Mantle-Cell LymphomaPhase 2NCT00878254
Rituximab and Combination Chemotherapy in Treating Patients With Previously Untreated Mantle Cell Lymphoma
A Phase 2 study testing G-CSF, Rituximab and Cyclophosphamide in people with Mantle-Cell Lymphoma, run by University of Miami at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mantle-Cell Lymphoma
- What is being tested?
- G-CSF, Rituximab and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Mar 2009to 30 May 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
Show all 12Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Study of Rituximab in Combination With Methotrexate, Doxorubicin, Cyclophosphamide, Leucovorin, Vincristine, Ifosfamide, Etoposide, Cytarabine and Mesna (R-MACLO/IVAM) in Patients With Previously Untreated Mantle Cell Lymphoma
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).
- Conditions
- Mantle-Cell Lymphoma
- Being tested
- G-CSF, Rituximab, Cyclophosphamide, Cytarabine, Doxorubicin
- Keywords
- Non-Hodgkin's Lymphoma
- Medical subject headings
- Lymphoma, Mantle-Cell, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
G-CSFBiological
Also called Filgrastim, Neupogen
Granulocyte-colony stimulating factor (G-CSF) 480 mcg subcutaneously starting on Day 13 of Cycles 1 and 3; and Day 7 of Cycles 2 and 4.
RituximabDrug
Also called Rituxan
Rituximab 375 mg/m^2 intravenously (IV) on Day 1 for 4 Cycles during induction therapy. Participants achieving complete remission will then receive Rituximab maintenance therapy every 6 months for up to three years.
CyclophosphamideDrug
Also called Cytoxan
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.
CytarabineDrug
Also called AraC
Cytarabine (AraC) 2 grams/m^2 IV on Days 1 and 2 of Cycles 2 and 4.
DoxorubicinDrug
Also called Adriamycin
Doxorubicin 45 mg/m^2 IV bolus on Day 1 of Cycles 1 and 3.
EtoposideDrug
Also called VP16
Etoposide (VP16) 60 mg/m^2 IV on Days 1 through 5 of Cycles 2 and 4.
IfosfamideDrug
Also called Ifex
Ifosfamide 1.5 grams/m^2 IV on Days 1 through 5 of Cycles 2 and 4.
LeucovorinDrug
Also called Folinic acid
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.
MesnaDrug
Also called Mesnex
Mesna 360 mg/m^2 IV on Days 1 through 5 of Cycles 2 and 4.
MethotrexateDrug
Also called MTX
Methotrexate (MTX) 1,200 mg/m^2 in 250 mL with Dextrose 5% in water (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.
VincristineDrug
Also called Oncovin
Vincristine 1.5 mg/m^2 IV push (maximum of 2 mg) on Days 1 and 8 of Cycles 1 and 3.
| Study group | Role | What they receive |
|---|---|---|
| R-MACLO/IVAM Group | Experimental | Participants in this group will receive four 21-day cycles of combination R-MACLO/IVAM induction therapy, followed by Rituximab maintenance therapy as follows:
Induction Therapy:
* Cycles 1 and 3: Rituximab, Doxorubicin, Vincristine, Cyclophosphamide, Methotrexate, Leucovorin and Granulocyte-colony stimulating factor (G-CSF)
* Cycles 2 and 4: Rituximab, Cytarabine, Ifosfamide, Mesna, Etoposide, and G-CSF.
Maintenance Therapy: Rituximab: For study participants in complete remission. Every 6 months for up to 3 years.
Total participation duration is about 4 years. Participants will be followed for survival. Receives: Biological: G-CSF; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Doxorubicin; Drug: Etoposide; Drug: Ifosfamide; Drug: Leucovorin; Drug: Mesna; Drug: Methotrexate; Drug: Vincristine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-Free Survival (PFS)
Progression-Free Survival (PFS) among study participants. PFS is defined as the time in years 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.
Measured: Up to 12 years
Progression-Free Survival (PFS) Rate at 5 Years Using Kaplan-Meier Method
Progression-Free Survival (PFS) rate at 5 years estimated by the Kaplan-Meier method will be reported as percentage probability of participants alive without relapse or disease progression at 5 years after starting study therapy. 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.
Measured: 5 years
Secondary outcomes (4)
Overall Survival (OS) Rate at 5 Years Using Kaplan-Meier Method
Overall Survival (OS) rate at 5 years estimated by the Kaplan-Meier method will be reported as percentage probability of survival beyond 5 years. OS is defined as elapsed time from start date of treatment to date of death from any cause. Alive participants will be censored at last date known to be alive.
Measured: 5 years
Rate of Response to Study Therapy
The rate of response to study therapy will be reported as the number of participants achieving 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.
Measured: Up to 8 years
Number of Participants Experiencing Treatment-Related Serious Adverse Events During R-MACLO/IVAM Induction Therapy
The number of participants experiencing treatment-related serious adverse events (SAEs) during R-MACLO/IVAM induction therapy. AEs and SAEs will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 3.0, as evaluated by treating physician.
Measured: Up to 4 months
Number of Participants Experiencing Treatment-Related Adverse Events During R-MACLO/IVAM Induction Therapy
The number of participants experiencing treatment-related adverse events (AEs) during R-MACLO/IVAM induction therapy. AEs and SAEs will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 3.0, as evaluated by treating physician.
Measured: Up to 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2009 (estimated)
- Study start25 Mar 2009
- Primary completion28 Jun 2024
- Study completion30 May 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Mantle-Cell LymphomaStudies of the same condition, open and under way.
- More trials run by University of MiamiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Miami
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Izidore Lossos, MD, University of Miami
- Investigators
- Izidore S. Lossos, MD, Principal investigator, University of Miami
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00878254
- Sponsor's protocol ID
- 20080803
- Other IDs
- SCCC-2008043
- Status last verified
- Jul 2025
- First submitted
- 7 Apr 2009
- Last updated
- 23 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 33735476
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Rituximab in Combination With Methotrexate, Doxorubicin, Cyclophosphamide, Leucovorin, Vincristine, Ifosfamide, Etoposide, Cytarabine and Mesna (R-MACLO/IVAM) in Patients With Previously Untreated Mantle Cell Lymphoma
- ClinicalTrials.gov ID
- NCT00878254
- Acronym / sponsor ID
- 20080803
- Conditions
- Mantle-Cell Lymphoma
- Keywords
- Non-Hodgkin's Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- University of MiamiUniversity, hospital or other
- Study start
- 25 Mar 2009 (actual)
- Primary completion
- 28 Jun 2024 (actual)
- Study completion
- 30 May 2025 (actual)
- First posted
- 8 Apr 2009 (estimated)
- Results
- Posted 23 Jul 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| R-MACLO/IVAM Group | Experimental | Biological: G-CSF, Drug: Rituximab, Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Doxorubicin, Drug: Etoposide, Drug: Ifosfamide, Drug: Leucovorin, Drug: Mesna, Drug: Methotrexate, Drug: VincristineParticipants in this group will receive four 21-day cycles of combination R-MACLO/IVAM induction therapy, followed by Rituximab maintenance therapy as follows: Induction Therapy: * Cycles 1 and 3: Rituximab, Doxorubicin, Vincristine, Cyclophosphamide, Methotrexate, Leucovorin and Granulocyte-colony stimulating factor (G-CSF) * Cycles 2 and 4: Rituximab, Cytarabine, Ifosfamide, Mesna, Etoposide, and G-CSF. Maintenance Therapy: Rituximab: For study participants in complete remission. Every 6 months for up to 3 years. Total participation duration is about 4 years. Participants will be followed for survival. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (8 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| G-CSFAlso: Filgrastim, NeupogenGranulocyte-colony stimulating factor (G-CSF) 480 mcg subcutaneously starting on Day 13 of Cycles 1 and 3; and Day 7 of Cycles 2 and 4. | Biological | R-MACLO/IVAM Group |
| RituximabAlso: RituxanRituximab 375 mg/m^2 intravenously (IV) on Day 1 for 4 Cycles during induction therapy. Participants achieving complete remission will then receive Rituximab maintenance therapy every 6 months for up to three years. | Drug | R-MACLO/IVAM Group |
| CyclophosphamideAlso: CytoxanCyclophosphamide 800 mg/m^2 IV on Day 1 and 200 mg/m^2 IV on Days 2 through 5 of Cycles 1 and 3. | Drug | R-MACLO/IVAM Group |
| CytarabineAlso: AraCCytarabine (AraC) 2 grams/m^2 IV on Days 1 and 2 of Cycles 2 and 4. | Drug | R-MACLO/IVAM Group |
| DoxorubicinAlso: AdriamycinDoxorubicin 45 mg/m^2 IV bolus on Day 1 of Cycles 1 and 3. | Drug | R-MACLO/IVAM Group |
| EtoposideAlso: VP16Etoposide (VP16) 60 mg/m^2 IV on Days 1 through 5 of Cycles 2 and 4. | Drug | R-MACLO/IVAM Group |
| IfosfamideAlso: IfexIfosfamide 1.5 grams/m^2 IV on Days 1 through 5 of Cycles 2 and 4. | Drug | R-MACLO/IVAM Group |
| LeucovorinAlso: Folinic acidLeucovorin 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. | Drug | R-MACLO/IVAM Group |
| MesnaAlso: MesnexMesna 360 mg/m^2 IV on Days 1 through 5 of Cycles 2 and 4. | Drug | R-MACLO/IVAM Group |
| MethotrexateAlso: MTXMethotrexate (MTX) 1,200 mg/m^2 in 250 mL with Dextrose 5% in water (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. | Drug | R-MACLO/IVAM Group |
| VincristineAlso: OncovinVincristine 1.5 mg/m^2 IV push (maximum of 2 mg) on Days 1 and 8 of Cycles 1 and 3. | Drug | R-MACLO/IVAM Group |
Primary outcome
Progression-Free Survival (PFS)
Time frame: Up to 12 years
Progression-Free Survival (PFS) among study participants. PFS is defined as the time in years 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.
Progression-Free Survival (PFS) Rate at 5 Years Using Kaplan-Meier Method
Time frame: 5 years
Progression-Free Survival (PFS) rate at 5 years estimated by the Kaplan-Meier method will be reported as percentage probability of participants alive without relapse or disease progression at 5 years after starting study therapy. 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.
4 secondary outcomes
Overall Survival (OS) Rate at 5 Years Using Kaplan-Meier Method
Time frame: 5 years
Rate of Response to Study Therapy
Time frame: Up to 8 years
Number of Participants Experiencing Treatment-Related Serious Adverse Events During R-MACLO/IVAM Induction Therapy
Time frame: Up to 4 months
Number of Participants Experiencing Treatment-Related Adverse Events During R-MACLO/IVAM Induction Therapy
Time frame: Up to 4 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 33735476Alderuccio 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Izidore S. Lossos, MD principal investigator
University of Miami
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing G-CSF, Rituximab and Cyclophosphamide in people with Mantle-Cell Lymphoma, run by University of Miami at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-Free Survival (PFS) (time frame: Up to 12 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00878254, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2025.