Multiple Myeloma, Non-Hodgkin's Lymphoma
Conditions
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.
Interventions
DRUGMeloxicam
15 mg tablets of Meloxicam will be taken orally in the morning, with or without food.
DRUGFilgrastim
Filgrastim will be subcutaneously injected in one or two sites at home.
Sponsors
National Cancer Institute (NCI)
Sherif S. Farag
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
A patient must meet all of the following inclusion criteria to be eligible for enrollment in this study: 1. Has provided written informed consent prior to completing any study procedures. 2. 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. 1. Multiple myeloma should be in first or second partial response or better, as defined by International Myeloma Working Group criteria.50 2. 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 3. Age ≥18 to ≤75 years at time of consent. 4. Karnofsky performance status of at least 70%. 5. Adequate organ function defined as: 1. Left ventricular ejection fraction ≥45% 2. Corrected DLCO ≥50% 3. Serum bilirubin, AST (aspartate aminotransferase) and ALT(alanine aminotransferase) ≤ twice the upper limit of normal 4. Serum creatinine ≤ 2.0 mg/dl 5. Urine M-protein ≤1 g/24 hours (MM patients only) 6. No prior attempt at mobilizing PBSC. 7. 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. 8. 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. 9. Patients must be negative for HIV. 10. Women of childbearing potential must have a negative pregnancy test (urine or serum) and must not be lactating at the time of informed consent. 1. 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: 1. 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). 2. Patients must not have active central nervous system involvement. 3. Patients must not have a prior autologous, syngeneic or allogeneic hematopoietic stem cell transplant. 4. Patients must not have received prior bone seeking radionuclides. 5. Patients must not have received myeloid growth factors within 2 weeks before mobilization attempt on this study. 6. Patients must not have taken nonsteroidal antiinflammatory drugs (NSAID) in the past 14 days before treatment on this protocol. 7. 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. 8. Patients with a history of asthma will be excluded because of the potential for NSAID to precipitate asthma in these patients.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Patients Who Mobilize and Collect at Least Half of the Total Target CD34+ Cell Dose in the First Apheresis | within 100 days of transplant | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Treatment Related Adverse Events Grade 3 or Higher for Nonhematological Toxicity | within 100 days of transplant | 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. |
| Summary Statistics for Graft Composition of Peripheral Blood Stem Cell Collection at Each Time Point | Cycle 2, Days 1-4, within 100 days of transplant | 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. |
| Time to Neutrophil Engraftment | within 100 days of transplant | 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. |
| Time to Platelet Engraftment | within 100 days of transplant | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Multiple Myeloma This is for the patients with Multiple Myeloma.
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.
Meloxicam: 15 mg tablets of Meloxicam will be taken orally in the morning, with or without food.
Filgrastim: Filgrastim will be subcutaneously injected in one or two sites at home. | 25 |
| Non Hodgkins Lymphoma This is for the patients with Non Hodgkins Lymphoma.
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.
Meloxicam: 15 mg tablets of Meloxicam will be taken orally in the morning, with or without food.
Filgrastim: Filgrastim will be subcutaneously injected in one or two sites at home. | 13 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Multiple Myeloma | Non Hodgkins Lymphoma | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 2 Participants | 11 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants | 11 Participants | 27 Participants |
| Age, Continuous | 61.1 years STANDARD_DEVIATION 8.6 | 51.2 years STANDARD_DEVIATION 16.1 | 57.8 years STANDARD_DEVIATION 12.5 |
| Disease Status at Registration Complete Remission | 1 Participants | 9 Participants | 10 Participants |
| Disease Status at Registration Complete Remission Confirmed | 0 Participants | 1 Participants | 1 Participants |
| Disease Status at Registration Partial Response | 19 Participants | 0 Participants | 19 Participants |
| Disease Status at Registration Partial Response without prior Complete Response | 0 Participants | 1 Participants | 1 Participants |
| Disease Status at Registration Unknown | 0 Participants | 1 Participants | 1 Participants |
| Disease Status at Registration Very Good Partial Response | 5 Participants | 1 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants | 11 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) White | 21 Participants | 10 Participants | 31 Participants |
| Sex: Female, Male Female | 12 Participants | 5 Participants | 17 Participants |
| Sex: Female, Male Male | 13 Participants | 8 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 25 | 1 / 13 |
| other Total, other adverse events | 10 / 25 | 10 / 13 |
| serious Total, serious adverse events | 1 / 25 | 1 / 13 |
Outcome results
Primary
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.
Time frame: within 100 days of transplant
Population: Patients with available post-transplant CD34+ results.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Multiple Myeloma | Percent of Patients Who Mobilize and Collect at Least Half of the Total Target CD34+ Cell Dose in the First Apheresis | 32.0 percentage of participants |
| Non Hodgkins Lymphoma | Percent of Patients Who Mobilize and Collect at Least Half of the Total Target CD34+ Cell Dose in the First Apheresis | 58.3 percentage of participants |
Secondary
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.
Time frame: within 100 days of transplant
Population: All patients who received a transplant.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Multiple Myeloma | Number of Patients With Treatment Related Adverse Events Grade 3 or Higher for Nonhematological Toxicity | 0 Participants |
| Non Hodgkins Lymphoma | Number of Patients With Treatment Related Adverse Events Grade 3 or Higher for Nonhematological Toxicity | 0 Participants |
Secondary
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.
Time frame: Cycle 2, Days 1-4, within 100 days of transplant
Population: Patients with available post-transplant CD34 (x10\^6/kg) data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Multiple Myeloma | Summary Statistics for Graft Composition of Peripheral Blood Stem Cell Collection at Each Time Point | Cycle 2 Day 1 | 3.42 x10^6cells/kg | Standard Deviation 2.72 |
| Multiple Myeloma | Summary Statistics for Graft Composition of Peripheral Blood Stem Cell Collection at Each Time Point | Cycle 2 Day 2 | 4.92 x10^6cells/kg | Standard Deviation 2.86 |
| Multiple Myeloma | Summary Statistics for Graft Composition of Peripheral Blood Stem Cell Collection at Each Time Point | Cycle 2 Day 3 | 2.63 x10^6cells/kg | Standard Deviation 1.7 |
| Multiple Myeloma | Summary Statistics for Graft Composition of Peripheral Blood Stem Cell Collection at Each Time Point | Cycle 2 Day 4 | 1.55 x10^6cells/kg | Standard Deviation 0.35 |
| Non Hodgkins Lymphoma | Summary Statistics for Graft Composition of Peripheral Blood Stem Cell Collection at Each Time Point | Cycle 2 Day 4 | 0.90 x10^6cells/kg | — |
| Non Hodgkins Lymphoma | Summary Statistics for Graft Composition of Peripheral Blood Stem Cell Collection at Each Time Point | Cycle 2 Day 1 | 3.22 x10^6cells/kg | Standard Deviation 2.2 |
| Non Hodgkins Lymphoma | Summary Statistics for Graft Composition of Peripheral Blood Stem Cell Collection at Each Time Point | Cycle 2 Day 3 | 0.89 x10^6cells/kg | Standard Deviation 0.45 |
| Non Hodgkins Lymphoma | Summary Statistics for Graft Composition of Peripheral Blood Stem Cell Collection at Each Time Point | Cycle 2 Day 2 | 3.51 x10^6cells/kg | Standard Deviation 2.67 |
Secondary
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.
Time frame: within 100 days of transplant
Population: All patients who had a transplant and engrafted. All patients were analyzed together since the definition for neutrophil engraftment is the same regardless of disease and only the time until overall neutrophil engraftment was the outcome of interest.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Multiple Myeloma | Time to Neutrophil Engraftment | 13.0 days |
Secondary
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.
Time frame: within 100 days of transplant
Population: All patients who received a transplant and engrafted. All patients were analyzed together since the definition for platelet engraftment is the same regardless of disease and only the time until overall platelet engraftment was the outcome of interest.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Multiple Myeloma | Time to Platelet Engraftment | 16.5 days |