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

NCT ID: NCT00450801

Last Updated: 2015-11-10

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

22 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-04-30

Study Completion Date

2015-07-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Lymphoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Rituximab

Intervention Type DRUG

Rituximab 375 mg/m2 IV, Days 1 of all cycles

Cyclophosphamide

Intervention Type DRUG

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.

Cytarabine

Intervention Type DRUG

Cytarabine 2 grams/m2 IV every 12 hours x 4 doses, Days 1 and 2, Cycles 2 and 4.

Doxorubicin

Intervention Type DRUG

Doxorubicin 45 mg/m2 IV bolus, Day 1, Cycles 1 and 3

Etoposide

Intervention Type DRUG

Etoposide 60 mg/m2 IV daily x 5 days, Cycles 2 and 4

Ifosfamide

Intervention Type DRUG

Ifosfamide 1.5 grams/m2 IV once a day (QD) x 5 days, Cycles 2 and 4

Leucovorin

Intervention Type DRUG

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.

Methotrexate

Intervention Type DRUG

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.

Thalidomide

Intervention Type DRUG

Maintenance therapy.

Vincristine

Intervention Type DRUG

Vincristine 1.5 mg/m2 IVP (maximum of 2 mg), Day 1 and 8 , Cycles 1 and 3.

Mesna

Intervention Type DRUG

Mesna 360 mg/m2 IV every 3 hours x 5 days, Cycles 2 and 4

Filgrastim (G-CSF)

Intervention Type DRUG

G-CSF 480 mcg subcutaneous (SQ) starting Day 13 (Cycles 1 and 3), Day 7 (Cycles 2 and 4)

Granisetron

Intervention Type DRUG

Granisetron 1 mg IV on Day 1, Cycle 1 and 3

Decadron

Intervention Type DRUG

Decadron 10 mg IV on Day 1, Cycles 1 and 3

Interventions

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Rituximab

Rituximab 375 mg/m2 IV, Days 1 of all cycles

Intervention Type 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.

Intervention Type DRUG

Cytarabine

Cytarabine 2 grams/m2 IV every 12 hours x 4 doses, Days 1 and 2, Cycles 2 and 4.

Intervention Type DRUG

Doxorubicin

Doxorubicin 45 mg/m2 IV bolus, Day 1, Cycles 1 and 3

Intervention Type DRUG

Etoposide

Etoposide 60 mg/m2 IV daily x 5 days, Cycles 2 and 4

Intervention Type DRUG

Ifosfamide

Ifosfamide 1.5 grams/m2 IV once a day (QD) x 5 days, Cycles 2 and 4

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

Thalidomide

Maintenance therapy.

Intervention Type DRUG

Vincristine

Vincristine 1.5 mg/m2 IVP (maximum of 2 mg), Day 1 and 8 , Cycles 1 and 3.

Intervention Type DRUG

Mesna

Mesna 360 mg/m2 IV every 3 hours x 5 days, Cycles 2 and 4

Intervention Type DRUG

Filgrastim (G-CSF)

G-CSF 480 mcg subcutaneous (SQ) starting Day 13 (Cycles 1 and 3), Day 7 (Cycles 2 and 4)

Intervention Type DRUG

Granisetron

Granisetron 1 mg IV on Day 1, Cycle 1 and 3

Intervention Type DRUG

Decadron

Decadron 10 mg IV on Day 1, Cycles 1 and 3

Intervention Type DRUG

Other Intervention Names

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Rituxan Cytoxan AraC Adriamycin VP16 Ifex Folinic Acid amethopterin Thalomid Oncovin Mesnex Neupogen Sancuso Granisol Maxidex Ozurdex Baycadron

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Miami

OTHER

Sponsor Role lead

Responsible Party

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Izidore Lossos

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Izidore S. Lossos, MD

Role: STUDY_CHAIR

University of Miami Sylvester Comprehensive Cancer Center

Locations

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University of Miami Sylvester Comprehensive Cancer Center - Miami

Miami, Florida, United States

Site Status

Countries

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United States

References

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Lossos IS, Hosein PJ, Morgensztern D, Coleman F, Escalon MP, Byrne GE Jr, Rosenblatt JD, Walker GR. High rate and prolonged duration of complete remissions induced by rituximab, methotrexate, doxorubicin, cyclophosphamide, vincristine, ifosfamide, etoposide, cytarabine, and thalidomide (R-MACLO-IVAM-T), a modification of the National Cancer Institute 89-C-41 regimen, in patients with newly diagnosed mantle cell lymphoma. Leuk Lymphoma. 2010 Mar;51(3):406-14. doi: 10.3109/10428190903518345.

Reference Type RESULT
PMID: 20038221 (View on PubMed)

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 DERIVED
PMID: 33735476 (View on PubMed)

Other Identifiers

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SCCC-2003027

Identifier Type: OTHER

Identifier Source: secondary_id

WIRB-20051242

Identifier Type: OTHER

Identifier Source: secondary_id

20030165

Identifier Type: -

Identifier Source: org_study_id

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