A Phase I Trial of the Combination of Lenalidomide and Blinatumomab in Patients With Relapsed or Refractory Non-Hodgkins Lymphoma (NHL)
Overview
- Phase
- Phase 1
- Intervention
- Blinatumomab
- Conditions
- Recurrent Burkitt Lymphoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 35
- Locations
- 24
- Primary Endpoint
- Incidence of toxicity
- Status
- Completed
- Last Updated
- 5 months ago
Overview
Brief Summary
This phase I trial studies the side effects and best dose of lenalidomide and blinatumomab when given together in treating patients with non-Hodgkin lymphoma that has returned after a period of improvement (relapsed). Biological therapies, such as lenalidomide, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Blinatumomab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread.
Detailed Description
PRIMARY OBJECTIVE: I. To determine the maximum tolerated dose (MTD) of lenalidomide when given in combination with blinatumomab in the proposed regimen. SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity anti-tumor response (complete response \[CR\] and partial response \[PR\] as per International workshop lymphoma response criteria). II. To investigate the immune response to blinatumomab alone and in combination with lenalidomide. III. To document the infection rate with a 96-hour bag change schedule for blinatumomab. OUTLINE: This is a dose-escalation study of lenalidomide. INDUCTION: Patients receive blinatumomab intravenously (IV) continuously on days 1-56 and lenalidomide orally (PO) on days 29-49 in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients achieving response including stable disease receive blinatumomab IV continuously on days 1-7 and lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receiving response including stable disease after completion of Consolidation receive lenalidomide PO on days 1-21. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 2 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed relapsed cluster of differentiation (CD)19+ non-Hodgkin lymphoma (NHL) (included in this category are follicular grade I, II, III, marginal zone, mantle cell, gray zone, primary mediastinal, Burkitt's, diffuse large B cell, small lymphocytic lymphoma); patients previously treated with CD19-targeted therapy (including chimeric antigen receptor T-cells \[CAR T\]) must have a subsequent biopsy and/or flow cytometry confirming CD19 positivity
- •Karnofsky \>= 60%
- •Life expectancy of greater than 12 weeks
- •Absolute neutrophil count \> 1000/mcL
- •Platelets \>= 50,000/mcL
- •Total bilirubin =\< 1.5 x institutional upper limit of normal
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal
- •AST (SGOT)/ALT(SGPT) (only if elevated liver function tests \[LFTs\] are due to disease) =\< 5.0 x institutional upper limit of normal
- •Body surface area (BSA)-normalized creatinine clearance \>= 60 mL/min/1.73 m\^2 (using Cockcroft-Gault creatinine clearance \[CrCl\])
- •Patients must have had at least two prior chemotherapeutic or biologic (e.g. rituximab alone) regimens and not currently eligible for standard curative options; steroids alone and local radiation do not count as regimens; radiation to \> 1 site and transplant are considered prior regimens
Exclusion Criteria
- •Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- •Patients who are receiving any other investigational agents
- •Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to lenalidomide and blinatumomab or other agents used in study
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Pregnant women are excluded from this study because lenalidomide is an agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with lenalidomide, breastfeeding should be discontinued if the mother is treated with lenalidomide
- •Concurrent use of other anti-cancer agents or treatments
- •Known active hepatitis, type B or C; patients on suppressive therapy with a negative viral load and no evidence of hepatic damage are eligible
- •Prior treatment with lenalidomide within 8 weeks prior to entering the study
Arms & Interventions
Treatment (blinatumomab, lenalidomide)
INDUCTION: Patients receive blinatumomab IV continuously on days 1-56 and lenalidomide PO on days 29-49 in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients achieving response including stable disease receive blinatumomab IV continuously on days 1-7 and lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receiving response including stable disease after completion of Consolidation receive lenalidomide PO on days 1-21. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Intervention: Blinatumomab
Treatment (blinatumomab, lenalidomide)
INDUCTION: Patients receive blinatumomab IV continuously on days 1-56 and lenalidomide PO on days 29-49 in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients achieving response including stable disease receive blinatumomab IV continuously on days 1-7 and lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receiving response including stable disease after completion of Consolidation receive lenalidomide PO on days 1-21. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Intervention: Lenalidomide
Outcomes
Primary Outcomes
Incidence of toxicity
Time Frame: Up to 24 months
Will be graded as according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (version 5.0 beginning April 1, 2018). Toxicities (grade, type, cycle, and attribution) experienced will be listed for each patient and summarized using standard descriptive methods.
Secondary Outcomes
- Clinical anti-tumor response (complete response and partial response as per International workshop lymphoma response criteria)(Up to 24 months)
- Changes in the frequency of CD4+ T cells(Baseline to up to day 57)
- Changes in the production of interferon (INF)-gamma from CD4+ T cells(Baseline to up to day 57)