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

NCT00450801 | Completed Phase 2 Results DMC

• 3 other identifiers: 20030165SCCC-2003027WIRB-20051242
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Lymphoma

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival Rate

  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.

  Up to 5 years

Secondary Outcomes (3)

• Overall Survival Rate

  Up to 5 years

• Response Rate

  Up to 5 years

• Number of Patients Experiencing Adverse Events.

  Up to 5 years

Study Arms (1)

R-MACLO-IVAM-T

EXPERIMENTAL

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; 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

Interventions

Rituximab DRUG

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

Also known as: Rituxan

R-MACLO-IVAM-T

Cyclophosphamide 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.

Also known as: Cytoxan

R-MACLO-IVAM-T

Cytarabine DRUG

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

Also known as: AraC

R-MACLO-IVAM-T

Doxorubicin DRUG

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

Also known as: Adriamycin

R-MACLO-IVAM-T

Etoposide DRUG

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

Also known as: VP16

R-MACLO-IVAM-T

Ifosfamide DRUG

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

Also known as: Ifex

R-MACLO-IVAM-T

Leucovorin 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.

Also known as: Folinic Acid

R-MACLO-IVAM-T

Methotrexate 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.

Also known as: amethopterin

R-MACLO-IVAM-T

Thalidomide DRUG

Maintenance therapy.

Also known as: Thalomid

R-MACLO-IVAM-T

Vincristine DRUG

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

Also known as: Oncovin

R-MACLO-IVAM-T

Mesna DRUG

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

Also known as: Mesnex

R-MACLO-IVAM-T

Filgrastim (G-CSF) DRUG

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

Also known as: Neupogen

R-MACLO-IVAM-T

Granisetron DRUG

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

Also known as: Sancuso, Granisol

R-MACLO-IVAM-T

Decadron DRUG

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

Also known as: Maxidex, Ozurdex, Baycadron

R-MACLO-IVAM-T

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Miami: lead

Study Sites (1)

University of Miami Sylvester Comprehensive Cancer Center - Miami

Miami, Florida, 33136, United States

Location

Related Publications (2)

• 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.

  PMID: 20038221 RESULT

• 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.

  PMID: 33735476 DERIVED

MeSH Terms

Conditions

Lymphoma; Lymphoma, Mantle-Cell

Interventions

Rituximab; Cyclophosphamide; Cytarabine; Doxorubicin; Etoposide; Ifosfamide; Leucovorin; Methotrexate; Thalidomide; Vincristine; Mesna; Filgrastim; Granulocyte Colony-Stimulating Factor; Granisetron; Calcium Dobesilate; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Oxazines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Aminopterin; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Azabicyclo Compounds; Aza Compounds; Indazoles; Pyrazoles; Azoles; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring; Benzenesulfonates; Benzene Derivatives; Arylsulfonates; Arylsulfonic Acids; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Izidore Lossos MD
• Organization: University of Miami

ilossos@med.miami.edu

305-243-4785

Study Officials

• Izidore S. Lossos, MD

  University of Miami Sylvester Comprehensive Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 20, 2007
• First Posted: March 22, 2007
• Study Start: April 1, 2004
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: November 10, 2015
• Results First Posted: November 10, 2015

Record last verified: 2015-10

Locations

US (1)