A Phase II Trial Using Meloxicam Plus Filgrastim in Patients With Multiple Myeloma and Non-Hodgkin's Lymphoma

Study Overview
=================
Brief Summary
-----------------
The trial is an open label Simon optimal two-stage Phase II trial of fixed doses of oral meloxicam and subcutaneous filgrastim to assess the safety and efficacy in mobilizing autologous peripheral blood stem cells (PBSC) from multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL) patients planning to undergo high-dose chemotherapy with stem cell support. Clinical data regarding the cellular composition and function of the graft mobilized by this combination will be obtained.

Official Title
-----------------
A Phase II Trial of Prostaglandin E2 Inhibition, Using Meloxicam, Plus Filgrastim for Mobilization of Autologous Peripheral Blood Stem Cells in Patients With Multiple Myeloma and Non-Hodgkin's Lymphoma

Conditions
-----------------
Multiple Myeloma, Non-Hodgkin's Lymphoma

Intervention / Treatment
-----------------
* Drug: Meloxicam
* Drug: Filgrastim


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: A patient must meet all of the following inclusion criteria to be eligible for enrollment in this study: Has provided written informed consent prior to completing any study procedures. Patients must have a previously documented histologic diagnosis of multiple myeloma (MM) or non-Hodgkin's lymphoma (NHL), and be eligible to undergo autologous PBSC transplantation on institutional protocols. Multiple myeloma should be in first or second partial response or better, as defined by International Myeloma Working Group criteria.50 Non-Hodgkin's lymphoma must be in either first or second partial response or better and have any one of the following histologies: Diffuse large B cell lymphoma Transformed lymphoma Mantle cell lymphoma Follicular lymphoma (any grade) Peripheral T cell lymphoma Age ≥18 to ≤75 years at time of consent. Karnofsky performance status of at least 70%. Adequate organ function defined as: Left ventricular ejection fraction ≥45% Corrected DLCO ≥50% Serum bilirubin, AST (aspartate aminotransferase) and ALT(alanine aminotransferase) ≤ twice the upper limit of normal Serum creatinine ≤ 2.0 mg/dl Urine M-protein ≤1 g/24 hours (MM patients only) No prior attempt at mobilizing PBSC. Patients must be at least 4 weeks from last cytotoxic chemotherapy (including alkylating, anthracyclines, epipodophylatoxins, and platinum drugs), or immunomodulatory drugs (including lenalidomide or pomalidomide, or related derivatives) at time of treatment on this protocol. Patients must be at least 2 weeks from last treatment with a proteasome inhibitor (e.g., bortezomib, carfilzomib) at time of treatment on this protocol. Patients must be negative for HIV. Women of childbearing potential must have a negative pregnancy test (urine or serum) and must not be lactating at the time of informed consent. Women and men must use adequate birth control while taking part in this study (such as a condom or diaphragm with contraceptive cream/jelly, birth control pills, Norplant, abstinence (no sexual intercourse) or surgical sterilization. Exclusion Criteria: Exclude a patient if any of the following conditions are observed: Patients must not have received radiation therapy within the past 4 weeks, and not to more than 20% of hematopoiesis forming bones (spine, pelvis and proximal long bones). Patients must not have active central nervous system involvement. Patients must not have a prior autologous, syngeneic or allogeneic hematopoietic stem cell transplant. Patients must not have received prior bone seeking radionuclides. Patients must not have received myeloid growth factors within 2 weeks before mobilization attempt on this study. Patients must not have taken nonsteroidal antiinflammatory drugs (NSAID) in the past 14 days before treatment on this protocol. Patients must not have nor had active or recent peptic ulcer disease within the past 6 months. a) Patients with active significant symptoms of dyspepsia will be excluded. Patients with a history of asthma will be excluded because of the potential for NSAID to precipitate asthma in these patients.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Treatment<br>Meloxicam and Filgrastim will be administered in fixed doses to each patient enrolled on this study. The treatments will be administered in a staggered dose schedule for a total treatment duration of 7 days prior to apheresis. 15 mg tablets of Meloxicam will be taken orally for 5 consecutive days. 10 µg/kg of Filgrastim will be subcutaneously injected for 5 consecutive days. Filgrastim may be subcutaneously injected for an additional 3 days if patients do not meet the primary endpoint for cell collection. | Drug: Meloxicam<br>* 15 mg tablets of Meloxicam will be taken orally in the morning, with or without food.<br>* Other names: Mobic;Drug: Filgrastim<br>* Filgrastim will be subcutaneously injected in one or two sites at home.<br>* Other names: Neupogen;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Patients Who Mobilize and Collect at Least Half of the Total Target CD34+ Cell Dose in the First Apheresis | Percent of patients who mobilize and collect at least half of the total target CD34+ cell dose in the first apheresis with binomial exact confidence intervals according to disease: Multiple myeloma patients: percent of patients with >= 5x106 CD34 cells/kg in the first day's apheresis. Non-Hodgkin's lymphoma patients: percent of patients with >= 2.5x106 CD34 cells/kg in the first day's apheresis. | within 100 days of transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Treatment Related Adverse Events Grade 3 or Higher for Nonhematological Toxicity | Number of unique patients who had a treatment related (possible, probable or definite) non-hematological adverse event that was graded 3 or greater using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. | within 100 days of transplant | 
| Summary Statistics for Graft Composition of Peripheral Blood Stem Cell Collection at Each Time Point | Mean and Standard Deviation of the Graft Composition of Peripheral Blood Stem Cell Collection (CD34 (x10^6cells/kg)) at each time point collected during Cycle 2. | Cycle 2, Days 1-4, within 100 days of transplant | 
| Time to Neutrophil Engraftment | Time to neutrophil engraftment will be analyzed by the Kaplan-Meier method. The time to engraftment of neutrophils is defined as the time from day 0 to the date of the first of three consecutive days after transplantation during which the absolute neutrophils count (ANC) is at least 0.5 x109/l. The median and 95% confidence intervals will be provided. Only patients with neutrophil engraftment will be included. | within 100 days of transplant | 
| Time to Platelet Engraftment | Time to platelet engraftment will be analyzed by the Kaplan-Meier method. The time to engraftment of platelets is defined as the time from day 0 to the first of seven consecutive Complete Blood Counts (CBCs) obtained on different days after transplantation during which the platelet count is at least 20 x109/l. The CBCs obtained should be at least seven days after the most recent platelet transfusion. The median and 95% confidence intervals will be provided. Only patients achieving platelet engraftment will be included. | within 100 days of transplant |