LeukemiaPhase 2NCT00133991
Combination Chemotherapy and Rituximab in Treating Patients With Newly Diagnosed Burkitt's Lymphoma or Leukemia
A Phase 2 study testing Filgrastim, Rituximab and Cyclophosphamide in people with Leukemia and Lymphoma, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 2 sites in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Read more about this study
- Who is it for?
- Ages 30 to 120 years
- What is being tested?
- Filgrastim, Rituximab and Cyclophosphamide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 2 sitesUnited States
- Study dates
- Jul 2005to Aug 2013
- 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 30 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically confirmed diagnosis of 1 of the following:
- Classic, sporadic Burkitt's lymphoma
- Burkitt's leukemia (FAB L3 acute lymphoblastic leukemia)
- Atypical Burkitt/Burkitt's-like lymphoma or leukemia, defined by the following criteria:
- Characteristic morphologic features
- High proliferative index AND Ki-67 ≥ 85%
- Any stage allowed
- Newly diagnosed or untreated disease
- Steroids allowed
PATIENT CHARACTERISTICS:
Age
- 30 and over
Performance status
- Not specified
Life expectancy
- Not specified
Renal
- No known irreversible renal dysfunction that would preclude treatment with high-dose cyclophosphamide
Cardiovascular
- No known significant cardiac dysfunction that would preclude treatment with high-dose cyclophosphamide
Other
- Not pregnant or nursing
- No known HIV positivity
- No other malignancy within the past 3 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- No prior chemotherapy for lymphoma
- A maximum of 2 prior doses of intrathecal chemotherapy are allowed
Endocrine therapy
- Not specified
Radiotherapy
- No prior radiation therapy for lymphoma
Surgery
- Prior complete or incomplete surgical resection of lymphoma allowed
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21231-2410
Drexel University College of Medicine - Center City Hahnemann Campus
Philadelphia, Pennsylvania, 19102
About this study
Official title: Phase II Study of Intensified CVP, Rituximab, and High Dose Cyclophosphamide for Adult Burkitt or Burkitt-Like Lymphoma
RATIONALE: Drugs used in chemotherapy, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving combination chemotherapy together with rituximab may kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with rituximab works in treating patients with newly diagnosed Burkitt's lymphoma or leukemia.
Read the detailed description
OBJECTIVES:
Primary
- Determine the overall response rate, 1-year event-free survival, and overall survival of adult patients with newly diagnosed Burkitt or atypical Burkitt lymphoma or leukemia treated with dose-intensified induction therapy comprising cyclophosphamide, vincristine, prednisone, and rituximab followed by consolidation therapy comprising rituximab and high-dose cyclophosphamide.
- Determine the grade 3 or higher non-hematologic toxic effects and overall tolerability of this regimen in these patients.
Secondary
- Determine the 3-year event-free survival and overall survival of patients treated with this regimen.
- Determine the general patterns of CNS and systemic relapse in patients treated with this regimen.
OUTLINE: This is a multicenter study.
- Dose-intensified CVP induction therapy: Patients receive cyclophosphamide IV and vincristine IV on day 1. Patients also receive oral prednisone on days 1-5 and rituximab IV on days 1 and 8, and high-dose methotrexate IV with leucovorin calcium IV rescue on day 8. Patients receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 3 and continuing until blood counts recover. Treatment repeats approximately every 14 days for 2 courses.
- CNS therapy: Patients receive cytarabine intrathecally (IT) with or without hydrocortisone IT on days 1, 4, and 11 of each induction therapy course. Patients with evidence of CNS involvement by lymphoma continue to receive cytarabine IT twice weekly during any induction therapy treatment delay. Patients who demonstrate CSF clearance receive cytarabine IT once weekly for 4 doses and then once every other week for 4 doses during consolidation therapy. Patients with disease progression during induction therapy or persistent CNS involvement by lymphoma are removed from the study. All other patients proceed to consolidation therapy.
- Consolidation therapy: Patients receive rituximab IV on day -4 and high-dose cyclophosphamide IV on days -3, -2, -1, and 0. Patients receive G-CSF SC once daily beginning on day 6 and continuing until blood counts recover OR pegfilgrastim SC once on day 6. Patients then receive rituximab IV once weekly for 4 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed periodically for 3 years.
PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 3 years.
- Being tested
- Filgrastim, Rituximab, Cyclophosphamide, Cytarabine, Methotrexate
- Keywords
- untreated adult acute lymphoblastic leukemia, L3 adult acute lymphoblastic leukemia, contiguous stage II adult Burkitt lymphoma, noncontiguous stage II adult Burkitt lymphoma, stage I adult Burkitt lymphoma, stage III adult Burkitt lymphoma, stage IV adult Burkitt lymphoma
- Medical subject headings
- Leukemia, Lymphoma, Burkitt Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FilgrastimBiological
Also called Neupogen, G-CSF
5 mcg/kg/day starting on Day 3 after each R-CVP cycle and on Day 6 after HiCy.
RituximabBiological
Also called Rituxan
375 mg/m^2 on Day 1 and Day 8 of each R-CVP cycle. 375 mg/m^2 on Day -4 of HiCy and weekly for four weeks after HiCy.
CyclophosphamideDrug
Also called Cytoxan, Cy, CTX, HiCy
1500 mg/m^2 on Day 1 of each R-CVP cycle. 50 mg/kg/day on Days -3, -2, -1, and 0 of HiCy.
CytarabineDrug
Also called Ara-C
100 mg intrathecal on Days 1, 4, and 11 of each cycle of R-CVP.
MethotrexateDrug
Also called MTX
3 g/m^2 on Day 8 of each cycle of R-CVP.
PrednisoneDrug
Also called Deltasone
100 mg on Days 1-5 of each cycle of R-CVP.
HydrocortisoneDrug
50 mg intrathecal on Days 1, 4, and 11 of each cycle of R-CVP.
VincristineDrug
Also called Oncovin
1.4 mg/m^2 on Day 1 of each cycle of R-CVP.
LeucovorinDrug
Also called Folinic acid
25 mg four times daily after methotrexate administration. Dosing continues until adequate methotrexate levels are reached.
| Study group | Role | What they receive |
|---|---|---|
| R-CVP + HiCy | Experimental | Protocol intervention consists of two fifteen-day cycles of cyclophosphamide (Cy), vincristine (V), prednisone (P), rituximab (R), with filgrastim support. CNS intervention consists of three days of cytarabine and hydrocortisone and one day of methotrexate (with leucovorin support) for each cycle. After those two cycles, rituximab and high-dose cyclophosphamide (HiCy) will be given. Receives: Biological: Filgrastim; Biological: Rituximab; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Methotrexate; Drug: Prednisone; Drug: Hydrocortisone; Drug: Vincristine; Drug: Leucovorin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate
Number of participants who have a complete or partial remission (2007 International Working Group criteria).
Measured: Up to 3 months
Overall Survival
Percentage of participants alive at 1 year and at 3 years.
Measured: 1 year and 3 years
Event-free Survival
Percentage of participants alive without relapse at 1 year and 3 years.
Measured: 1 year and 3 years
Percentage of Participants Experiencing Grade 3-5 Toxicity
Percentage of participants experiencing at least one grade 3-5 adverse event (by CTCAE 3.0 criteria).
Measured: Up to 2 years
Secondary outcomes (1)
Relapse Pattern
Percentage of participants experiencing central nervous system (CNS) and systemic relapse.
Measured: Up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2005 (estimated)
- Study startJul 2005
- Primary completionAug 2011
- Study completionAug 2013
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 LeukemiaStudies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe 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
- 23 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Yvette L. Kasamon, MD, Study chair, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00133991
- Sponsor's protocol ID
- J0409
- Other IDs
- P50CA096888, P30CA006973, NA_00035765
- Status last verified
- Sep 2018
- First submitted
- 22 Aug 2005
- Last updated
- 17 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Individual data sharing
- No
Publications
Kasamon YL, Brodsky RA, Borowitz MJ, Ambinder RF, Crilley PA, Cho SY, Tsai HL, Smith BD, Gladstone DE, Carraway HE, Huff CA, Matsui WH, Bolanos-Meade J, Jones RJ, Swinnen LJ. Brief intensive therapy for older adults with newly diagnosed Burkitt or atypical Burkitt lymphoma/leukemia. Leuk Lymphoma. 2013 Mar;54(3):483-90. doi: 10.3109/10428194.2012.715346. Epub 2012 Aug 17.
PubMed 22835045
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Intensified CVP, Rituximab, and High Dose Cyclophosphamide for Adult Burkitt or Burkitt-Like Lymphoma
- ClinicalTrials.gov ID
- NCT00133991
- Acronym / sponsor ID
- J0409
- Keywords
- untreated adult acute lymphoblastic leukemia, L3 adult acute lymphoblastic leukemia, contiguous stage II adult Burkitt lymphoma, noncontiguous stage II adult Burkitt lymphoma, stage I adult Burkitt lymphoma, stage III adult Burkitt lymphoma, stage IV adult Burkitt lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jul 2005 (actual)
- Primary completion
- Aug 2011 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 24 Aug 2005 (estimated)
- Results
- Posted 17 Sep 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Drugs used in chemotherapy, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving combination chemotherapy together with rituximab may kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with rituximab works in treating patients with newly diagnosed Burkitt's lymphoma or leukemia.
Detailed description
OBJECTIVES:
Primary
- Determine the overall response rate, 1-year event-free survival, and overall survival of adult patients with newly diagnosed Burkitt or atypical Burkitt lymphoma or leukemia treated with dose-intensified induction therapy comprising cyclophosphamide, vincristine, prednisone, and rituximab followed by consolidation therapy comprising rituximab and high-dose cyclophosphamide.
- Determine the grade 3 or higher non-hematologic toxic effects and overall tolerability of this regimen in these patients.
Secondary
- Determine the 3-year event-free survival and overall survival of patients treated with this regimen.
- Determine the general patterns of CNS and systemic relapse in patients treated with this regimen.
OUTLINE: This is a multicenter study.
- Dose-intensified CVP induction therapy: Patients receive cyclophosphamide IV and vincristine IV on day 1. Patients also receive oral prednisone on days 1-5 and rituximab IV on days 1 and 8, and high-dose methotrexate IV with leucovorin calcium IV rescue on day 8. Patients receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 3 and continuing until blood counts recover. Treatment repeats approximately every 14 days for 2 courses.
- CNS therapy: Patients receive cytarabine intrathecally (IT) with or without hydrocortisone IT on days 1, 4, and 11 of each induction therapy course. Patients with evidence of CNS involvement by lymphoma continue to receive cytarabine IT twice weekly during any induction therapy treatment delay. Patients who demonstrate CSF clearance receive cytarabine IT once weekly for 4 doses and then once every other week for 4 doses during consolidation therapy. Patients with disease progression during induction therapy or persistent CNS involvement by lymphoma are removed from the study. All other patients proceed to consolidation therapy.
- Consolidation therapy: Patients receive rituximab IV on day -4 and high-dose cyclophosphamide IV on days -3, -2, -1, and 0. Patients receive G-CSF SC once daily beginning on day 6 and continuing until blood counts recover OR pegfilgrastim SC once on day 6. Patients then receive rituximab IV once weekly for 4 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed periodically for 3 years.
PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 3 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| R-CVP + HiCy | Experimental | Biological: Filgrastim, Biological: Rituximab, Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Methotrexate, Drug: Prednisone, Drug: Hydrocortisone, Drug: Vincristine, Drug: LeucovorinProtocol intervention consists of two fifteen-day cycles of cyclophosphamide (Cy), vincristine (V), prednisone (P), rituximab (R), with filgrastim support. CNS intervention consists of three days of cytarabine and hydrocortisone and one day of methotrexate (with leucovorin support) for each cycle. After those two cycles, rituximab and high-dose cyclophosphamide (HiCy) will be given. |
Who may qualify
- Ages
- 30 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| FilgrastimAlso: Neupogen, G-CSF5 mcg/kg/day starting on Day 3 after each R-CVP cycle and on Day 6 after HiCy. | Biological | R-CVP + HiCy |
| RituximabAlso: Rituxan375 mg/m^2 on Day 1 and Day 8 of each R-CVP cycle. 375 mg/m^2 on Day -4 of HiCy and weekly for four weeks after HiCy. | Biological | R-CVP + HiCy |
| CyclophosphamideAlso: Cytoxan, Cy, CTX, HiCy1500 mg/m^2 on Day 1 of each R-CVP cycle. 50 mg/kg/day on Days -3, -2, -1, and 0 of HiCy. | Drug | R-CVP + HiCy |
| CytarabineAlso: Ara-C100 mg intrathecal on Days 1, 4, and 11 of each cycle of R-CVP. | Drug | R-CVP + HiCy |
| MethotrexateAlso: MTX3 g/m^2 on Day 8 of each cycle of R-CVP. | Drug | R-CVP + HiCy |
| PrednisoneAlso: Deltasone100 mg on Days 1-5 of each cycle of R-CVP. | Drug | R-CVP + HiCy |
| Hydrocortisone50 mg intrathecal on Days 1, 4, and 11 of each cycle of R-CVP. | Drug | R-CVP + HiCy |
| VincristineAlso: Oncovin1.4 mg/m^2 on Day 1 of each cycle of R-CVP. | Drug | R-CVP + HiCy |
| LeucovorinAlso: Folinic acid25 mg four times daily after methotrexate administration. Dosing continues until adequate methotrexate levels are reached. | Drug | R-CVP + HiCy |
Primary outcome
Overall Response Rate
Time frame: Up to 3 months
Number of participants who have a complete or partial remission (2007 International Working Group criteria).
Overall Survival
Time frame: 1 year and 3 years
Percentage of participants alive at 1 year and at 3 years.
Event-free Survival
Time frame: 1 year and 3 years
Percentage of participants alive without relapse at 1 year and 3 years.
Percentage of Participants Experiencing Grade 3-5 Toxicity
Time frame: Up to 2 years
Percentage of participants experiencing at least one grade 3-5 adverse event (by CTCAE 3.0 criteria).
1 secondary outcome
Relapse Pattern
Time frame: Up to 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22835045Kasamon YL, Brodsky RA, Borowitz MJ, Ambinder RF, Crilley PA, Cho SY, Tsai HL, Smith BD, Gladstone DE, Carraway HE, Huff CA, Matsui WH, Bolanos-Meade J, Jones RJ, Swinnen LJ. Brief intensive therapy for older adults with newly diagnosed Burkitt or atypical Burkitt lymphoma/leukemia. Leuk Lymphoma. 2013 Mar;54(3):483-90. doi: 10.3109/10428194.2012.715346. Epub 2012 Aug 17.
- 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.
Yvette L. Kasamon, MD study chair
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Filgrastim, Rituximab and Cyclophosphamide in people with Leukemia and Lymphoma, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 2 sites 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?
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 17 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 17 Sep 2018). 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?
Overall Response Rate (time frame: Up to 3 months). The study lists 4 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 NCT00133991, 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 17 Sep 2018.