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

NCT00878254 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 20080803SCCC-2008043
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Mantle-Cell Lymphoma

Keywords

Non-Hodgkin's Lymphoma

Outcome Measures

Primary Outcomes (2)

• Progression-Free Survival (PFS)

  Progression-Free Survival (PFS) among study participants. PFS is defined as the time in years 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 12 years

• Progression-Free Survival (PFS) Rate at 5 Years Using Kaplan-Meier Method

  Progression-Free Survival (PFS) rate at 5 years estimated by the Kaplan-Meier method will be reported as percentage probability of participants alive without relapse or disease progression at 5 years after starting study therapy. 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.

  5 years

Secondary Outcomes (4)

• Overall Survival (OS) Rate at 5 Years Using Kaplan-Meier Method

  5 years

• Rate of Response to Study Therapy

  Up to 8 years

• Number of Participants Experiencing Treatment-Related Serious Adverse Events During R-MACLO/IVAM Induction Therapy

  Up to 4 months

• Number of Participants Experiencing Treatment-Related Adverse Events During R-MACLO/IVAM Induction Therapy

  Up to 4 months

Study Arms (1)

R-MACLO/IVAM Group

EXPERIMENTAL

Participants in this group will receive four 21-day cycles of combination R-MACLO/IVAM induction therapy, followed by Rituximab maintenance therapy as follows: Induction Therapy: * Cycles 1 and 3: Rituximab, Doxorubicin, Vincristine, Cyclophosphamide, Methotrexate, Leucovorin and Granulocyte-colony stimulating factor (G-CSF) * Cycles 2 and 4: Rituximab, Cytarabine, Ifosfamide, Mesna, Etoposide, and G-CSF. Maintenance Therapy: Rituximab: For study participants in complete remission. Every 6 months for up to 3 years. Total participation duration is about 4 years. Participants will be followed for survival.

Biological: G-CSF; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Doxorubicin; Drug: Etoposide; Drug: Ifosfamide; Drug: Leucovorin; Drug: Mesna; Drug: Methotrexate; Drug: Vincristine

Interventions

G-CSF BIOLOGICAL

Granulocyte-colony stimulating factor (G-CSF) 480 mcg subcutaneously starting on Day 13 of Cycles 1 and 3; and Day 7 of Cycles 2 and 4.

Also known as: Filgrastim, Neupogen

R-MACLO/IVAM Group

Rituximab DRUG

Rituximab 375 mg/m\^2 intravenously (IV) on Day 1 for 4 Cycles during induction therapy. Participants achieving complete remission will then receive Rituximab maintenance therapy every 6 months for up to three years.

Also known as: Rituxan

R-MACLO/IVAM Group

Cyclophosphamide DRUG

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.

Also known as: Cytoxan

R-MACLO/IVAM Group

Cytarabine DRUG

Cytarabine (AraC) 2 grams/m\^2 IV on Days 1 and 2 of Cycles 2 and 4.

Also known as: AraC

R-MACLO/IVAM Group

Doxorubicin DRUG

Doxorubicin 45 mg/m\^2 IV bolus on Day 1 of Cycles 1 and 3.

Also known as: Adriamycin

R-MACLO/IVAM Group

Etoposide DRUG

Etoposide (VP16) 60 mg/m\^2 IV on Days 1 through 5 of Cycles 2 and 4.

Also known as: VP16

R-MACLO/IVAM Group

Ifosfamide DRUG

Ifosfamide 1.5 grams/m\^2 IV on Days 1 through 5 of Cycles 2 and 4.

Also known as: Ifex

R-MACLO/IVAM Group

Leucovorin DRUG

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.

Also known as: Folinic acid

R-MACLO/IVAM Group

Mesna DRUG

Mesna 360 mg/m\^2 IV on Days 1 through 5 of Cycles 2 and 4.

Also known as: Mesnex

R-MACLO/IVAM Group

Methotrexate DRUG

Methotrexate (MTX) 1,200 mg/m\^2 in 250 mL with Dextrose 5% in water (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.

Also known as: MTX

R-MACLO/IVAM Group

Vincristine DRUG

Vincristine 1.5 mg/m\^2 IV push (maximum of 2 mg) on Days 1 and 8 of Cycles 1 and 3.

Also known as: Oncovin

R-MACLO/IVAM Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Previously untreated, histologically confirmed mantle cell lymphoma,
• Measurable or evaluable disease (at least one site with \>1.5 cm in diameter
• 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 (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
• 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.

You may not qualify if:

• Previous chemotherapy, immunotherapy or radiotherapy for this mantle cell 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 human immunodeficiency virus (HIV) or Acquired Immunodeficiency Syndrome (AIDS).
• Presence of hepatitis or hepatitis B virus (HBV) infection.
• Pregnant or breast-feeding women.
• Central Nervous System (CNS) involvement.

Sponsors & Collaborators

• University of Miami: lead

Study Sites (1)

University of Miami

Miami, Florida, 33186, United States

Location

Related Publications (1)

• 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.

  PMID: 33735476 RESULT

MeSH Terms

Conditions

Lymphoma, Mantle-Cell; Lymphoma, Non-Hodgkin

Interventions

Granulocyte Colony-Stimulating Factor; Filgrastim; Rituximab; Cyclophosphamide; Cytarabine; Doxorubicin; Etoposide; Ifosfamide; Leucovorin; Mesna; Methotrexate; Vincristine

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Oxazines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Aminopterin; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Results Point of Contact

• Title: Izidore Lossos MD
• Organization: University of Miami

ilossos@med.miami.edu

+1 (305) 2434785

Study Officials

• Izidore S. Lossos, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 7, 2009
• First Posted: April 8, 2009
• Study Start: March 25, 2009
• Primary Completion: June 28, 2024
• Study Completion: May 30, 2025
• Last Updated: July 23, 2025
• Results First Posted: July 23, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)