LymphomaPhase 2NCT00588094
Dose Augmented Rituximab and ICE for Pts With Primary Refractory and Poor Risk Relapsed Aggressive B-Cell NHL
A Phase 2 study testing Rituximab, Ifosfamide, Carboplatin, VP-16, Mesna, G-CSF, Stem Cell Transplant in people with Lymphoma and B-cell Non-Hodgkin's Lymphoma, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial summary
The purpose of this research is to study a treatment program for patients with aggressive lymphoma that has come back after initial or first therapy (called relapsed) or that has not responded to first therapy (called refractory). Read more about this study
- Who is it for?
- Ages 18 to 72 years
- Conditions the study is for
- Lymphoma, B-cell Non-Hodgkin's Lymphoma
- What is being tested?
- Rituximab, Ifosfamide, Carboplatin, VP-16, Mesna, G-CSF, Stem Cell Transplant
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2003to Mar 2010
- 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 to 72 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologic diagnosis of the one of the following B cell aggressive lymphomas, confirmed by an MSKCC pathologist: Diffuse Large, Immunoblastic, Mantle cell, Anaplastic Large Cell, De novo transformation of follicular lymphoma, or classical Hodgkin's lymphoma which is CD20 antigen positive.
- Tumors must stain positive for CD20.
- Primary refractory disease proven by biopsy or fine needle aspiration (cytology) of an involved site
- Relapsed diffuse large, immunoblastic, anaplastic, de novo transformation of follicular lymphoma, or classical Hodgkin's lymphoma which is CD20 antigen positive proven by biopsy or fine needle aspiration (cytology) of an involved field site and at least two of the three following risk factors: LDH> upper limit of normal, KPS < 80%, Stage III or IV disease.
- All mantle cell lymphoma patients in first relapse
- Failure of doxorubicin or mitoxantrone containing front-line therapy
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- Bidimensionally measurable disease.
- Cardiac ejection fraction of greater than 50%, measured since last chemotherapy.
- Serum creatinine <1.5 mg/dl; if creatinine >1.5 mg/dl then the measured 12- or 24-hour creatinine clearance must be >60 ml/minute.
- ANC>1000/µl and Platelets>50,000/µl
- Total bilirubin < 2.0 mg/dl in the absence of a history of Gilbert's disease.
- Females of childbearing age must be on an acceptable form of birth control.
- Age between 18 and 72
- HIV I and II negative.
- Patients or their guardians must be capable of providing informed consent.
Who cannot join
- Any lymphoma subtype other than those described among the inclusion criteria.
- All patients with relapsed diffuse large, immunoblastic, anaplastic, de novo transformation of follicular lymphoma, or classical Hodgkin's lymphoma which is CD20 antigen positive disease who have <2 of following risk factors: LDH> upper limit of normal, KPS < 80%, Stage III or IV disease.
- History of second-line chemotherapy
- Presence of CNS involvement.
- Prior treatment with carboplatin, cisplatin, ifosfamide, or etoposide
- Hepatitis B surface antigen positive.
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- Known pregnancy or breast-feeding.
- Medical illness unrelated to NHL, which in the opinion of the attending physician and/or principal investigator will preclude administering chemotherapy safely.
- History of any malignancy for which the disease-free interval is <5 years, excluding curatively treated cutaneous basal cell or squamous cell carcinoma and carcinoma in-situ of the cervix
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
About this study
Official title: A Phase II Study of Dose Augmented Rituximab and Ice for Patients With Primary Refractory and Poor Risk Relapsed Aggressive B-Cell Non-Hodgkin's Lymphoma Undergoing Second-Line Therapy Prior to Stem Cell Transplantation
The purpose of this research is to study a treatment program for patients with aggressive lymphoma that has come back after initial or first therapy (called relapsed) or that has not responded to first therapy (called refractory). Since 1993, we have used a combination of chemotherapy known as ICE (Ifosfamide, Carboplatin, and Etoposide) for your type of lymphoma. In many patients, this treatment helps the disease to shrink before giving high-dose therapy and autologous stem cell transplant (ASCT). Only patients who respond to these types of treatments have a chance of their disease going away (remission) with an ASCT. In 1999, we studied the same treatment but added another medicine for your type of lymphoma, Rituximab (Rituxan), to the ICE treatment (RICE). More patients had lymphoma shrinkage from this treatment (chemosensitive disease) than with ICE alone. These patients then received high dose therapy and autologous stem cell transplant and have an improved chance of having a remission.
ICE chemotherapy is standard chemotherapy used at Memorial Sloan-Kettering Cancer Center. However, it is different in this study because of the higher doses. We are testing higher doses of RICE treatment for patients in this study.
In our current study in Hodgkin's lymphoma, we are giving these higher doses of ICE (called augmented ICE) to patients who also have higher risk. We hope to show in this study that by using Rituximab and augmented ICE that we can improve your ability to achieve a remission (that is, to have the disease go away).
Read the detailed description
The purpose of this study is to determine if dose escalation of the rituximab-ICE (RICEesc) program can improve the overall response rate of patients with primary refractory or poor risk relapsed aggressive B cell lymphoma. R-ICEesc will be administered for 2 cycles with peripheral blood progenitor cells (PBPCs) collected after cycle 2.
A two-stage design will be employed, such that the study will be terminated if in the first cohort of patients it appears that the overall response rate is <50% or if >25% patients fail to mobilize at least 2 x 106 CD34+ cells/kg.
- Conditions
- Lymphoma, B-cell Non-Hodgkin's Lymphoma
- Being tested
- Rituximab, Ifosfamide, Carboplatin, VP-16, Mesna, G-CSF, Stem Cell Transplant
- Keywords
- Lymphoma, ASCT, B-cell non-Hodgkin's lymphoma, Cancer, Second line therapy, ICE, Stem cell transplant
- Medical subject headings
- Lymphoma, Lymphoma, B-Cell, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rituximab, Ifosfamide, Carboplatin, VP-16, Mesna, G-CSF, Stem Cell TransplantDrug
Also called ASCT,Rituxan, Ifex, Paraplatin®, etoposide, Vepesid®, Mesnex®, Neupogen, Neulasta
ANC must be ≥1000/µl and platelet count must be ≥50,000/µl. Rituximab will be administered at a dose of 375 mg/m2 IV on days 1 and 3 of the each cycle. Premedication will be given.ICE will be administered as follows: Day 3: Etoposide 200 mg/m2 IV q12 hrs x 3. Day 4: Ifosfamide 10 g/m2 and MESNA 10 g/m2 mixed and infused together as a continuous infusion over 48 hours. Day 5: Carboplatin IV dosed by the Calvert formula using an AUC of 5.
Carboplatin dose (mg) = 5 x (Clcr + 25) For the first ten patients enrolled, G CSF will be administered beginning on day seven of each cycle and G CSF will continue until stem cell collection is completed. The dose will be 960 ug or 10 ug/kg if weight is greater than 100 kg.
For the remaining patients, G-CSF will be administered for 10 days beginning on day 7 for cycle 1. The dose will be 300-480 ug/d. For cycle 2 the dose will be 960 ug or 10ug/kg if weight is > 100kg. Leukapheresis will continue.
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | R-ICEesc will be administered with the intent of administering 2 cycles, each 21 days apart admixed with 4 doses of rituximab. G-CSF will be administered at 960 ug or 10 ug/kg if patient is > 100 kg after cycles one and two for PBPC collection for the first 10 patients enrolled. G-CSF will be administered in standard dosing for cycle one and then at 960 ug or 10 ug/kg (if patient is > 100 kg) after cycle two for PBPC collection for the remaining 22 patients. All responding patients who make at least 2 x 106 CD34+ cells/kg will receive high dose therapy and ASCT on other protocols. Receives: Drug: Rituximab, Ifosfamide, Carboplatin, VP-16, Mesna, G-CSF, Stem Cell Transplant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improve the Overall Response Rate
assessing the response rate (CR+PR)
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2008 (estimated)
- Study startOct 2003
- Primary completionMar 2010
- Study completionMar 2010
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.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe 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
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Craig Moskowitz, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00588094
- Sponsor's protocol ID
- 03-075
- Status last verified
- Oct 2015
- First submitted
- 26 Dec 2007
- Last updated
- 4 Dec 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Dose Augmented Rituximab and Ice for Patients With Primary Refractory and Poor Risk Relapsed Aggressive B-Cell Non-Hodgkin's Lymphoma Undergoing Second-Line Therapy Prior to Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT00588094
- Acronym / sponsor ID
- 03-075
- Conditions
- Lymphoma, B-cell Non-Hodgkin's Lymphoma
- Keywords
- Lymphoma, ASCT, B-cell non-Hodgkin's lymphoma, Cancer, Second line therapy, ICE, Stem cell transplant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Study start
- Oct 2003
- Primary completion
- Mar 2010 (actual)
- Study completion
- Mar 2010 (actual)
- First posted
- 8 Jan 2008 (estimated)
- Results
- Posted 4 Dec 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research is to study a treatment program for patients with aggressive lymphoma that has come back after initial or first therapy (called relapsed) or that has not responded to first therapy (called refractory). Since 1993, we have used a combination of chemotherapy known as ICE (Ifosfamide, Carboplatin, and Etoposide) for your type of lymphoma. In many patients, this treatment helps the disease to shrink before giving high-dose therapy and autologous stem cell transplant (ASCT). Only patients who respond to these types of treatments have a chance of their disease going away (remission) with an ASCT. In 1999, we studied the same treatment but added another medicine for your type of lymphoma, Rituximab (Rituxan), to the ICE treatment (RICE). More patients had lymphoma shrinkage from this treatment (chemosensitive disease) than with ICE alone. These patients then received high dose therapy and autologous stem cell transplant and have an improved chance of having a remission.
ICE chemotherapy is standard chemotherapy used at Memorial Sloan-Kettering Cancer Center. However, it is different in this study because of the higher doses. We are testing higher doses of RICE treatment for patients in this study.
In our current study in Hodgkin's lymphoma, we are giving these higher doses of ICE (called augmented ICE) to patients who also have higher risk. We hope to show in this study that by using Rituximab and augmented ICE that we can improve your ability to achieve a remission (that is, to have the disease go away).
Detailed description
The purpose of this study is to determine if dose escalation of the rituximab-ICE (RICEesc) program can improve the overall response rate of patients with primary refractory or poor risk relapsed aggressive B cell lymphoma. R-ICEesc will be administered for 2 cycles with peripheral blood progenitor cells (PBPCs) collected after cycle 2.
A two-stage design will be employed, such that the study will be terminated if in the first cohort of patients it appears that the overall response rate is <50% or if >25% patients fail to mobilize at least 2 x 106 CD34+ cells/kg.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: Rituximab, Ifosfamide, Carboplatin, VP-16, Mesna, G-CSF, Stem Cell TransplantR-ICEesc will be administered with the intent of administering 2 cycles, each 21 days apart admixed with 4 doses of rituximab. G-CSF will be administered at 960 ug or 10 ug/kg if patient is > 100 kg after cycles one and two for PBPC collection for the first 10 patients enrolled. G-CSF will be administered in standard dosing for cycle one and then at 960 ug or 10 ug/kg (if patient is > 100 kg) after cycle two for PBPC collection for the remaining 22 patients. All responding patients who make at least 2 x 106 CD34+ cells/kg will receive high dose therapy and ASCT on other protocols. |
Who may qualify
- Ages
- 18 to 72 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Histologic diagnosis of the one of the following B cell aggressive lymphomas, confirmed by an MSKCC pathologist: Diffuse Large, Immunoblastic, Mantle cell, Anaplastic Large Cell, De novo transformation of follicular lymphoma, or classical Hodgkin's lymphoma which is CD20 antigen positive.
- Tumors must stain positive for CD20.
- Primary refractory disease proven by biopsy or fine needle aspiration (cytology) of an involved site
- Relapsed diffuse large, immunoblastic, anaplastic, de novo transformation of follicular lymphoma, or classical Hodgkin's lymphoma which is CD20 antigen positive proven by biopsy or fine needle aspiration (cytology) of an involved field site and at least two of the three following risk factors: LDH> upper limit of normal, KPS < 80%, Stage III or IV disease.
- All mantle cell lymphoma patients in first relapse
Key exclusion criteria (9 listed)
- Any lymphoma subtype other than those described among the inclusion criteria.
- All patients with relapsed diffuse large, immunoblastic, anaplastic, de novo transformation of follicular lymphoma, or classical Hodgkin's lymphoma which is CD20 antigen positive disease who have <2 of following risk factors: LDH> upper limit of normal, KPS < 80%, Stage III or IV disease.
- History of second-line chemotherapy
- Presence of CNS involvement.
- Prior treatment with carboplatin, cisplatin, ifosfamide, or etoposide
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 |
|---|---|---|
| Rituximab, Ifosfamide, Carboplatin, VP-16, Mesna, G-CSF, Stem Cell TransplantAlso: ASCT,Rituxan, Ifex, Paraplatin®, etoposide, Vepesid®, Mesnex®, Neupogen, NeulastaANC must be ≥1000/µl and platelet count must be ≥50,000/µl. Rituximab will be administered at a dose of 375 mg/m2 IV on days 1 and 3 of the each cycle. Premedication will be given.ICE will be administered as follows: Day 3: Etoposide 200 mg/m2 IV q12 hrs x 3. Day 4: Ifosfamide 10 g/m2 and MESNA 10 g/m2 mixed and infused together as a continuous infusion over 48 hours. Day 5: Carboplatin IV dosed by the Calvert formula using an AUC of 5. Carboplatin dose (mg) = 5 x (Clcr + 25) For the first ten patients enrolled, G CSF will be administered beginning on day seven of each cycle and G CSF will continue until stem cell collection is completed. The dose will be 960 ug or 10 ug/kg if weight is greater than 100 kg. For the remaining patients, G-CSF will be administered for 10 days beginning on day 7 for cycle 1. The dose will be 300-480 ug/d. For cycle 2 the dose will be 960 ug or 10ug/kg if weight is > 100kg. Leukapheresis will continue. | Drug | Treatment |
Primary outcome
Improve the Overall Response Rate
Time frame: 2 years
assessing the response rate (CR+PR)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Memorial Sloan-Kettering web siteLink provided by the sponsor.
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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.
Craig Moskowitz, MD principal investigator
Memorial Sloan Kettering Cancer Center
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 Rituximab, Ifosfamide, Carboplatin, VP-16, Mesna, G-CSF, Stem Cell Transplant in people with Lymphoma and B-cell Non-Hodgkin's Lymphoma, run by Memorial Sloan Kettering Cancer Center 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 15 inclusion and 9 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 4 Dec 2015. 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 4 Dec 2015). 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?
Improve the Overall Response Rate (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Dec 2015.