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

NCT ID: NCT00878254

Last Updated: 2025-07-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-03-25
• Study Completion Date: 2025-05-30

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

R-MACLO/IVAM Group

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.

Group Type: EXPERIMENTAL

G-CSF

Intervention Type: 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.

Rituximab

Intervention Type: 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.

Cyclophosphamide

Intervention Type: 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.

Cytarabine

Intervention Type: DRUG

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

Doxorubicin

Intervention Type: DRUG

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

Etoposide

Intervention Type: DRUG

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

Ifosfamide

Intervention Type: DRUG

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

Leucovorin

Intervention Type: 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.

Mesna

Intervention Type: DRUG

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

Methotrexate

Intervention Type: 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.

Vincristine

Intervention Type: DRUG

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

Interventions

G-CSF

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.

Intervention Type: BIOLOGICAL

Rituximab

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.

Intervention Type: 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.

Intervention Type: DRUG

Cytarabine

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

Intervention Type: DRUG

Doxorubicin

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

Intervention Type: DRUG

Etoposide

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

Intervention Type: DRUG

Ifosfamide

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

Intervention Type: 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.

Intervention Type: DRUG

Mesna

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

Intervention Type: DRUG

Methotrexate

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.

Intervention Type: DRUG

Vincristine

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

Intervention Type: DRUG

Other Intervention Names

Filgrastim; Neupogen; Rituxan; Cytoxan; AraC; Adriamycin; VP16; Ifex; Folinic acid; Mesnex; MTX; Oncovin

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Miami

OTHER

Sponsor Role: lead

Responsible Party

Izidore Lossos, MD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Izidore S. Lossos, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Locations

University of Miami

Miami, Florida, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 33735476 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

SCCC-2008043

Identifier Type: OTHER

Identifier Source: secondary_id

20080803

Identifier Type: -

Identifier Source: org_study_id