Dose Adjusted EPOCH Regimen in Combination With Ofatumumab or Rituximab in Treating Patients With Newly Diagnosed or Relapsed or Refractory Burkitt Lymphoma or Relapsed or Refractory Acute Lymphoblastic Leukemia

Refractory Acute Lymphoblastic Leukemia Clinical Trial

Official title:

Phase II Study of the Dose Adjusted EPOCH Regimen in Combination With Ofatumumab/Rituximab as Therapy for Patients With Newly Diagnosed or Relapsed/Refractory Burkitt Leukemia or Relapsed/Refractory Acute Lymphoblastic Leukemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02199184
• Other study ID #: 2014-0123
• Secondary ID: NCI-2014-0170720
• Status: Completed
• Phase: Phase 2
• Start date: January 14, 2015
• Est. completion date: February 17, 2023

Study information

• Verified date: May 2024
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial studies how well a dose adjusted regimen consisting of etoposide, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride (EPOCH) works in combination with ofatumumab or rituximab in treating patients with Burkitt lymphoma that is newly diagnosed, or has returned after a period of improvement (relapsed), or has not responded to previous treatment (refractory) or relapsed or refractory acute lymphoblastic leukemia. Drugs used in chemotherapy, such as etoposide, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as ofatumumab and rituximab, may interfere with the ability of cancer cells to grow and spread. Giving more than one drug (combination chemotherapy) together with monoclonal antibody therapy may kill more cancer cells.

Description:

PRIMARY OBJECTIVE:

I. To evaluate the clinical efficacy of the combination of dose adjusted (DA)-EPOCH + ofatumumab in patients with newly diagnosed or relapsed/refractory Burkitt leukemia or relapsed/refractory acute lymphoblastic leukemia (ALL) defined by complete response rate.

SECONDARY OBJECTIVE:

I. To evaluate the safety of this combination, the overall survival and event-free survival rates.

OUTLINE:

Patients receive DA-EPOCH regimen comprising doxorubicin hydrochloride intravenously (IV), vincristine sulfate IV, and etoposide IV continuously over 96 hours on days 1-4; cyclophosphamide IV over 1-2 hours on day 5; and prednisone orally (PO) twice daily (BID) on days 1-5. Patients also receive ofatumumab IV over 2 hours on days 1, 2, and 11 of cycle 1; on days 1 and 8 of cycles 2 and 4; and on days 1 and 11 of cycle 3 for a total of 9 injections. Patients may receive rituximab instead of ofatumumab if their insurance provider does not cover the cost of ofatumumab. Patients receive rituximab IV over 2 hours on days 1 and 11 of cycles 1 and 3 and on days 2 and 8 of cycles 2 and 4. Treatment repeats every 21-28 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 2-4 months for 1 year and then every 4-8 months for 2 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: February 17, 2023
• Est. primary completion date: February 17, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Burkitt's or Burkitt-like leukemia/lymphoma, either previously untreated, or relapsed/refractory, or human immunodeficiency virus (HIV)-related; patients with double or triple hit high-grade leukemia/lymphoma are eligible also; patients HIV positive will be described and reported separately or relapsed/refractory acute lymphoblastic leukemia (ALL).

• Zubrod performance status =< 3 (Eastern Cooperative Oncology Group [ECOG] scale)

• Creatinine less than or equal to 2.0 mg/dL (unless considered tumor related)

• Bilirubin less than or equal to 2.0 mg/dL (unless considered tumor related)

• Adequate cardiac function defined as no history of clinically significant arrhythmia, or history of myocardial infarction (MI) within 3 months prior to study enrollment; cardiac function will be assessed by history and physical examination

Exclusion Criteria:

• Pregnant or nursing women

• Active and uncontrolled disease/infection as judged by the treating physician

• Unable or unwilling to sign the consent form

• Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)

Related Conditions & MeSH terms

• AIDS-Related Burkitt Lymphoma
• Atypical Burkitt/Burkitt-Like Lymphoma
• Burkitt Lymphoma
• High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements
• High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements
• Leukemia
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, B-Cell
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Recurrence
• Recurrent Acute Lymphoblastic Leukemia
• Recurrent Burkitt Lymphoma
• Refractory Acute Lymphoblastic Leukemia
• Refractory Burkitt Lymphoma

Intervention

Drug:
• Cyclophosphamide
Given IV
• Doxorubicin Hydrochloride
Given IV
• Etoposide
Given IV

Biological:
• Ofatumumab
Given IV

Drug:
• Prednisone
Given PO

Biological:
• Rituximab
Given IV

Drug:
• Vincristine Sulfate
Given IV

Locations

Country	Name	City	State
United States	M D Anderson Cancer Center	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Participants With a Response	Complete Remission: Normalization of the peripheral blood and bone marrow with 5% or less blasts in a normocellular or hypercellular marrow with a granulocyte count of 1 x 109/L or above and platelet count of 100 x 10^9/L or above. Complete resolution of all sites of extramedullary disease is required for CR.	Up to 8 years
Secondary	Overall Survival Time	Time from date of treatment start until date of death due to any cause or last Follow-up.	Up to 8 years
Secondary	Event-free Survival	Time from date of treatment start until the date of first objective documentation of disease-relapse.	Up to 8 years
Secondary	Complete Response Duration	Response date to loss of response or last follow up.	Up to 8 years

External Links

•   MD Anderson Cancer Center