Combination Chemotherapy and Ofatumumab in Treating Patients With Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

Phase II Study of the Hyper - CVAD Regimen in Combination With Ofatumumab as Frontline Therapy for Patients With CD-20 Positive Acute Lymphoblastic Leukemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01363128
• Other study ID #: 2010-0708
• Secondary ID: NCI-2011-0106120
• Status: Completed
• Phase: Phase 2
• Start date: July 12, 2011
• Est. completion date: April 8, 2020

Study information

• Verified date: April 2021
• 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 combination chemotherapy and ofatumumab work in treating patients with acute lymphoblastic leukemia or lymphoblastic lymphoma. Drugs used in chemotherapy, such as cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone, 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. Immunotherapy with ofatumumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving combination chemotherapy together with ofatumumab may be an effective treatment for acute lymphoblastic leukemia or lymphoblastic lymphoma.

Description:

PRIMARY OBJECTIVES:

I. To evaluate the clinical efficacy of the combination of hyper-CVAD (cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone) + ofatumumab in patients with newly diagnosed acute lymphoblastic leukemia with any level of CD20 expression: event-free survival; overall response rate; overall survival.

SECONDARY OBJECTIVES:

I. To evaluate the safety of this combination.

OUTLINE:

COURSES 1, 3, 5, 7: Patients receive hyper-CVAD comprising cyclophosphamide intravenously (IV) over 3 hours every 12 hours on days 1-3; doxorubicin hydrochloride IV over 24 hours on day 4; vincristine sulfate IV over 15 minutes on days 4 and 11; and dexamethasone IV over 30 minutes or orally (PO) once daily (QD) on days 1-4 and 11-14. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 11 of courses 1 and 3.

COURSES 2, 4, 6, 8: Patients receive high-dose methotrexate IV over 2 hours and then over 22 hours on day 1 and cytarabine IV over 2 hours every 12 hours on days 2-3. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 8 of courses 2 and 4.

Treatment repeats every 21-28 days for 8 courses in the absence of disease progression or unacceptable toxicity. Patients may receive maintenance therapy for an additional 30 months.

After completion of study treatment, patients are followed up at 30 days and then every 3 months for 1 year.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: April 8, 2020
• Est. primary completion date: April 8, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Patients of all ages with newly diagnosed, previously untreated CD-20+ acute lymphoblastic leukemia (ALL), or lymphoblastic lymphoma, Burkitt leukemia/lymphoma or having achieved complete remission (CR) with one course of induction chemotherapy

• Failure to one induction course of chemotherapy (these patients will be analyzed separately)

• Performance status of 0, 1, or 2

• Creatinine less than or equal to 3.0 mg/dL (unless considered tumor related)

• Bilirubin less than or equal to 3.0 mg/dL (unless considered tumor related)

• Adequate cardiac function defined as no clinically significant history of arrhythmia as determined by the principal investigator (PI) and/or the treating physician, history of myocardial infarction (MI) or clinically significant abnormal electrocardiogram (EKG), as determined by the PI and/or the treating physician, within 3 months prior to study enrollment; cardiac function will be assessed by history and physical examination

• No active or co-existing malignancy (other than ALL or lymphoblastic lymphoma) with life expectancy less than 12 months due to that malignancy

Exclusion Criteria:

• Pregnant or nursing women

• Known to be human immunodeficiency virus positive (HIV+)

• Philadelphia chromosome (Ph)+ ALL

• 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)

• Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half-lives (calculated by multiplying the reported terminal half-life by 5) or 4 weeks prior to enrollment, whichever is longer, or currently participating in any other interventional clinical study

• History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae

• Positive serology for hepatitis B (HB) defined as a positive test for hepatitis B surface antigen (HBsAg); in addition, if negative for HBsAg but hepatitis B core antibody (HBcAb) positive (regardless of HBsAb status), a HB deoxyribonucleic acid (DNA) test will be performed and if positive the subject will be excluded; consult with a physician experienced in care & management of subjects with hepatitis B to manage/treat subjects who are anti-HBc positive

• Positive serology for hepatitis C (HC) defined as a positive test for hepatitis C antibody (HCAb), in which case reflexively perform a HC radioimmunoblotting assay (RIBA) immunoblot assay on the same sample to confirm the result

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Adult Acute Lymphoblastic Leukemia in Complete Remission
• Burkitt Leukemia
• Burkitt Lymphoma
• CD20 Positive
• Childhood Acute Lymphoblastic Leukemia in Complete Remission
• Leukemia
• Leukemia, Lymphoid
• Lymphoblastic Lymphoma
• Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Cyclophosphamide
Given IV
• Cytarabine
Given IV
• Dexamethasone
Given IV or PO
• Doxorubicin Hydrochloride
Given IV

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Methotrexate
Given IV

Biological:
• Ofatumumab
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	Number of Participants With Complete Remission (CR)	Complete Remission is Normalization of the peripheral blood and bone marrow with 5% or less blasts in marrow with a granulocyte count of 1 x 109/L or above and a platelet count of 100x 109/L or above. Complete resolution of all sites of extramedullary disease is required for CR.	Up to 8 years
Primary	4-Year Overall Survival	Overall Survival is defined as time from date of treatment start until date of death due to any cause or last Follow-up. For continuous data, summary statistics including n, mean, standard deviation, median, minimum and maximum will be computed. The posterior median time to event and it 95% credible interval will be estimated. Kaplan-Meier method, Log rank test and Cox proportional hazards regression modeling will be utilized to analyze survival at 4 years.	Up to 4 years
Primary	4-year Event Free Survival	Event Free Survival defined as the time from the start of therapy to time of primary refractory disease, relapse from CR, death from any cause or last follow-up. Kaplan-Meier method will be utilized to analyze event free survival for the 4 year percent alive and in CR.	Up to 4 years

External Links

•   University of Texas MD Anderson Cancer Center Website