Rituximab for Patients With Relapsed Acute Lymphoblastic Leukemia (Rituximab)
|ClinicalTrials.gov Identifier: NCT01230788|
Recruitment Status : Terminated (Lack of enrollment)
First Posted : October 29, 2010
Results First Posted : August 18, 2014
Last Update Posted : December 1, 2014
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.
|Condition or disease||Intervention/treatment||Phase|
|Leukemia Acute Lymphoblastic Leukemia ALL||Drug: rituximab||Not Applicable|
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||1 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Trial of Rituximab Combined With Prednisone/Ifosfamide/Etoposide for Relapsed Acute Lymphoblastic Leukemia (ALL)|
|Study Start Date :||September 2010|
|Actual Primary Completion Date :||October 2012|
|Actual Study Completion Date :||October 2012|
study drug given
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)).
- 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.
- Minimal Residual Disease [ Time Frame: one month after treatment ]To perform serial minimal residual disease (MRD) measurements to provide an objective determination of the effectiveness of this therapy.
- Prednisone Effect [ Time Frame: one month after treatment ]To correlate the effect of prednisone on CD20 expression using serial measurements of CD20 expression in leukemic blasts.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01230788
|United States, Georgia|
|Children's Healthcare of Atlanta|
|Atlanta, Georgia, United States, 30322|
|Atlanta, Georgia, United States, 30322|
|United States, Missouri|
|The children's Mercy Hospital|
|Kansas City, Missouri, United States, 64108|
|Principal Investigator:||Todd Cooper, DO||Emory University/Children's Healthcare of Atlanta|