CLL / SLL, Mantle Cell Lymphoma, Multiple Myeloma, Non Hodgkin's Lymphoma, Waldenstroms
Conditions
Keywords
Low Grade B Cell Malignancies, nonmyeloablative transplant, allogeneic
Brief summary
A non-myeloablative treatment strategy and uniform selection criteria will enable patients with a variety of low grade B-Cell malignancies to attain long term disease control without unacceptably high treatment related mortality.
Detailed description
Non myeloablative transplant aims to achieve the immunological advantage of graft versus tumor effect as conventional myeloablative therapy without causing high treatment related toxicities. Non myeloablative transplant has been gaining wider acceptance as a way to achieve longer disease free and over all survival in patients with low grade B-cell malignancies, which otherwise is an incurable disease. Recent studies of non-myeloablative HSCT have demonstrated the powerful effect of graft versus leukemia alone against myeloma and other malignant B-cell malignancies if the transplant is performed for low grade, low volume disease.
Interventions
DRUGFludarabine
Fludarabine 30 mg/m2/day x 3 days
RADIATIONTotal Body Irradiation
TBI 200cGy x1 dose on transplant day
OTHERInfusion of Stem Cells
On Day 0 pts will received an infusion of HLA matched sibling donor stem cells. Dose is determined by the volume of cells obtained from donor. Minimum dose is 2x10\*6 CD34+ cells per kilogram of recipient weight.
Sponsors
University of Alabama at Birmingham
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Stage II or III non-progressive disease Multiple Myeloma. * CLL/SLL, and low grade Hodgkin Lymphomas that are in a very good partial response or complete response with non-progressive disease. * ≤ 70 years old. * Eligible and willing HLA matched related donor. * Bilirubin \<2xULN. * ALT and AST \<3xULN. * LVEF \> 40%. * Creatinine Clearance \>40mL/min. * Pulmonary function DLCO corrected to ≥ 70%. * Minimum performance score of 70%. * Platelet count \>130 x103 micro L. * LDH ≤1.5xULN. * No proceeding co-morbid condition that significantly increases the risk of severe regimen related toxicity. * No uncontrolled infections.
Exclusion criteria
* Age \>70 years old. * Performance status \<70%. * Uncontrolled infections or is HIV positive * Prior malignancies that are felt to have a \<80% probability of being cured. * Pregnant, breastfeeding, or refuse to use contraceptive techniques during and for 12 months following transplant. * Prior Allograft * History of rapidly growing disease at diagnosis or at any progression or have MDS. * No eligible and willing HLA matched donor.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progressive Free Survival Post Transplant | 100 days post transplant | subjects surviving without disease progression at 100 days after transplant as evidenced by decreased disease and no new disease showing on radiologic scans and / or bone marrow pathology. |
| Progression Free Survival Post Transplant | 2 years post transplant | Subjects surviving without disease progression 2 years after transplant as evidenced by no new disease showing on radiologic scans and / or bone marrow pathology. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Non-relapse Treatment Related Mortality | Within 100 days post transplant | Death related to treatment without relapse within 100 days after transplant |
| Number of Participants With Detectable Donor Chimerism at up to 100 Days Post Transplant | Post transplant up to 100 days post transplant | Measured by number of participants that have chimerism study results that show the number of donor cells and the number of recipient cells present in the blood after post-transplant lymphocyte infusions continue to be predominately either donor or recipient. |
| Composite Incidence of Acute and Chronic Graft Versus Host Disease | Up to 100 days post transplant. | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Single Arm Trial Single Arm Intervention trial as noted in interventions section
Fludarabine: Fludarabine 30 mg/m2/day x 3 days
Total Body Irradiation: TBI 200cGy x1 dose on transplant day
Infusion of Stem Cells: On Day 0 pts will received an infusion of HLA matched sibling donor stem cells. Dose is determined by the volume of cells obtained from donor. Minimum dose is 2x10\*6 CD34+ cells per kilogram of recipient weight. | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 2 |
Baseline characteristics
| Characteristic | Single Arm Trial |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 5 |
| serious Total, serious adverse events | 3 / 5 |
Outcome results
Primary
Progression Free Survival Post Transplant
Subjects surviving without disease progression 2 years after transplant as evidenced by no new disease showing on radiologic scans and / or bone marrow pathology.
Time frame: 2 years post transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Single Arm Trial | Progression Free Survival Post Transplant | 2 participants |
Primary
Progressive Free Survival Post Transplant
Subjects surviving without disease progression 365 days after transplant as evidenced by decreased disease and no new disease showing on radiologic scans and / or bone marrow pathology.
Time frame: 365 days post transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Single Arm Trial | Progressive Free Survival Post Transplant | 4 participants |
Primary
Progressive Free Survival Post Transplant
subjects surviving without disease progression at 100 days after transplant as evidenced by decreased disease and no new disease showing on radiologic scans and / or bone marrow pathology.
Time frame: 100 days post transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Single Arm Trial | Progressive Free Survival Post Transplant | 4 participants |
Primary
Progressive Free Survival Post Transplant
Subjects surviving without disease progression 180 days after transplant as evidenced by decreased disease and no new disease showing on radiologic scans and / or bone marrow pathology.
Time frame: 180 days post transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Single Arm Trial | Progressive Free Survival Post Transplant | 4 participants |
Secondary
Composite Incidence of Acute and Chronic Graft Versus Host Disease
Time frame: Up to 100 days post transplant.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Single Arm Trial | Composite Incidence of Acute and Chronic Graft Versus Host Disease | 2 participants |
Secondary
Non-relapse Treatment Related Mortality
Death related to treatment without relapse within 100 days after transplant
Time frame: Within 100 days post transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Single Arm Trial | Non-relapse Treatment Related Mortality | 0 participants |
Secondary
Number of Participants With Detectable Donor Chimerism at up to 100 Days Post Transplant
Measured by number of participants that have chimerism study results that show the number of donor cells and the number of recipient cells present in the blood after post-transplant lymphocyte infusions continue to be predominately either donor or recipient.
Time frame: Post transplant up to 100 days post transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Single Arm Trial | Number of Participants With Detectable Donor Chimerism at up to 100 Days Post Transplant | 1 participant |