LeukemiaRituximabNCT01230788
Rituximab for Patients With Relapsed Acute Lymphoblastic Leukemia
A study testing rituximab in people with Leukemia and Acute Lymphoblastic Leukemia, run by Emory University at 3 sites in United States.
Trial summary
This is a pilot study of a drug called rituximab used together with other drugs-prednisone, etoposide, and ifosfamide. Prednisone, etoposide, and ifosfamide have been used as part of standard chemotherapy for relapsed Acute Lymphoblastic Leukemia (ALL). Read more about this study
- Who is it for?
- Ages 1 year to 30 years
- Conditions the study is for
- Leukemia, Acute Lymphoblastic Leukemia, ALL
- What is being tested?
- rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 3 sitesUnited States
- Study dates
- Sep 2010to Oct 2012
- Phase
- Interventional
- 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 1 year to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age: Patients must be 1-30 years of age at initial diagnosis.
- Diagnosis: Patients must have histologically-confirmed relapsed/refractory Acute Lymphoblastic Leukemia (ALL).
- Disease Status:Patients must be in
- second or greater bone marrow relapse (≥ 25% blasts by morphology), or
- refractory to reinduction therapy with one or more attempts at remission reinduction (end of reinduction blasts ≥ 5% by morphology and/or end of reinduction MRD ≥ 1% by flow cytometry).
- Patients with combined bone marrow and extramedullary relapse are eligible (CNS 3 patients excluded).
Show all 21Show fewer
- Performance Status: Patients must have a performance status of ≥50 from the Lansky Scale if <10 years or ≥ 50 or from the Karnofsky Scale if ≥ 10 years. Patients who are unable to walk because of paralysis, but who are up in a wheelchair will be considered ambulatory for the purpose of assessing the performance score.
- Prior Therapy: Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study and meet time restrictions from end of prior therapy as stated below:
- Myelosuppressive chemotherapy: must not have received within 2 weeks of entry onto this study (4 weeks in the case of nitrosurea containing therapy). Patients who relapse while receiving ALL maintenance chemotherapy will not be required to have a waiting period before entry onto this study. Cytoreduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start of therapy.
- XRT: must be ≥ 4 weeks since the completion of radiation therapy.
- Study specific limitations: must be ≥ 7 days since the completion of corticosteroid therapy.
- Growth factor(s): Must not have received any hematopoietic growth factors (GCSF, Neulasta, or GMCSF) within 7 days of study entry.
- Stem Cell Transplant: Patients must be at least two months from stem cell transplant, must be off immunosuppressives, and must have no evidence of active graft versus host disease.
- Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair.
- Institutional review board approval.
- Individual informed consent per local guidelines and federal and state regulations.
- Organ Function: All patients must have adequate organ function defined as:
- Renal Function: Patients must have a calculated creatinine clearance or radioisotope GFR ≥ 70mL/min/1.73m2 or a normal serum creatinine based on age/gender.
- Liver Function: Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) for age, AND SGPT (ALT) ≤ 5 x institutional ULN for age
- Cardiac Function: Ejection fraction > 50% on echocardiogram or MUGA Scan, OR Shortening fraction ≥ 27% on echocardiogram or MUGA Scan
- Reproductive Function: Due to potential teratogenic effects of the drugs, all post-menarchal female patients must have a negative serum beta HCG prior to study enrollment. In addition, all patients of childbearing or child-fathering potential must agree to a medically acceptable form of contraception, including abstinence, while on study.
Who cannot join
- Patients with an active and uncontrolled infection, defined as need for pressors, and/or positive cultures for 24 hours.
- Patients recovering from allogeneic bone marrow transplantation who are still on immunosupressants.
- Pregnant or lactating females. Women of childbearing age will agree to use contraception during the protocol.
- Patients currently receiving other investigational agents, medications, or supplements with a known anti-leukemic effect.
- Patients who, in the opinion of the investigator, will not be able to comply with safety monitoring requirements of the study.
- Patients with reactivation of hepatitis B prior to starting therapy.
- Patients who are HIV positive.
- Patients must not have CNS 3 involvement.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Children's Healthcare of Atlanta
Atlanta, Georgia, 30322
Emory University
Atlanta, Georgia, 30322
The children's Mercy Hospital
Kansas City, Missouri, 64108
About this study
Official title: A Trial of Rituximab Combined With Prednisone/Ifosfamide/Etoposide for Relapsed Acute Lymphoblastic Leukemia (ALL)
This is a pilot study of a drug called rituximab used together with other drugs-prednisone, etoposide, and ifosfamide. Prednisone, etoposide, and ifosfamide have been used as part of standard chemotherapy for relapsed Acute Lymphoblastic Leukemia (ALL). Rituximab was approved by the Food and Drug Administration in 1997. However, the use of rituximab with prednisone, etoposide, and ifosfamide in pediatric patients with relapsed or refractory ALL is considered experimental.
This study is for patients who have ALL in second or greater relapse, or in first relapse and not responding to treatment.
Read more
The goals of this study are:
- To see if using rituximab with prednisone, etoposide, and ifosfamide is beneficial to leukemia treatment
- To find out what side effects this combination of drugs can cause
A total of 15 participants (30 years old or younger) will be enrolled, over a period of 2 years.
Read the detailed description
Rationale for study design:
The combination of etoposide and ifosfamide is a reinduction regimen used in many previous studies for pediatric B lineage acute lymphoblastic leukemia (ALL). It does not use anthracyclines, and therefore can be safely used in patients at risk for cardiac toxicity due to previous anthracycline use.
Previous studies in adult patients with ALL have demonstrated safety and efficacy with the addition of rituximab to other induction regimens. Rituximab is an anti-CD20 monoclonal antibody. Approximately one-half of pediatric cases of B precursor ALL express the CD20 antigen on the leukemic blasts. The use of rituximab provides a potential target for CD20 positive cells, therefore improving the rates of cytotoxicity associated with the chemotherapy. Rituximab has been previously utilized in many pediatric and adult regimens in combination with other chemotherapeutic agents, and is expected to be safe with the combination of etoposide and ifosfamide. However, since it has never been studied with this combination of chemotherapy, strict stopping rules are in place to ensure that it is a safe combination.
A recent study demonstrated upregulation of CD20 expression on leukemic blasts exposed to one week of prednisone therapy. This increase in expression occurred in the majority of B-ALL patient samples, regardless of whether the patient initially expressed CD20 on the surface of the leukemic blasts. In those samples with upregulation of CD20 treated with rituximab, cytotoxicity from rituximab was more successful than in samples with a smaller percentage of CD20 expression.
Therefore, prednisone will be given for two weeks in combination with etoposide and ifosfamide. It is hoped that the percentage of leukemic blasts expressing CD20 will increase with this combination of medications, allowing the rituximab to be more effective when given weekly starting on day 8 of therapy. To better understand this process, samples of blood and bone marrow will be collected to quantify CD20 expression and the amount of leukemia present at multiple time points during the month of study duration.
- Conditions
- Leukemia, Acute Lymphoblastic Leukemia, ALL
- Being tested
- rituximab
- Keywords
- ALL, Leukemia, Rituximab, Pediatrics
- Medical subject headings
- Leukemia, Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rituximabDrug
375 mg/m2/dose on days 8, 15, 22, and 29 (diluted in NS to a final concentration of 1 mg/ml for ease of administration). (Premedicate with Acetaminophen 15 mg/kg po (max 650 mg) and Diphenhydramine 1 mg/kg IV/PO (max 50 mg)).
| Study group | Role | What they receive |
|---|---|---|
| rituximab | Experimental | study drug given Receives: Drug: rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
4 Month Event Free Survival (EFS)
To estimate the 4 month EFS after therapy with rituximab and cytotoxic chemotherapy (prednisone/etoposide/ifosfamide) in patients with second relapse/refractory ALL.
Measured: one year after enrollment
Toxicities of Rituximab
To describe the toxicities of rituximab in addition to prednisone, etoposide, and ifosfamide.
Measured: two months after treatment
Remission Induction Rate
To estimate the remission induction rate of the addition of rituximab to cytotoxic chemotherapy (prednisone/etoposide/ifosfamide) in patients with second relapse/refractory ALL.
Measured: one month
Secondary outcomes (2)
Minimal Residual Disease
To perform serial minimal residual disease (MRD) measurements to provide an objective determination of the effectiveness of this therapy.
Measured: one month after treatment
Prednisone Effect
To correlate the effect of prednisone on CD20 expression using serial measurements of CD20 expression in leukemic blasts.
Measured: one month after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2010 (estimated)
- Study startSep 2010
- Primary completionOct 2012
- Study completionOct 2012
Why it stopped: Lack of enrollment
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 LeukemiaStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Todd M. Cooper, Emory University
- Investigators
- Todd Cooper, DO, Principal investigator, Emory University/Children's Healthcare of Atlanta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01230788
- Sponsor's protocol ID
- IRB00039682
- Other IDs
- Rituximab
- Acronym
- Rituximab
- Status last verified
- Nov 2014
- First submitted
- 23 Oct 2010
- Last updated
- 1 Dec 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 1 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Trial of Rituximab Combined With Prednisone/Ifosfamide/Etoposide for Relapsed Acute Lymphoblastic Leukemia (ALL)
- ClinicalTrials.gov ID
- NCT01230788
- Acronym / sponsor ID
- Rituximab / IRB00039682
- Conditions
- Leukemia, Acute Lymphoblastic Leukemia, ALL
- Keywords
- ALL, Leukemia, Rituximab, Pediatrics
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of enrollment
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Study start
- Sep 2010
- Primary completion
- Oct 2012 (actual)
- Study completion
- Oct 2012 (actual)
- First posted
- 29 Oct 2010 (estimated)
- Results
- Posted 18 Aug 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a pilot study of a drug called rituximab used together with other drugs-prednisone, etoposide, and ifosfamide. Prednisone, etoposide, and ifosfamide have been used as part of standard chemotherapy for relapsed Acute Lymphoblastic Leukemia (ALL). Rituximab was approved by the Food and Drug Administration in 1997. However, the use of rituximab with prednisone, etoposide, and ifosfamide in pediatric patients with relapsed or refractory ALL is considered experimental.
This study is for patients who have ALL in second or greater relapse, or in first relapse and not responding to treatment.
The goals of this study are:
- To see if using rituximab with prednisone, etoposide, and ifosfamide is beneficial to leukemia treatment
- To find out what side effects this combination of drugs can cause
A total of 15 participants (30 years old or younger) will be enrolled, over a period of 2 years.
Detailed description
Rationale for study design:
The combination of etoposide and ifosfamide is a reinduction regimen used in many previous studies for pediatric B lineage acute lymphoblastic leukemia (ALL). It does not use anthracyclines, and therefore can be safely used in patients at risk for cardiac toxicity due to previous anthracycline use.
Previous studies in adult patients with ALL have demonstrated safety and efficacy with the addition of rituximab to other induction regimens. Rituximab is an anti-CD20 monoclonal antibody. Approximately one-half of pediatric cases of B precursor ALL express the CD20 antigen on the leukemic blasts. The use of rituximab provides a potential target for CD20 positive cells, therefore improving the rates of cytotoxicity associated with the chemotherapy. Rituximab has been previously utilized in many pediatric and adult regimens in combination with other chemotherapeutic agents, and is expected to be safe with the combination of etoposide and ifosfamide. However, since it has never been studied with this combination of chemotherapy, strict stopping rules are in place to ensure that it is a safe combination.
A recent study demonstrated upregulation of CD20 expression on leukemic blasts exposed to one week of prednisone therapy. This increase in expression occurred in the majority of B-ALL patient samples, regardless of whether the patient initially expressed CD20 on the surface of the leukemic blasts. In those samples with upregulation of CD20 treated with rituximab, cytotoxicity from rituximab was more successful than in samples with a smaller percentage of CD20 expression.
Therefore, prednisone will be given for two weeks in combination with etoposide and ifosfamide. It is hoped that the percentage of leukemic blasts expressing CD20 will increase with this combination of medications, allowing the rituximab to be more effective when given weekly starting on day 8 of therapy. To better understand this process, samples of blood and bone marrow will be collected to quantify CD20 expression and the amount of leukemia present at multiple time points during the month of study duration.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| rituximab | Experimental | Drug: rituximabstudy drug given |
Who may qualify
- Ages
- 1 year to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (21 listed)
- Age: Patients must be 1-30 years of age at initial diagnosis.
- Diagnosis: Patients must have histologically-confirmed relapsed/refractory Acute Lymphoblastic Leukemia (ALL).
- Disease Status:Patients must be in
- Performance Status: Patients must have a performance status of ≥50 from the Lansky Scale if <10 years or ≥ 50 or from the Karnofsky Scale if ≥ 10 years. Patients who are unable to walk because of paralysis, but who are up in a wheelchair will be considered ambulatory for the purpose of assessing the performance score.
- Prior Therapy: Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study and meet time restrictions from end of prior therapy as stated below:
Key exclusion criteria (8 listed)
- Patients with an active and uncontrolled infection, defined as need for pressors, and/or positive cultures for 24 hours.
- Patients recovering from allogeneic bone marrow transplantation who are still on immunosupressants.
- Pregnant or lactating females. Women of childbearing age will agree to use contraception during the protocol.
- Patients currently receiving other investigational agents, medications, or supplements with a known anti-leukemic effect.
- Patients who, in the opinion of the investigator, will not be able to comply with safety monitoring requirements of the study.
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 |
|---|---|---|
| rituximab375 mg/m2/dose on days 8, 15, 22, and 29 (diluted in NS to a final concentration of 1 mg/ml for ease of administration). (Premedicate with Acetaminophen 15 mg/kg po (max 650 mg) and Diphenhydramine 1 mg/kg IV/PO (max 50 mg)). | Drug | rituximab |
Primary outcome
4 Month Event Free Survival (EFS)
Time frame: one year after enrollment
To estimate the 4 month EFS after therapy with rituximab and cytotoxic chemotherapy (prednisone/etoposide/ifosfamide) in patients with second relapse/refractory ALL.
Toxicities of Rituximab
Time frame: two months after treatment
To describe the toxicities of rituximab in addition to prednisone, etoposide, and ifosfamide.
Remission Induction Rate
Time frame: one month
To estimate the remission induction rate of the addition of rituximab to cytotoxic chemotherapy (prednisone/etoposide/ifosfamide) in patients with second relapse/refractory ALL.
2 secondary outcomes
Minimal Residual Disease
Time frame: one month after treatment
Prednisone Effect
Time frame: one month after treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Dec 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Todd Cooper, DO principal investigator
Emory University/Children's Healthcare of Atlanta
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing rituximab in people with Leukemia and Acute Lymphoblastic Leukemia, run by Emory University at 3 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?
The sponsor lists 21 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: stopped early, as of the sponsor's last update on 1 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Aug 2014). 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?
4 Month Event Free Survival (EFS) (time frame: one year after enrollment). 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 1 Dec 2014.