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

This study is currently recruiting participants.
Verified August 2017 by Izidore Lossos, University of Miami
Sponsor:
ClinicalTrials.gov Identifier:
NCT00878254
First Posted: April 8, 2009
Last Update Posted: August 21, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Izidore Lossos, University of Miami
  Purpose
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).

Condition Intervention Phase
Mantle-Cell Lymphoma Biological: G-CSF Drug: Rituximab Drug: Cyclophosphamide Drug: Cytarabine Drug: Doxorubicin Drug: Etoposide Drug: Ifosfamide Drug: Leucovorin Drug: Mesna Drug: Methotrexate Drug: Vincristine Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Izidore Lossos, University of Miami:

Primary Outcome Measures:
  • Rate of Progression-Free Survival (PFS) [ Time Frame: 6, 12, 18 and 24 months Post-Treatment ]
    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.


Secondary Outcome Measures:
  • Rate of Overall Survival (OS) [ Time Frame: 6, 12, 18 and 24 months Post-Treatment ]
    Rate of Overall Survival (OS) in study participants. Overall survival is defined as the length of time from the start of treatment until death from any cause.

  • Rate of Response to Protocol Therapy [ Time Frame: End of Cycles 2 and 4, End of Treatment, Up to 5 years Post-Treatment ]
    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 [ Time Frame: Up to the End of Protocol Therapy ]
    Rate of adverse events, serious adverse events and other toxicities related to protocol therapy in study participants.


Estimated Enrollment: 22
Actual Study Start Date: March 25, 2009
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: Cytoxan
Drug: Cytarabine
Cytarabine 2 grams/m^2 IV on Days 1 and 2 of Cycles 2 and 4, per study protocol.
Other Name: AraC
Drug: Doxorubicin
Doxorubicin 45 mg/m^2 IV bolus Day 1 of Cycles 1 and 3, per study protocol.
Other Name: Adriamycin
Drug: Etoposide
Etoposide 60 mg/m^2 IV on Days 1 through 5 of Cycles 2 and 4, per study protocol.
Other Name: VP16
Drug: Ifosfamide
Ifosfamide 1.5 grams/m^2 IV on Days 1 through 5 of Cycles 2 and 4, per study protocol.
Other Name: 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 Name: Folinic acid
Drug: Mesna
Mesna 360 mg/m^2 IV on Days 1 through 5 of Cycles 2 and 4, per study protocol.
Other Name: 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 Name: 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 Name: Oncovin

Detailed Description:

This is a phase 2 study of Rituximab in combination with Methotrexate, Doxorubicin, Cyclophosphamide, Leucovorin, Vincristine, Ifosfamide, Etoposide, Cytarabine and Mesna (R-MACLO/IVAM) in subjects with previously untreated Mantle Cell Lymphoma (MCL). Treatment will consist of up to 4 cycles of therapy. Response assessment by CT and PET scans will be performed post Cycle 2. Once the final cycle of therapy is completed, response evaluation will be performed based on pre-study CT scans, PET/ Scan/endoscopy or any staging scans that were positive at baseline. (PI approval required if treating with less than 4 cycles).

Subjects in complete remission will be given Rituximab per institution guidelines, as 4 weekly doses every 6 months for a total of 3 years, or until progression of disease, or if the subject is unable to tolerate further treatment. Rituximab should begin 6 months from date of discharge +/- 21 days. Maintenance therapy, premedications can be changed based on clinical consideration from treating physician. Timelines for giving premedications are given per institutional guidelines. Subject may be discharged after administration of Rituximab, once stable.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   19 Years to 72 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00878254


Locations
United States, Florida
University of Miami Recruiting
Miami, Florida, United States, 33186
Contact: Izidore S. Lossos, MD    305-243-4785    ilossos@med.miami.edu   
Principal Investigator: Izidore S Lossos, MD         
Sponsors and Collaborators
University of Miami
Investigators
Principal Investigator: Izidore S. Lossos, MD University of Miami
  More Information

Responsible Party: Izidore Lossos, Professor, University of Miami
ClinicalTrials.gov Identifier: NCT00878254     History of Changes
Other Study ID Numbers: 20080803
SCCC-2008043 ( Other Identifier: University of Miami Sylvester Comprehensive Cancer Center )
First Submitted: April 7, 2009
First Posted: April 8, 2009
Last Update Posted: August 21, 2017
Last Verified: August 2017

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

Keywords provided by Izidore Lossos, University of Miami:
Mantle Cell Lymphoma
Non-Hodgkin's Lymphoma
MCL
NHL

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cyclophosphamide
Methotrexate
Cytarabine
Rituximab
Ifosfamide
Isophosphamide mustard
Liposomal doxorubicin
Etoposide phosphate
Doxorubicin
Etoposide
Vincristine
Mesna
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists