Multiple Myeloma
Conditions
Brief summary
The primary goal of this study is to determine the feasibility and safety of giving two doses of denileukin diftitox (DD) at days 0 and 21 post autologous stem cell transplantation in a dose escalation fashion. Secondary goals include evaluating the the effect of DD on the number and percentage of T-regs in the peripheral blood post transplant at each dose level, the effect of DD on T cell (CD4/CD8) reconstitution post transplant at each dose level and determining the time to engraftment: absolute neutrophil count (\>0.5 x 10\^9/L for 3 consecutive days), and platelet (\>20X 10\^9/L for 3 consecutive days). The hypothesis for the study is based on the ability of DD to deplete T-regs and subsequently enhance the immune reconstitution and reverse post transplant lymphopenia. This may indirectly enhance the efficacy of autologous transplantation and reduce disease relapse.
Interventions
After receiving their stem cell transplant on Day 0, participants will receive study agent via a 30 minute infusion. Participants will also receive a 30 minute infusion of study agent on Day 21. Follow-up visits for clinical assessment, blood draws for routine clinical laboratory studies and for immuno-correlative studies will also take place on days 42, 90, 180 and 360.
Sponsors
Eisai Inc.
Barbara Ann Karmanos Cancer Institute
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
All patients age \> =18 who have been diagnosed with Multiple Myeloma and are scheduled for autologous peripheral blood hematopoietic stem cell transplant (AHSCT) will be screened for eligibility. Patients must fulfill all of the following inclusion criteria to be eligible for this study: 1. Diagnosis of Multiple Myeloma 2. Age \>=18 and no more than 70 years. 3. Able to understand and sign a consent form. 4. Can collect peripheral blood stem cells with a CD34+ cell dose of at least 5.0 x 106/kg. The CD34 molecule is a Cluster of Differentiation molecule present on hematopoietic stem cells. 5. Conditioning regimen to be high dose Melphalan at a dose of 200mg/m2. 6. Karnofsky Performance Score (KPS) \>60 or ECOG (Eastern Cooperative Oncology Group) performance status \<=2 7. Kidney function:Creatinine \<2.0 mg/dl or creatinine clearance \>50 ml/min 8. Heart function: Ejection fraction \>45% 9. Liver function tests :Serum bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) less than 3 X upper limit of normal 10. Lung function tests: Forced Vital Capacity (FVC), Forced Expiratory Volume in One Second (FEV1) or Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) \>45% predicted
Exclusion criteria
1. Age \<18 years or \> 70 years 2. Previous exposure to denileukin diftitox. 3. Patients with documented uncontrolled central nervous system (CNS) disease. 4. Previous AHSCT. 5. Significant organ dysfunction deemed to be inappropriate for autologous transplantation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assess Toxicities of Giving Two Doses of Ontak at Days 0 and 21 Post Autologous Stem Cell Transplantation in a Dose Escalation Fashion. | Up to 21 days post transplant | After drug infusion, participants will be closely monitored for at least 4 hours for side effects |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Evaluate the Effect of Ontak on the Number and Percentage of Regulatory T Cells in the Peripheral Blood Post Transplant at Each Dose Level. | days 0 and 21 post autologous stem cell transplantation | — |
| To Evaluate the Effect of Ontak on T Cell CD4/CD8 Reconstitution Post Transplant at Each Dose. | days 0 and 21 post autologous stem cell transplantation | — |
| To Evaluate the Effect of Ontak on Engraftment of Neutrophils and Platelets Post Transplant at Each Dose. | days 0 and 21 post autologous stem cell transplantation | During hospitalization stay (approximately 2 weeks), participants will receive injections of G-CSF on a daily basis starting on Day 6 and ending when white blood cells have engrafted. Participants usually remain hospitalized until engraftment. |
Countries
United States
Participant flow
Recruitment details
Cancer center clinic.
Participants by arm
| Arm | Count |
|---|---|
| Denileukin Diftitox (Ontak) Denileukin Diftitox (Ontak) administered Post Autologous Transplantation.
Denileukin Diftitox (Ontak) : After receiving their stem cell transplant on Day 0, participants will receive study agent via a 30 minute infusion. Participants will also receive a 30 minute infusion of study agent on Day 21.
Follow-up visits for clinical assessment, blood draws for routine clinical laboratory studies and for immuno-correlative studies will also take place on days 42, 90, 180 and 360. | 2 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Denileukin Diftitox (Ontak) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Age, Continuous | 58 years STANDARD_DEVIATION 10 |
| Region of Enrollment United States | 2 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 2 |
| serious Total, serious adverse events | 2 / 2 |
Outcome results
Primary
Assess Toxicities of Giving Two Doses of Ontak at Days 0 and 21 Post Autologous Stem Cell Transplantation in a Dose Escalation Fashion.
After drug infusion, participants will be closely monitored for at least 4 hours for side effects
Time frame: Up to 21 days post transplant
Secondary
To Evaluate the Effect of Ontak on Engraftment of Neutrophils and Platelets Post Transplant at Each Dose.
During hospitalization stay (approximately 2 weeks), participants will receive injections of G-CSF on a daily basis starting on Day 6 and ending when white blood cells have engrafted. Participants usually remain hospitalized until engraftment.
Time frame: days 0 and 21 post autologous stem cell transplantation
Secondary
To Evaluate the Effect of Ontak on T Cell CD4/CD8 Reconstitution Post Transplant at Each Dose.
Time frame: days 0 and 21 post autologous stem cell transplantation
Secondary
To Evaluate the Effect of Ontak on the Number and Percentage of Regulatory T Cells in the Peripheral Blood Post Transplant at Each Dose Level.
Time frame: days 0 and 21 post autologous stem cell transplantation