Nab-paclitaxel/Rituximab-coated Nanoparticle AR160 in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

Sponsor

Mayo Clinic (Other)

Overall Status

Recruiting

CT.gov ID

NCT03003546

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

49.7

Anticipated Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase I trial studies the best dose and side effects of paclitaxel albumin-stabilized nanoparticle formulation (nab-paclitaxel)/rituximab-coated nanoparticle AR160 in treating patients with B-cell non-Hodgkin lymphoma that has come back or is not responding to treatment. Nab-paclitaxel/rituximab-coated nanoparticle AR160 is a combination of paclitaxel albumin-stabilized nanoparticle formulation and rituximab. Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as rituximab, may interfere with the ability of tumor cells to grow and spread. Giving paclitaxel albumin-stabilized nanoparticle formulation and rituximab may work better in treating patients with B-cell non-Hodgkin lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Aggressive Non-Hodgkin Lymphoma CD20 Positive Recurrent B-Cell Non-Hodgkin Lymphoma Recurrent Small Lymphocytic Lymphoma Refractory B-Cell Non-Hodgkin Lymphoma Refractory Small Lymphocytic Lymphoma	Other: Laboratory Biomarker Analysis Drug: Nab-paclitaxel/Rituximab-coated Nanoparticle AR160 Other: Pharmacological Study	Phase 1

Detailed Description

PRIMARY OBJECTIVES:

To establish the maximum tolerated dose (MTD) of nab-paclitaxel/rituximab-coated nanoparticle AR160 (AR160) in patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL). (Phase I)

SECONDARY OBJECTIVES:

To assess the toxicity and safety of AR160. II. To assess complete response rate (CR) progression free survival (PFS), and overall survival (OS) of AR160 with relapsed/refractory B-cell NHL.

TERTIARY OBJECTIVES:

Evaluate pharmacokinetics (PK) of AR160 in two formal PK studies, dose 1 of cycle 1 (48 hours [h] PK analysis) and dose 1 of cycle 2 (24h PK analysis).

OUTLINE: This is a dose-escalation study.

Patients receive nab-paclitaxel/rituximab-coated nanoparticle AR160 intravenously (IV) over 30-60 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for up to 5 years.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

18 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Trial of AR160 (Abraxane/Rituximab 160nm Nanoparticle) in Relapsed/Refractory B Cell Lymphomas Including Transformed Follicular Lymphoma

Actual Study Start Date :

Apr 25, 2019

Anticipated Primary Completion Date :

Jun 15, 2023

Anticipated Study Completion Date :

Jun 15, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (AR160) Patients receive nab-paclitaxel/rituximab-coated nanoparticle AR160 IV over 30-60 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis Correlative studies Drug: Nab-paclitaxel/Rituximab-coated Nanoparticle AR160 Given IV Other Names: AR160 Other: Pharmacological Study Correlative studies

Arm

Intervention/Treatment

Experimental: Treatment (AR160)

Patients receive nab-paclitaxel/rituximab-coated nanoparticle AR160 IV over 30-60 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis

Correlative studies

Drug: Nab-paclitaxel/Rituximab-coated Nanoparticle AR160

Given IV

Other Names:

AR160

Other: Pharmacological Study

Correlative studies

Outcome Measures

Primary Outcome Measures

MTD defined as the highest dose level patients develop a dose limiting toxicity assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [Up to 28 days]
The maximum grade of each type of toxicity will be recorded for each patient. For each toxicity reported by dose level, the percentage of patients developing any degree of that toxicity as well as the percentage of patients developing a severe degree (grade 3 or higher) will be determined.

Secondary Outcome Measures

OS [Up to 5 years]
A table will be constructed to display by dose level, the number of patients treated at that dose level, the number of cycle of treatment administered, DLT observed, progression-free survival time and overall survival time.
PFS [Up to 5 years]
A table will be constructed to display by dose level, the number of patients treated at that dose level, the number of cycle of treatment administered, DLT observed, progression-free survival time and overall survival time.
Tumor response assessed using The Lugano Classification Response criteria [Up to 5 years]
A table will be constructed to display by dose level, the number of patients treated at that dose level, the number of cycle of treatment administered, DLT observed, progression-free survival time and overall survival time.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histological confirmation of relapsed/refractory B-cell NHL, CD20+
NOTE: patients with small lymphocytic lymphoma (SLL) are eligible however patients with chronic lymphocytic leukemia (CLL) are not eligible
Waldenstrom macroglobulinemia patients are not eligible; aggressive lymphoma patients who are transplant eligible must have undergone a transplant
The biopsy confirming relapse can be up to 24 weeks prior to registration as long as there is no intervening therapy
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
Absolute neutrophil count (ANC) >= 1500/mm^3
Platelet count >= 75,000/mm^3
Hemoglobin >= 8.0 g/dL
Total bilirubin =< 1.5 X upper limit of normal (ULN) or if total bilirubin is > 1.5 X ULN, the direct bilirubin =< ULN
Alkaline phosphatase =< 3 X ULN unless due to direct lymphoma involvement, and then =< 5 X ULN
Aspartate transaminase (AST) =< 3 X ULN unless due to direct lymphoma involvement, and then =< 5 X ULN
Calculated creatinine clearance must be >= 30 ml/min using the Cockcroft-Gault formula
Life expectancy >= 3 months
Ability to provide written informed consent
Willing to return to enrolling institution for follow-up (during the treatment and observation phases of the study)
Willing to provide tissue for central review blood samples for correlative research purposes
No other therapy with demonstrated clinical benefit in relapsed/refractory B-cell NHL available to the patient
Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only

Exclusion Criteria:

Any of the following:
Pregnant women
Nursing women
Men or women of childbearing potential who are unwilling to employ adequate contraception
Active central nervous system (CNS) lymphoma or cerebrospinal fluid involvement with malignant lymphoma cells that requires therapy
Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
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
Patients who received most recent therapy =< 4 weeks prior to registration; NOTE: use of systemic steroid therapy is allowed pretreatment
Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
Patients must be disease-free of prior invasive malignancies for > 5 years prior to registration with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
Patients with >= 25% of the bone marrow radiated for other diseases
Other medical conditions including but not limited to:
History of liver disease such as cirrhosis, chronic active hepatitis, chronic persistent hepatitis or hepatitis B or C
Active infection requiring parenteral antibiotics
New York Heart Association class II-IV congestive heart failure (serious cardiac arrhythmia requiring medication)
Myocardial infarction or unstable angina =< 6 months prior to registration
Congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
Clinically significant peripheral vascular disease
History of CNS disease (e.g., primary brain tumor, vascular abnormalities, etc.), clinically significant stroke or transient ischemic attack (TIA) =< 6 months prior to registration, seizures not controlled with standard medical therapy
Neuropathy ˃ grade 3
Administration of strong CYP2C8 or CYP3A4 inhibitors or inducers =< 10 days prior to registration