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

Primary Purpose

Mantle-Cell Lymphoma

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
G-CSF
Rituximab
Cyclophosphamide
Cytarabine
Doxorubicin
Etoposide
Ifosfamide
Leucovorin
Mesna
Methotrexate
Vincristine
Sponsored by
University of Miami
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mantle-Cell Lymphoma focused on measuring Non-Hodgkin's Lymphoma, MCL, NHL

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Miami

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

R-MACLO/IVAM

Arm Description

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.

Outcomes

Primary Outcome Measures

Rate of Progression-Free Survival (PFS)
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.

Secondary Outcome Measures

Rate of Overall Survival (OS)
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
Rate of Response to Protocol Therapy
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.
Rate of Treatment-Related Toxicity in Study Participants
Rate of adverse events, serious adverse events and other toxicities related to protocol therapy in study participants, as evaluated by treating physician.

Full Information

First Posted
April 7, 2009
Last Updated
July 31, 2023
Sponsor
University of Miami
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1. Study Identification

Unique Protocol Identification Number
NCT00878254
Brief Title
Rituximab and Combination Chemotherapy in Treating Patients With Previously Untreated Mantle Cell Lymphoma
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 25, 2009 (Actual)
Primary Completion Date
September 2024 (Anticipated)
Study Completion Date
September 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Miami

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mantle-Cell Lymphoma
Keywords
Non-Hodgkin's Lymphoma, MCL, NHL

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
R-MACLO/IVAM
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
G-CSF
Other Intervention Name(s)
Filgrastim, Neupogen
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Rituxan
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Other Intervention Name(s)
AraC
Intervention Description
Cytarabine 2 grams/m^2 IV on Days 1 and 2 of Cycles 2 and 4, per study protocol.
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Other Intervention Name(s)
Adriamycin
Intervention Description
Doxorubicin 45 mg/m^2 IV bolus Day 1 of Cycles 1 and 3, per study protocol.
Intervention Type
Drug
Intervention Name(s)
Etoposide
Other Intervention Name(s)
VP16
Intervention Description
Etoposide 60 mg/m^2 IV on Days 1 through 5 of Cycles 2 and 4, per study protocol.
Intervention Type
Drug
Intervention Name(s)
Ifosfamide
Other Intervention Name(s)
Ifex
Intervention Description
Ifosfamide 1.5 grams/m^2 IV on Days 1 through 5 of Cycles 2 and 4, per study protocol.
Intervention Type
Drug
Intervention Name(s)
Leucovorin
Other Intervention Name(s)
Folinic acid
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Mesna
Other Intervention Name(s)
Mesnex
Intervention Description
Mesna 360 mg/m^2 IV on Days 1 through 5 of Cycles 2 and 4, per study protocol.
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Other Intervention Name(s)
MTX
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Vincristine
Other Intervention Name(s)
Oncovin
Intervention Description
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.
Primary Outcome Measure Information:
Title
Rate of Progression-Free Survival (PFS)
Description
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.
Time Frame
Up to 8 years
Secondary Outcome Measure Information:
Title
Rate of Overall Survival (OS)
Description
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
Time Frame
Up to 8 years
Title
Rate of Response to Protocol Therapy
Description
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.
Time Frame
Up to 8 years
Title
Rate of Treatment-Related Toxicity in Study Participants
Description
Rate of adverse events, serious adverse events and other toxicities related to protocol therapy in study participants, as evaluated by treating physician.
Time Frame
Up to 8 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Izidore S. Lossos, MD
Organizational Affiliation
University of Miami
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33186
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33735476
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.
Results Reference
derived

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

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