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R-MACLO-IVAM and Thalidomide in Untreated Mantle Cell Lymphoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Izidore Lossos, University of Miami
ClinicalTrials.gov Identifier:
NCT00450801
First received: March 20, 2007
Last updated: October 12, 2015
Last verified: October 2015
  Purpose

RATIONALE: To evaluate the efficacy of a new high intensity chemotherapy regimen with thalidomide maintenance in patients with newly diagnosed mantle cell lymphoma

PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy followed by thalidomide works in treating patients with previously untreated mantle cell lymphoma.


Condition Intervention Phase
Lymphoma
Drug: Rituximab
Drug: Cyclophosphamide
Drug: Cytarabine
Drug: Doxorubicin
Drug: Etoposide
Drug: Ifosfamide
Drug: Leucovorin
Drug: Methotrexate
Drug: Thalidomide
Drug: Vincristine
Drug: Mesna
Drug: Filgrastim (G-CSF)
Drug: Granisetron
Drug: Decadron
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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 (MACLO/IVAM) in Patients With Previously Untreated Mantle Cell Lymphoma

Resource links provided by NLM:


Further study details as provided by University of Miami:

Primary Outcome Measures:
  • Progression-free Survival Rate [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Percentage of participants achieving progression-free survival at 1, 3 and 5 years after the start of protocol therapy, based upon the International Working Group Response Criteria for Non-Hodgkin's Lymphoma (NHL). Progression is defined as a ≥ 50% increase from nadir in the product of the two largest perpendicular diameters (PPD-size) of any previously identified abnormal node, or appearance of any new lesion.


Secondary Outcome Measures:
  • Overall Survival Rate [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Percentage of participants who are alive up to five years after receipt of protocol therapy.

  • Response Rate [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Percentage of participants achieving complete response (CR) to protocol therapy according to International Working Group Response Criteria for Non-Hodgkin's Lymphoma (NHL) using the CT imaging method. Patients were classified by best tumor response; CR was defined as normalization of the lactate dehydrogenase (LDH), complete disappearance of disease-related symptoms and lymph nodes, and clearance of lymphoma from involved organs; complete response unconfirmed (CRu) as a residual lymph node greater than 1.5 cm in greatest transverse diameter that had regressed by more than 75% or an indeterminate bone marrow examination; partial response (PR) as greater than 50% reduction in the involved lymph nodes, or disappearance of the involved lymph nodes but persistent bone marrow involvement; relapse/progression as new or increased lymph nodes, organomegaly, or reappearance of bone marrow involvement.

  • Number of Patients Experiencing Adverse Events. [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    Number of patients experiencing adverse events during the course of protocol therapy.


Enrollment: 22
Study Start Date: April 2004
Study Completion Date: July 2015
Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: R-MACLO-IVAM-T
Rituximab, Methotrexate, Doxorubicin, Cyclophosphamide and Vincristine (cycle 1), followed by Rituximab, Ifosfamide (and Mesna), Etoposide and Cytarabine (cycle 2). These two cycles are repeated once, and patients achieving complete repose receive maintenance Thalidomide.
Drug: Rituximab
Rituximab 375 mg/m2 IV, Days 1 of all cycles
Other Name: Rituxan
Drug: Cyclophosphamide
Cyclophosphamide 800 mg/m2 IV, Day 1, Cyclophosphamide 200 mg/m2 IV Days 2 - 5, Cycles 1 and 3. Cyclophosphamide will be given in 100 cc NS IV over 30 minutes.
Other Name: Cytoxan
Drug: Cytarabine
Cytarabine 2 grams/m2 IV every 12 hours x 4 doses, Days 1 and 2, Cycles 2 and 4.
Other Name: AraC
Drug: Doxorubicin
Doxorubicin 45 mg/m2 IV bolus, Day 1, Cycles 1 and 3
Other Name: Adriamycin
Drug: Etoposide
Etoposide 60 mg/m2 IV daily x 5 days, Cycles 2 and 4
Other Name: VP16
Drug: Ifosfamide
Ifosfamide 1.5 grams/m2 IV once a day (QD) x 5 days, Cycles 2 and 4
Other Name: Ifex
Drug: Leucovorin
Leucovorin 180 mg/m2 IV beginning 36 hours after start of methotrexate infusion and then 12 mg/m2 IV every 6 hours until methotrexate level is below 0.01 nM. Day 10, Cycles 1 and 3.
Other Name: Folinic Acid
Drug: Methotrexate
Methotrexate 1,200 mg/m2 in 250 cc 5 percent dextrose in water (D5W) IV over 1 hour followed by Methotrexate 5,520 mg/m2 in 1,000 cc D5W by continuous infusion over 23 hours (240 mg/m2 every hour for 23 hours). Day 10, Cycles 1 and 3.
Other Name: amethopterin
Drug: Thalidomide
Maintenance therapy.
Other Name: Thalomid
Drug: Vincristine
Vincristine 1.5 mg/m2 IVP (maximum of 2 mg), Day 1 and 8 , Cycles 1 and 3.
Other Name: Oncovin
Drug: Mesna
Mesna 360 mg/m2 IV every 3 hours x 5 days, Cycles 2 and 4
Other Name: Mesnex
Drug: Filgrastim (G-CSF)
G-CSF 480 mcg subcutaneous (SQ) starting Day 13 (Cycles 1 and 3), Day 7 (Cycles 2 and 4)
Other Name: Neupogen
Drug: Granisetron
Granisetron 1 mg IV on Day 1, Cycle 1 and 3
Other Names:
  • Sancuso
  • Granisol
Drug: Decadron
Decadron 10 mg IV on Day 1, Cycles 1 and 3
Other Names:
  • Maxidex
  • Ozurdex
  • Baycadron

Detailed Description:

OBJECTIVES:

Primary

  • Determine the progression-free survival of patients with previously untreated mantle cell lymphoma treated rituximab in combination with methotrexate, doxorubicin, cyclophosphamide, leucovorin, vincristine, ifosfamide, etoposide, cytarabine and mesna (MACLO/IVAM) followed by thalidomide.

Secondary

  • Determine the overall survival of patients treated with this regimen.
  • Determine the response rate in patients treated with this regimen.
  • Determine the toxicity of this regimen in these patients.

OUTLINE: During cycle 1, patients will receive rituximab intravenous (IV), granisetron IV, decadron IV, doxorubicin IV bolus, vincristine intravenous pyelogram (IVP) on day 1; cyclophosphamide IV on day 1-5; vincristine IVP on day 8; methotrexate IV, methotrexate by continuous infusion, then leucovorin IV until methotrexate level is below 0.01 nanomolar (nM) on day 10. Patients will receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 13 and continuing until blood counts recover.

When absolute neutrophil count (ANC) reaches1,500/mm^3, patients will start cycle 2. Patients will receive rituximab IV on day 1; cytarabine IV on day 1 and 2; ifosfamide IV, mesna IV, etoposide IV on day 1-5; and G-CSF SC daily beginning on day 7 and continuing until ANC is greater than 1,000 cells/mm^3.

Approximately 2-3 weeks later, patients receive another course of therapy as above.After cycle 4, patients in complete remission will take oral thalidomide until progression of disease. After completion of study treatment, patients are followed monthly for 3 months, every 3 months for 2 years, every 6 months for 3-5 years, and then annually thereafter or at study termination.

PROJECTED ACCRUAL: A total of 22 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Previously untreated, histologically confirmed mantle cell lymphoma.
  • Measurable or evaluable disease.
  • 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 (SGOT and/or 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 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 HIV or AIDS
  • Presence of hepatitis or hepatitis B virus (HBV) infection
  • Pregnant or breast-feeding women.
  • Central nervous system (CNS) involvement
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00450801

Locations
United States, Florida
University of Miami Sylvester Comprehensive Cancer Center - Miami
Miami, Florida, United States, 33136
Sponsors and Collaborators
University of Miami
Investigators
Study Chair: Izidore S. Lossos, MD University of Miami Sylvester Comprehensive Cancer Center
  More Information

Publications:
Responsible Party: Izidore Lossos, Professor, University of Miami
ClinicalTrials.gov Identifier: NCT00450801     History of Changes
Other Study ID Numbers: 20030165  SCCC-2003027  WIRB-20051242 
Study First Received: March 20, 2007
Results First Received: August 7, 2015
Last Updated: October 12, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Miami:
contiguous stage II mantle cell lymphoma
noncontiguous stage II mantle cell lymphoma
stage I mantle cell lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma

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
Thalidomide
Cytarabine
Rituximab
Ifosfamide
Isophosphamide mustard
Liposomal doxorubicin
Etoposide phosphate
Doxorubicin
Vincristine
Etoposide
Dexamethasone
BB 1101
Mesna
Granisetron
Dexamethasone acetate
Dexamethasone 21-phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 30, 2016