Malignant Neoplasm
Conditions
Brief summary
This phase II trial studies how well haploidentical donor hematopoietic stem cell transplant works in treating patients with hematologic malignancies. Giving chemotherapy and total-body irradiation before a donor stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. Giving an infusion of the donor's T cells (donor lymphocyte infusion) may replace the patient's immune cells and help destroy any remaining cancer cells. When the stem cells from a related donor, that closely matches the patient's blood, are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.
Detailed description
PRIMARY OBJECTIVES: I. Examine the 1 year disease free survival (DFS) rate of patients with maternal donors or sibling donors who share the maternal haplotype (maternal group) and compare them to patients receiving cells from donors who have points from other characteristics such as killer immunoglobulin-like receptor (KIR) ligand mismatching, minor histocompatibility antigen (MHag) differences, or number of human leukocyte antigen (HLA) mismatches (non-maternal group). SECONDARY OBJECTIVES: I. Assess the incidences of relapse and graft-versus-host disease (GVHD) in maternal recipients whose only eligible donors are offspring. II. Assess the incidence of grades III-IV GVHD in female recipients with male donors. III. Compare the rates of DFS in recipient-donor combinations in which there is at least 1 KIR ligand mismatch versus those without a KIR ligand mismatch. OUTLINE: Patients undergo total body irradiation (TBI) twice daily (BID) on days -9 to -6, undergo donor lymphocyte infusion (DLI) on day -6, and receive cyclophosphamide intravenously (IV) over 2 hours on days -3 and -2. TRANSPLANT: Patients undergo haploidentical allogeneic hematopoietic stem cell transplant on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV beginning on day -1 with taper beginning on day 42, and mycophenolate mofetil IV BID from day -1 to day 28. After completion of study treatment, patients are followed up at 90, 180, and 270 days, and 1 year.
Interventions
RADIATIONTotal-body irradiation
Undergo TBI
BIOLOGICALDonor lymphocytes infusion (DLI)
Undergo DLI
DRUGCyclophosphamide
Given IV
Undergo haploidentical allogeneic HSCT
DRUGTacrolimus
Given IV
DRUGMycophenolate mofetil
Given IV
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 without morphological evidence of disease in which allogeneic HSCT is thought to be beneficial. 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 must have adequate organ function: 1. LVEF (Left ventricular ejection fraction) of \>50% 2. Diffusion Capacity for Carbon Monoxide (DLCO) \>50% of predicted corrected for hemoglobin 3. Adequate liver function as defined by a serum bilirubin \<1.8, Aspartate Aminotransferase (AST) or alanine aminotransferase (ALT) \< 2.5X upper limit of normal 4. Creatinine clearance of \> 60 ml/min 4. Performance status \> 80% (TJU Karnofsky) 5. Hematopoietic Comorbidity Index (HCT-CI) Score \< 5 Points 6. Patients must be willing to use contraception if they have childbearing potential 7. Able to give informed consent, or if decisionally impaired, have a legal next of kin or guardian that can give informed consent
Exclusion criteria
1. Performance status \< 80 % (TJU Karnofsky) 2. HCT-CI Score \> 5 Points 3. Combination of Performance status of \< 80% (TJU Karnofsky) and an HCT-CI of 4 points or more. 4. HIV positive 5. Active involvement of the central nervous system with malignancy 6. Psychiatric disorder that would preclude patients from signing an informed consent 7. Pregnancy 8. Patients with life expectancy of \< 6 months for reasons other than their underlying hematologic/oncologic disorder 9. Patients who have received alemtuzumab within 8 weeks of the transplant admission, or who have recently received horse or rabbit anti-thymocyte globulin and have an ATG level of \> 2 ugm/ml 10. Patients who cannot receive cyclophosphamide 11. 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 |
|---|---|---|
| Number of Participants With Disease-free Survival (DFS) | 1 year | Disease free survival (DFS), defined as the time to death, relapse or disease progression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Relapse of Disease | Up to 1 year | Relapse of Disease is defined as the return of a disease or the signs and symptoms of a disease after a period of improvement. Relapse is almost always associated with the immunological failure of the donor immune system to recognize and/or respond to reemergence of a tumor. The number of participants with relapse of disease will be collected. |
| Rate of Grade III-IV GVHD in Female Recipients With Male Donors | Up to 1 year | The rates of grade III-IV GVHD in female recipients with male donors will be computed with corresponding exact binomial 95% confidence intervals. |
| The Rates of Grade III-IV GVHD in Female Recipients With Male Donors Will be Computed With Corresponding Exact Binomial 95% Confidence Intervals. | Up to 1 year | The difference in DFS in recipient-donor combinations in which there is at least 1 KIR ligand mismatch versus those without a KIR ligand mismatch will be tested using log-rank test. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Haploidentical Allogeneic HSCT) Patients undergo TBI BID on days -9 to -6, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2.
TRANSPLANT: Patients undergo haploidentical allogeneic hematopoietic stem cell transplant on day 0.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV beginning on day -1 with taper beginning on day 42, and mycophenolate mofetil IV BID from day -1 to day 28.
Total-body irradiation: Undergo TBI
Donor lymphocytes infusion (DLI): Undergo DLI
Cyclophosphamide: Given IV
Allogeneic hematopoietic stem cell transplantation (HSCT): Undergo haploidentical allogeneic HSCT
Tacrolimus: Given IV
Mycophenolate mofetil: Given IV | 4 |
| Total | 4 |
Baseline characteristics
| Characteristic | Treatment (Haploidentical Allogeneic HSCT) |
|---|---|
| Age, Continuous | 55 years STANDARD_DEVIATION 11.35 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 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 | 1 Participants |
| Region of Enrollment United States | 4 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 4 |
| other Total, other adverse events | 4 / 4 |
| serious Total, serious adverse events | 4 / 4 |
Outcome results
Primary
Number of Participants With Disease-free Survival (DFS)
Disease free survival (DFS), defined as the time to death, relapse or disease progression.
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Haploidentical Allogeneic HSCT) | Number of Participants With Disease-free Survival (DFS) | 1 Participants |
Secondary
Number of Participants With Relapse of Disease
Relapse of Disease is defined as the return of a disease or the signs and symptoms of a disease after a period of improvement. Relapse is almost always associated with the immunological failure of the donor immune system to recognize and/or respond to reemergence of a tumor. The number of participants with relapse of disease will be collected.
Time frame: Up to 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Haploidentical Allogeneic HSCT) | Number of Participants With Relapse of Disease | 2 Participants |
Secondary
Rate of Grade III-IV GVHD in Female Recipients With Male Donors
The rates of grade III-IV GVHD in female recipients with male donors will be computed with corresponding exact binomial 95% confidence intervals.
Time frame: Up to 1 year
Population: No data were collected or analyzed.
Secondary
The Rates of Grade III-IV GVHD in Female Recipients With Male Donors Will be Computed With Corresponding Exact Binomial 95% Confidence Intervals.
The difference in DFS in recipient-donor combinations in which there is at least 1 KIR ligand mismatch versus those without a KIR ligand mismatch will be tested using log-rank test.
Time frame: Up to 1 year
Population: No data were collected or analyzed.