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

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

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.

Study Overview

• Status: Completed
• Conditions: Recurrent Acute Lymphoblastic Leukemia; Refractory Acute Lymphoblastic Leukemia; Recurrent Burkitt Lymphoma; AIDS-Related Burkitt Lymphoma; Atypical Burkitt/Burkitt-Like Lymphoma; High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements; High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements; Refractory Burkitt Lymphoma
• Intervention / Treatment: Drug: Etoposide; Drug: Cyclophosphamide; Drug: Prednisone; Drug: Vincristine Sulfate; Drug: Doxorubicin Hydrochloride; Biological: Rituximab; Biological: Ofatumumab

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (DA-EPOCH and ofatumumab or rituximab); Patients receive DA-EPOCH regimen comprising doxorubicin hydrochloride 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 PO 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.

Drug: Etoposide; Given IV; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16; VP 16-213; VP-16; VP-16-213; VP16; Drug: Cyclophosphamide; Given IV; Other Names: Cytoxan; CTX; (-)-Cyclophosphamide; 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate; Carloxan; Ciclofosfamida; Ciclofosfamide; Cicloxal; Clafen; Claphene; CP monohydrate; CYCLO-cell; Cycloblastin; Cycloblastine; Cyclophospham; Cyclophosphamid monohydrate; Cyclophosphamide Monohydrate; Cyclophosphamidum; Cyclophosphan; Cyclophosphane; Cyclophosphanum; Cyclostin; Cyclostine; Cytophosphan; Cytophosphane; Fosfaseron; Genoxal; Genuxal; Ledoxina; Mitoxan; Neosar; Revimmune; Syklofosfamid; WR- 138719; Drug: Prednisone; Given PO; Other Names: Deltasone; Orasone; .delta.1-Cortisone; 1, 2-Dehydrocortisone; Adasone; Cortancyl; Dacortin; DeCortin; Decortisyl; Decorton; Delta 1-Cortisone; Delta-Dome; Deltacortene; Deltacortisone; Deltadehydrocortisone; Deltison; Deltra; Econosone; Lisacort; Meprosona-F; Metacortandracin; Meticorten; Ofisolona; Panafcort; Panasol-S; Paracort; Perrigo Prednisone; PRED; Predicor; Predicorten; Prednicen-M; Prednicort; Prednidib; Prednilonga; Predniment; Prednisone Intensol; Prednisonum; Prednitone; Promifen; Rayos; Servisone; SK-Prednisone; Drug: Vincristine Sulfate; Given IV; Other Names: Oncovin; Kyocristine; Leurocristine Sulfate; Leurocristine, sulfate; Vincasar; Vincosid; Vincrex; Vincristine, sulfate; Drug: Doxorubicin Hydrochloride; Given IV; Other Names: Adriamycin; 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI); ADM; Adriacin; Adriamycin Hydrochloride; Adriamycin PFS; Adriamycin RDF; ADRIAMYCIN, HYDROCHLORIDE; Adriamycine; Adriblastina; Adriblastine; Adrimedac; Chloridrato de Doxorrubicina; DOX; DOXO-CELL; Doxolem; Doxorubicin HCl; Doxorubicin.HCl; Doxorubin; Farmiblastina; FI 106; FI-106; hydroxydaunorubicin; Rubex; Biological: Rituximab; Given IV; Other Names: Rituxan; MabThera; ABP 798; BI 695500; C2B8 Monoclonal Antibody; Chimeric Anti-CD20 Antibody; CT-P10; IDEC-102; IDEC-C2B8; IDEC-C2B8 Monoclonal Antibody; Monoclonal Antibody IDEC-C2B8; PF-05280586; Riabni; Rituximab ABBS; Rituximab ARRX; Rituximab Biosimilar ABP 798; Rituximab Biosimilar BI 695500; Rituximab Biosimilar CT-P10; Rituximab Biosimilar GB241; Rituximab Biosimilar IBI301; Rituximab Biosimilar JHL1101; Rituximab Biosimilar PF-05280586; Rituximab Biosimilar RTXM83; Rituximab Biosimilar SAIT101; Rituximab Biosimilar SIBP-02; rituximab biosimilar TQB2303; Rituximab PVVR; rituximab-abbs; Rituximab-arrx; Rituximab-pvvr; RTXM83; Ruxience; Truxima; Biological: Ofatumumab; Given IV; Other Names: Kesimpta; Arzerra; HuMax-CD20; GSK1841157; HuMax-CD20, 2F2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response rates	Will be estimated along with the 95% credible intervals.	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	Safety data will be summarized using frequency and percentage.	Up to 3 years
Overall survival time	Will be estimated using the Kaplan-Meier method.	Up to 3 years
Event-free survival	Will be estimated using the Kaplan-Meier method.	Up to 3 years
Complete response duration	Will be estimated using the Kaplan-Meier method.	Up to 3 years

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Elias Jabbour, MD, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• MD Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2015
• Primary Completion (Actual): February 17, 2023
• Study Completion (Actual): February 17, 2023

Study Registration Dates

• First Submitted: July 22, 2014
• First Submitted That Met QC Criteria: July 23, 2014
• First Posted (Estimated): July 24, 2014

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 18, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Infections; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Disease Attributes; DNA Virus Infections; Tumor Virus Infections; Epstein-Barr Virus Infections; Herpesviridae Infections; Lymphoma; Lymphoma, B-Cell; Leukemia; Recurrence; Burkitt Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Dermatologic Agents; Antibiotics, Antineoplastic; Keratolytic Agents; Cyclophosphamide; Etoposide; Etoposide phosphate; Antibodies; Podophyllotoxin; Immunoglobulins; Rituximab; Ofatumumab; Prednisone; Doxorubicin; Liposomal doxorubicin; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Vincristine; Cortisone
• Other Study ID Numbers: 2014-0123 (Other Identifier: M D Anderson Cancer Center); NCI-2014-01707 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No