Hematological Malignancies
Conditions
Keywords
Reduced Intensity Haploidentical Transplant
Brief summary
Many patients with hematological malignancies (leukemia, lymphoma, multiple myeloma) cannot undergo hematopoietic stem cell transplantation (HSCT) because they do not have a well matched donor. HSCT from partially matched family donors (haploidentical HSCT) is an option for most patients but has been associated with poor outcomes. This study was designed to test whether using an exact amount of a donor's lymphocytes (white cells) and dividing the transplant process into 2 steps, would increase overall survival by decreasing complications. The therapy is reduced intensity so it is targeted, but not limited to, patients over the age of 65 or those who have had previous transplants.
Detailed description
Haploidentical hematopoietic stem cell transplant is a life saving therapy for patients who are without well matched donors. This type of therapy has been associated with poor outcomes in the past due to complications such as infection. The Jefferson 2 Step approach was designed to allow the infusion of an exact dose of tolerized lymphocytes in haploidentical transplant in order to allow for immune reconstitution post transplant to avoid infectious complications while still having acceptable rates of GVHD. In this approach, older patients or patients who were transplanted previously with high-risk hematological malignancies undergo chemotherapy with fludarabine and cytarabine or thiotepa. The patients then receive an exact dose of their donors' lymphocytes. The phase I portion of the study determined the optimal dose of lymphocytes. Two days after receiving the donor lymphocytes, the patients receive 2 daily doses of cyclophosphamide. The purpose of the cyclophosphamide is for in-vivo tolerization of the lymphocytes. One day after receiving cyclophosphamide, the patients receive stem cell from their donor. Tacrolimus and mycophenolate mofetil are used as GVHD prophylaxis.
Interventions
DEVICEHaploidentical Allogeneic Transplantation
Patients undergoing reduced intensity haploidentical hematopoietic stem cell transplant from a partially matched related donor.
Sponsors
Sidney Kimmel Cancer Center at Thomas Jefferson University
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
1. Any patient with a hematologic or oncologic diagnosis in which allogeneic HSCT is thought to be beneficial, and in whom front-line therapy has already been applied. 2. Patients must have a related donor who is a two or more allele mismatch at the HLA-A;B; C; DR loci. 3. Patients who have sibling donors with a one antigen mismatch due to recombination will not be enrolled in this protocol. 4. Patients must adequate organ function: 1. LVEF of \>45% 2. DLCO \>45% of predicted corrected for hemoglobin 3. Adequate liver function as defined by a serum bilirubin \<1.8, AST or ALT \< 2.5X upper limit of normal 4. Serum creatinine \< 2.0 mg/dl or creatinine clearance of \> 40 ml/min 5. Performance status \> 70% (Karnofsky) 6. Patients must be willing to use contraception if they have childbearing potential 7. Able to give informed consent
Exclusion criteria
1. Performance status of \< 70% (Karnofsky) 2. HIV positive 3. Active involvement of the central nervous system with malignancy 4. Psychiatric disorder that would preclude patients from signing an informed consent 5. Pregnancy 6. Patients with life expectancy of \< 6 months for reasons other than their underlying hematologic/oncologic disorder or complications there from. 7. Patients who have received alemtuzumab within 8 weeks of transplant admission, or who have recently received horse or rabbit anti-thymocyte globulin and have ATG levels of \> 2 µgm/ml. 8. Patients who cannot receive cyclophosphamide 9. Patients with evidence of another malignancy, exclusive of a skin cancer that requires only local treatment, should not be enrolled on this protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival at 6 Months Post-transplant in Patients Receiving a Partially-matched Related Donor Allogeneic Transplant After Reduced-intensity Conditioning | 6 months | Number of patients alive at 6 months post-transplant |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants With Successful Engraftment | 6 months |
| Immune Reconstitution | Up to 5 years |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Transplantation | 34 |
| Total | 34 |
Baseline characteristics
| Characteristic | Transplantation |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 20 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants |
| Age, Continuous | 59.23 years STANDARD_DEVIATION 15.57 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 33 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 27 Participants |
| Region of Enrollment United States | 34 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 34 |
| serious Total, serious adverse events | 14 / 34 |
Outcome results
Primary
Overall Survival at 6 Months Post-transplant in Patients Receiving a Partially-matched Related Donor Allogeneic Transplant After Reduced-intensity Conditioning
Number of patients alive at 6 months post-transplant
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Transplantation | Overall Survival at 6 Months Post-transplant in Patients Receiving a Partially-matched Related Donor Allogeneic Transplant After Reduced-intensity Conditioning | 22 Participants |
Secondary
Immune Reconstitution
Time frame: Up to 5 years
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Transplantation | Immune Reconstitution | CD3/8 count at day 28 | 26.50 cells/ul |
| Transplantation | Immune Reconstitution | CD3/8 count at day 90 | 119.2 cells/ul |
| Transplantation | Immune Reconstitution | CD3/4 count at day 28 | 35.945 cells/ul |
| Transplantation | Immune Reconstitution | CD3/4 count at day 90 | 104.540 cells/ul |
Secondary
Number of Participants With Successful Engraftment
Time frame: 6 months
Population: 32 patients are evaluable for engraftment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Transplantation | Number of Participants With Successful Engraftment | 31 Participants |