with the study protocol.
  5. Patients with a known history of human immunodeficiency virus (HIV) or Acquired Immunodeficiency Syndrome (AIDS).
  6. Presence of hepatitis or hepatitis B virus (HBV) infection.
  7. Pregnant or breast-feeding women.
  8. 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

Four 21-day cycles, followed by Maintenance Therapy as follows:

  • Cycles 1 and 3: Rituximab, Doxorubicin, Vincristine, Cyclophosphamide, Methotrexate, Leucovorin, and G-CSF per study protocol.
  • Cycles 2 and 4: Rituximab, Cytarabine, Ifosfamide, Mesna, Etoposide, and G-CSF per study protocol.
  • Maintenance Therapy: Rituximab: For study participants in complete remission. Every 6 months for up to 3 years, per study protocol.
Biological: G-CSF
Granulocyte-colony stimulating factor (G-CSF) 480 mcg subcutaneously (SQ) starting on Day 13 of Cycles 1 and 3; and Day 7 of Cycles 2 and 4, per study protocol.
Other Names:
  • Filgrastim
  • Neupogen
Drug: Rituximab
Rituximab 375 mg/m^2 intravenously (IV) on Day 1 for 4 Cycles, per study protocol. For study participants achieving complete remission, during maintenance therapy every 6 months for up to three years, per study protocol.
Other Names:
  • Rituxan
Drug: Cyclophosphamide
Cyclophosphamide 800 mg/m^2 IV on Day 1 and 200 mg/m^2 IV on Days 2 through 5 of Cycles 1 and 3, per study protocol.
Other Names:
  • Cytoxan
Drug: Cytarabine
Cytarabine 2 grams/m^2 IV on Days 1 and 2 of Cycles 2 and 4, per study protocol.
Other Names:
  • AraC
Drug: Doxorubicin
Doxorubicin 45 mg/m^2 IV bolus Day 1 of Cycles 1 and 3, per study protocol.
Other Names:
  • Adriamycin
Drug: Etoposide
Etoposide 60 mg/m^2 IV on Days 1 through 5 of Cycles 2 and 4, per study protocol.
Other Names:
  • VP16
Drug: Ifosfamide
Ifosfamide 1.5 grams/m^2 IV on Days 1 through 5 of Cycles 2 and 4, per study protocol.
Other Names:
  • Ifex
Drug: Leucovorin
Leucovorin: 100 mg/m^2 IV beginning 36 (+/-4) hours after start of Methotrexate infusion, and then 10 mg/m^2 at 6 hour (+/- 30 min) intervals until Methotrexate level is < 0.1 µmol/L during Cycles 1 and 3 per study protocol.
Other Names:
  • Folinic acid
Drug: Mesna
Mesna 360 mg/m^2 IV on Days 1 through 5 of Cycles 2 and 4, per study protocol.
Other Names:
  • Mesnex
Drug: Methotrexate
Methotrexate 1,200 mg/m^2 in 250 mL D5W IV over 1 hour, followed by Methotrexate 3,000 mg/m^2 in 1,000 mL D5W by continuous infusion over 23 (+/-2) hours on Day 10 of Cycles 1 and 3, per study protocol.
Other Names:
  • MTX
Drug: Vincristine
Vincristine 1.5 mg/m^2 IV push (maximum of 2 mg) on Days 1 and 8 of Cycles 1 and 3, per study protocol.
Other Names:
  • Oncovin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of Progression-Free Survival (PFS)
Time Frame: Up to 8 years
Rate of Progression-Free Survival (PFS) in study participants. PFS is defined as the time from start of treatment to the earliest one of the following events: relapse (in patients who achieve complete response), disease progression (in patients with partial response or stable disease), or death. PFS will be evaluated by treating physician from staging Computed Tomography (CT) or Positron Emission Tomography (PET) scans.
Up to 8 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of Overall Survival (OS)
Time Frame: Up to 8 years
Rate of Overall Survival (OS) in study participants. OS is defined as the length of time from the start of treatment until death from any cause. OS will be evaluated by treating physician from staging CT or PET scans
Up to 8 years
Rate of Response to Protocol Therapy
Time Frame: Up to 8 years
Rate of response to protocol therapy in study participants. Response is defined as complete response (CR), complete response/unconfirmed (CRu) or partial response (PR) to protocol therapy according to criteria assignable to Non-Hodgkin's Lymphoma (NHL). Response assessment will be done by CT and Positron emission tomography (PET) scans, and bone marrow biopsy/aspirate, if clinically indicated.
Up to 8 years
Rate of Treatment-Related Toxicity in Study Participants
Time Frame: Up to 8 years
Rate of adverse events, serious adverse events and other toxicities related to protocol therapy in study participants, as evaluated by treating physician.
Up to 8 years

Collaborators and Investigators

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

Sponsor

University of Miami

Investigators

  • Principal Investigator: Izidore S. Lossos, MD, University of Miami

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 (Actual)

March 25, 2009

Primary Completion (Estimated)

September 1, 2024

Study Completion (Estimated)

September 1, 2027

Study Registration Dates

First Submitted

April 7, 2009

First Submitted That Met QC Criteria

April 7, 2009

First Posted (Estimated)

April 8, 2009

Study Record Updates

Last Update Posted (Actual)

August 2, 2023

Last Update Submitted That Met QC Criteria

July 31, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20080803
  • SCCC-2008043 (Other Identifier: University of Miami Sylvester Comprehensive Cancer Center)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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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