B-cell Childhood Acute Lymphoblastic LeukemiaPhase 2NCT00058461
Combination Chemotherapy and Rituximab in Treating Young Patients With Recurrent or Refractory Non-Hodgkin's Lymphoma or Acute Lymphoblastic Leukemia
A Phase 2 study testing ifosfamide, etoposide and rituximab in people with B-cell Childhood Acute Lymphoblastic Leukemia and Childhood Burkitt Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This phase II trial is studying how well rituximab together with ifosfamide, carboplatin, and etoposide works in treating young patients with recurrent or refractory non-Hodgkin's lymphoma or acute lymphoblastic leukemia. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- B-cell Childhood Acute Lymphoblastic Leukemia, Childhood Burkitt Lymphoma, Childhood Diffuse Large Cell Lymphoma
- What is being tested?
- ifosfamide, etoposide and rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 82 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2003to Mar 2007
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Histologically confirmed B-cell non-Hodgkin's lymphoma OR acute lymphoblastic leukemia
- CD20+ (confirmed by flow cytometry of tumor tissue, involved marrow, or CD20 immunostaining)
- The following histologies are generally CD20+ and are eligible:
- Diffuse large B-cell lymphoma, mediastinal (thymic) large B-cell lymphoma, or follicular lymphoma, grade III (rare), documented by flow cytometry or appropriate immunohistochemistry, any stage
- Burkitt's lymphoma or atypical Burkitt's/Burkitt-like lymphoma, any stage
- B-cell acute lymphoblastic leukemia, with FABL3 morphology and/or demonstration of surface immunoglobin by flow cytometry
Show all 43Show fewer
- Atypical precursor B-cell lymphoblastic lymphoma or other unusual histologies that are CD20+
- Measurable disease by clinical, radiographic, or histologic criteria
- Must be in first or later recurrence or have disease that is primarily refractory to conventional therapy
- No isolated CNS disease
- Performance status - ECOG 0-2
- At least 2 months
- Absolute neutrophil count ≥ 1,000/mm^3*
- Platelet count ≥ 100,000/mm^3 (transfusion independent)*
- Hemoglobin ≥ 10.0 g/dL (RBC transfusion allowed)*
- Bilirubin ≤ 1.5 times normal
- ALT < 2.5 times normal
- No chronic renal insufficiency
- Renal insufficiency allowed provided it is secondary to tumor lysis syndrome
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 3 months after study treatment
- HIV negative
- No active uncontrolled infection
- Seizure disorder allowed if well controlled with anticonvulsants
- No CNS toxicity greater than grade II
- At least 24 hours since prior growth factor(s)
- At least 60 days since prior biologic (antineoplastic) therapy
- Prior stem cell transplantation allowed provided the following criteria are met:
- More than 60 days since transplantation
- Hematopoietic lab value requirements are met (See Hematopoietic)
- No evidence of graft-versus-host disease (if post-allogeneic transplantation)
- Prior monoclonal antibody therapy allowed (including rituximab)
- No other concurrent immunomodulating agents
- More than 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas)
- No other concurrent chemotherapy
- No concurrent steroids (except for rituximab infusion-related symptoms)
- At least 2 weeks since prior local palliative radiotherapy (small port)
- At least 6 weeks since prior substantial bone marrow radiotherapy
- At least 6 months since prior craniospinal radiotherapy or radiotherapy to 50% or more of the pelvis
- Concurrent radiotherapy to localized painful, airway-compromising, or other acute organ-threatening lesions allowed provided at least 1 measurable lesion is not irradiated
- Recovered from prior therapy
- No concurrent participation in another phase II study
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Oncology Group
Arcadia, California, 91006-3776
About this study
Official title: A Phase II Study of Rituximab (IND #7028) and Ifosfamide, Carboplatin and Etoposide (ICE) Chemotherapy in Children With Recurrent/Refractory B-cell (CD20+) Non-Hodgkin Lymphoma and B-cell Acute Lymphoblastic Leukemia
This phase II trial is studying how well rituximab together with ifosfamide, carboplatin, and etoposide works in treating young patients with recurrent or refractory non-Hodgkin's lymphoma or acute lymphoblastic leukemia. Chemotherapy drugs, such as ifosfamide, carboplatin, and etoposide, work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining ifosfamide, carboplatin, and etoposide with rituximab may kill more cancer cells.
Read the detailed description
PRIMARY OBJECTIVES:
- Determine the response of pediatric patients with relapsed or refractory B-cell non-Hodgkin's lymphoma or acute lymphoblastic leukemia treated with ifosfamide, carboplatin, and etoposide combined with rituximab.
II. Determine the relapse-free survival rate of patients treated with this regimen.
III. Determine the toxicity profile of this regimen in these patients, specifically the frequency of therapy delays between courses due to prolonged grade IV hematologic toxicity.
SECONDARY OBJECTIVES:
- Determine whether this regimen plus filgrastim (G-CSF) will result in mobilization of greater than 2 X 10^6/kg peripheral blood stem cells (CD34+ cells, PBSC) in at least 80% of patients for whom peripheral stem cell collection is performed.
II. Determine the time course of engraftment for patients who undergo peripheral stem cell transplantation after collection of stem cells using this mobilization regimen.
OUTLINE: This is a multicenter study. Patients are stratified by disease (B-cell large cell lymphoma or atypical precursor B-cell lymphoblastic lymphoma vs small non-cleaved cell lymphoma or B-cell acute lymphoblastic leukemia).
Patients receive ifosfamide IV over 2 hours and etoposide IV over 1 hour on days 3-5, rituximab IV on days 1 and 3, and carboplatin IV over 1 hour on day 3. Patients receive filgrastim (G-CSF) subcutaneously once daily beginning on day 6 and continuing until blood counts recover. Patients also receive intrathecal (IT) chemotherapy comprising methotrexate and cytarabine. Patients with B-cell large cell lymphoma and negative CSF cytology receive IT chemotherapy on day 3 of the first course only. Patients with small non-cleaved cell lymphoma or B-cell acute lymphoblastic leukemia and negative CSF cytology receive IT chemotherapy on day 3. All patients with positive CSF cytology receive IT chemotherapy on days 3, 10, and 17 of the first and second courses. Treatment repeats every 23 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
Patients are followed for survival.
PROJECTED ACCRUAL: A total of 42-82 patients (21-41 per disease stratum) will be accrued for this study within 2-4 years.
- Conditions
- B-cell Childhood Acute Lymphoblastic Leukemia, Childhood Burkitt Lymphoma, Childhood Diffuse Large Cell Lymphoma, Childhood Immunoblastic Large Cell Lymphoma, L3 Childhood Acute Lymphoblastic Leukemia, Recurrent Childhood Acute Lymphoblastic Leukemia
- Being tested
- ifosfamide, etoposide, rituximab, carboplatin, filgrastim
- Medical subject headings
- Burkitt Lymphoma, Lymphoma, Large B-Cell, Diffuse, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Dendritic Cell Sarcoma, Interdigitating
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ifosfamideDrug
Given IV
etoposideDrug
Given IV
rituximabBiological
Given IV
carboplatinDrug
Given IV
filgrastimBiological
Given SC
methotrexateDrug
Given IT
cytarabineDrug
Given IT
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (chemotherapy, rituximab) | Experimental | Patients receive ifosfamide IV over 2 hours and etoposide IV over 1 hour on days 3-5, rituximab IV on days 1 and 3, and carboplatin IV over 1 hour on day 3. Patients receive filgrastim (G-CSF) subcutaneously once daily beginning on day 6 and continuing until blood counts recover. Patients also receive intrathecal (IT) chemotherapy comprising methotrexate and cytarabine. Patients with B-cell large cell lymphoma and negative CSF cytology receive IT chemotherapy on day 3 of the first course only. Patients with small non-cleaved cell lymphoma or B-cell acute lymphoblastic leukemia and negative CSF cytology receive IT chemotherapy on day 3. All patients with positive CSF cytology receive IT chemotherapy on days 3, 10, and 17 of the first and second courses. Treatment repeats every 23 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Receives: Drug: ifosfamide; Drug: etoposide; Biological: rituximab; Drug: carboplatin; Biological: filgrastim; Drug: methotrexate; Drug: cytarabine; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response rate determined by physical exam and appropriate imaging studies
Response rates and confidence intervals will be constructed according to the method of Chang and O'Brien.
Measured: Up to 3 years
Relapse-free survival rate
Estimated by the Kaplan-Meier method.
Measured: Up to 3 years
Toxicity as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)
Measured: Up to 3 years
Secondary outcomes (1)
CD34 cells mobilization by flow cytometry
Measured: At the completion of 2 courses of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2003 (estimated)
- Study startNov 2003
- Primary completionMar 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for B-cell Childhood Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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
- 82 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Timothy Griffin, Principal investigator, Children's Oncology Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00058461
- Sponsor's protocol ID
- NCI-2012-01804
- Other IDs
- NCI-2012-01804, COG-ANHL0121, CDR0000298751, ANHL0121, ANHL0121, U10CA098543
- Status last verified
- Oct 2013
- First submitted
- 7 Apr 2003
- Last updated
- 8 Oct 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Rituximab (IND #7028) and Ifosfamide, Carboplatin and Etoposide (ICE) Chemotherapy in Children With Recurrent/Refractory B-cell (CD20+) Non-Hodgkin Lymphoma and B-cell Acute Lymphoblastic Leukemia
- ClinicalTrials.gov ID
- NCT00058461
- Acronym / sponsor ID
- NCI-2012-01804
- Conditions
- B-cell Childhood Acute Lymphoblastic Leukemia, Childhood Burkitt Lymphoma, Childhood Diffuse Large Cell Lymphoma, Childhood Immunoblastic Large Cell Lymphoma, L3 Childhood Acute Lymphoblastic Leukemia, Recurrent Childhood Acute Lymphoblastic Leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 82 participants (estimated)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Nov 2003
- Primary completion
- Mar 2007 (actual)
- First posted
- 9 Apr 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial is studying how well rituximab together with ifosfamide, carboplatin, and etoposide works in treating young patients with recurrent or refractory non-Hodgkin's lymphoma or acute lymphoblastic leukemia. Chemotherapy drugs, such as ifosfamide, carboplatin, and etoposide, work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining ifosfamide, carboplatin, and etoposide with rituximab may kill more cancer cells.
Detailed description
PRIMARY OBJECTIVES:
- Determine the response of pediatric patients with relapsed or refractory B-cell non-Hodgkin's lymphoma or acute lymphoblastic leukemia treated with ifosfamide, carboplatin, and etoposide combined with rituximab.
II. Determine the relapse-free survival rate of patients treated with this regimen.
III. Determine the toxicity profile of this regimen in these patients, specifically the frequency of therapy delays between courses due to prolonged grade IV hematologic toxicity.
SECONDARY OBJECTIVES:
- Determine whether this regimen plus filgrastim (G-CSF) will result in mobilization of greater than 2 X 10^6/kg peripheral blood stem cells (CD34+ cells, PBSC) in at least 80% of patients for whom peripheral stem cell collection is performed.
II. Determine the time course of engraftment for patients who undergo peripheral stem cell transplantation after collection of stem cells using this mobilization regimen.
OUTLINE: This is a multicenter study. Patients are stratified by disease (B-cell large cell lymphoma or atypical precursor B-cell lymphoblastic lymphoma vs small non-cleaved cell lymphoma or B-cell acute lymphoblastic leukemia).
Patients receive ifosfamide IV over 2 hours and etoposide IV over 1 hour on days 3-5, rituximab IV on days 1 and 3, and carboplatin IV over 1 hour on day 3. Patients receive filgrastim (G-CSF) subcutaneously once daily beginning on day 6 and continuing until blood counts recover. Patients also receive intrathecal (IT) chemotherapy comprising methotrexate and cytarabine. Patients with B-cell large cell lymphoma and negative CSF cytology receive IT chemotherapy on day 3 of the first course only. Patients with small non-cleaved cell lymphoma or B-cell acute lymphoblastic leukemia and negative CSF cytology receive IT chemotherapy on day 3. All patients with positive CSF cytology receive IT chemotherapy on days 3, 10, and 17 of the first and second courses. Treatment repeats every 23 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
Patients are followed for survival.
PROJECTED ACCRUAL: A total of 42-82 patients (21-41 per disease stratum) will be accrued for this study within 2-4 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (chemotherapy, rituximab) | Experimental | Drug: ifosfamide, Drug: etoposide, Biological: rituximab, Drug: carboplatin, Biological: filgrastim, Drug: methotrexate, Drug: cytarabine, Other: laboratory biomarker analysisPatients receive ifosfamide IV over 2 hours and etoposide IV over 1 hour on days 3-5, rituximab IV on days 1 and 3, and carboplatin IV over 1 hour on day 3. Patients receive filgrastim (G-CSF) subcutaneously once daily beginning on day 6 and continuing until blood counts recover. Patients also receive intrathecal (IT) chemotherapy comprising methotrexate and cytarabine. Patients with B-cell large cell lymphoma and negative CSF cytology receive IT chemotherapy on day 3 of the first course only. Patients with small non-cleaved cell lymphoma or B-cell acute lymphoblastic leukemia and negative CSF cytology receive IT chemotherapy on day 3. All patients with positive CSF cytology receive IT chemotherapy on days 3, 10, and 17 of the first and second courses. Treatment repeats every 23 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (43 listed)
- Histologically confirmed B-cell non-Hodgkin's lymphoma OR acute lymphoblastic leukemia
- Measurable disease by clinical, radiographic, or histologic criteria
- Must be in first or later recurrence or have disease that is primarily refractory to conventional therapy
- No isolated CNS disease
- Performance status - ECOG 0-2
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| ifosfamideGiven IV | Drug | Treatment (chemotherapy, rituximab) |
| etoposideGiven IV | Drug | Treatment (chemotherapy, rituximab) |
| rituximabGiven IV | Biological | Treatment (chemotherapy, rituximab) |
| carboplatinGiven IV | Drug | Treatment (chemotherapy, rituximab) |
| filgrastimGiven SC | Biological | Treatment (chemotherapy, rituximab) |
| methotrexateGiven IT | Drug | Treatment (chemotherapy, rituximab) |
| cytarabineGiven IT | Drug | Treatment (chemotherapy, rituximab) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (chemotherapy, rituximab) |
Primary outcome
Response rate determined by physical exam and appropriate imaging studies
Time frame: Up to 3 years
Response rates and confidence intervals will be constructed according to the method of Chang and O'Brien.
Relapse-free survival rate
Time frame: Up to 3 years
Estimated by the Kaplan-Meier method.
Toxicity as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)
Time frame: Up to 3 years
1 secondary outcome
CD34 cells mobilization by flow cytometry
Time frame: At the completion of 2 courses of treatment
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2013.
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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.
Timothy Griffin principal investigator
Children's Oncology Group
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 ifosfamide, etoposide and rituximab in people with B-cell Childhood Acute Lymphoblastic Leukemia and Childhood Burkitt Lymphoma, run by National Cancer Institute (NCI) 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 43 inclusion and 0 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: stopped early, as of the sponsor's last update on 8 Oct 2013. 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?
The study was stopped early. Results are not available in the source record.
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?
Response rate determined by physical exam and appropriate imaging studies (time frame: Up to 3 years). The study lists 3 primary outcomes in all. 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 8 Oct 2013.