Rituximab for Patients With Relapsed Acute Lymphoblastic Leukemia

• Status: Terminated
• Trial end date: 2012-10-01
• Target enrollment: 0
• Participant gender: All

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). 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.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Emory University
• Treatments: Rituximab

Criteria

Inclusion Criteria:

1. Age: Patients must be 1-30 years of age at initial diagnosis.

2. Diagnosis: Patients must have histologically-confirmed relapsed/refractory Acute Lymphoblastic Leukemia (ALL).

3. 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).

4. 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.

5. 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.

6. Institutional review board approval.

7. Individual informed consent per local guidelines and federal and state regulations.

8. 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.

Exclusion Criteria:

1. Patients with an active and uncontrolled infection, defined as need for pressors, and/or positive cultures for 24 hours.

2. Patients recovering from allogeneic bone marrow transplantation who are still on immunosupressants.

3. Pregnant or lactating females. Women of childbearing age will agree to use contraception during the protocol.

4. Patients currently receiving other investigational agents, medications, or supplements with a known anti-leukemic effect.

5. Patients who, in the opinion of the investigator, will not be able to comply with safety monitoring requirements of the study.

6. Patients with reactivation of hepatitis B prior to starting therapy.

7. Patients who are HIV positive.

8. Patients must not have CNS 3 involvement.