Hematologic Malignancy
Conditions
Keywords
transplant conditioning, KIR/HLA based haploidentical donor selection, allogeneic hematopoietic cell transplantation
Brief summary
This study will test whether half matched donors with favorable KIR genes will reduce the risk of cancer recurring after transplant.
Interventions
DRUGmelphalan
melphalan (140 mg/m2 IV on day -7)
DRUGfludarabine
fludarabine (40 mg/m2/d on days -5 through -2)
DRUGthiotepa
thiotepa (5 mg/kg IV on day -67)
DRUGCyclophosphamide
cyclophosphamide (50 mg/kg IV on day +3 and +4)
DRUGMesna
DRUGMycophenolate Mofetil
(15 mg/kg PO/IV TID)
DRUGFilgrastim
DRUGTacrolimus
Sponsors
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Patients with any of the following hematologic malignancies who are considered to be eligible for allogeneic transplantation: * Acute lymphoid leukemia (ALL) in first complete remission (CR1) with high riskfor relapse including: * t(9;22) or detected BCR-ABL1 translocation by genomic methodologies * BCR-ABL1-Like B-ALL \[54\] including mutations of IKZF1 or CRLF2 * Translocations or mutations involving 11q23 (MLL) gene. * Hypodiploid karyotype * Deletion of 9p * Loss of 17p or TP53 mutation * T-lymphocyte lineage antigen expression (T-ALL) * CNS or other extramedullary involvement * WBC count \>/= 100,000 cells/μL at diagnosis * Relapsed ALL, biphenotypic/bilineal leukemia, or AML with \</= 10% blasts in the bone marrow prior to transplantation * Acute biphenotypic or bilineal leukemia in first or greater complete remission. * Acute myeloid leukemia (AML) in CR1 with intermediate or high risk features including: * Cytogeneic abnormalities associated with myelodysplatic syndrome including abnormalities of chromosome 5 or 7 * History of anti-neoplastic therapy (radiation or chemotherapy) * Extramedullary involvement * WBC count \>/= 100,00 cells/ul at diagnosis * Rearrangements or mutations of 11q23 (MLL) * Abnormalities of chromosome 3 * TP53 mutation or loss of 17p * Complex or monosomal karyotype * Normal karyotype with mutations of FLT3, RUNX1, or ASXL1 * Myleodysplastic syndrome, myeloproliferative neoplasms, or MDS/MPN overlap syndrome with: * International prognostic scoring system risk score of INT-2 or high risk at the time of transplant evaluation * Any risk category if life-threatening cytopenia exists * Karyotype or genomic changes that indicate high risk for progression to acute myelogenous leukemia, including abnormalities of chromosome 7 or 3, mutations of TP53, or complex or monosomal karyotype * Myelofibrosis with DIPSS scores of INT-2 or high risk or any risk category if life threatening cytopenias are present * Chronic myelomonocytic leukemia (CMML) * Chronic myeloid leukemia (CML) who have failed or are intolerant to BCR-ABL tyrosine kinase inhibitors * CML with BCR-ABL mutation consistent with poor response to tyrosine kinase inhibition (e.g. T351 l mutation) * CML with accelerated or blast phase with \<20% blasts after therapy * Hodgkin lymphoma: * Relapsed disease with progression after autologous bone marrow transplant or are ineligible for this procedure * Responding to therapy prior to enrollment * Non-Hodgkin lymphoma: * Responding to therapy prior to enrollment * Progression after autologous bone marrow transplant or are ineligible for this procedure * Chronic lymphocytic leukemia with high risk disease as defined by the EBMT consensus criteria * Patients aged 18 through 69 years old are eligible * Patients aged 70-75 with HCT-CI of 0-1 are eligible * High risk hematologic malignancies * Patients must have Karnofsky performance status \>/= 70% * Cardiac left ventricular ejection fraction \>/= 50% at rest * Total bilirubin \</= 2 mg/dL, except for patients with Gilbert's syndrome * AST and ALT \</= 5x ULN unless thought to be disease related * Estimated or measured creatinine clearance \> 50 mL/min * Hemoglobin adjusted pulmonary DLCO \>/= 50% of predicted, if Hgb is within normal range, unadjusted DLCO must be \>/= 50%
Exclusion criteria
* Persons with a HLA matched sibling donor. * Female patients who are pregnant or breast-feeding * Persons with an infection that is not responding to antimicrobial therapy * Persons who are seropositive for HIV. * Persons with uncontrolled central nervous system malignancy •Persons who do not meet the age and organ function criteria specified above Presence of psychiatric or neurologic disease, or lack of social support that limits the patient's ability to comply with the treatment protocol including supportive care, follow-up, and research tests. * Prior diagnosis of non-hematologic malignancy within 5 years of planned protocol therapy EXCEPT: * Diagnosis of breast ductal carcinoma in situ treated with curative intent * Diagnosis of prostate adenocarcinoma with Gleasons score \</= 6 treated with curative intent * Non-melanomatous skin cancer
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of Patients Undergoing an Allo HCT Transplant Who Have a KIR Favorable Donor. | 1 year |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Patients Will Undergo Donor/Recipient Bone Marrow All patients will undergo haploidentical, allogeneic hematopoietic cell transplantation. Conditioning will consist of fludarabine, melphalan, and thiotepa. Graft versus host disease prophylaxis will be with post-transplant cyclophosphamide in addition to standard tacrolimus and mycophenolate mofetil. Donors will undergo HLA and KIR geno- and allotyping to determine the best donor.
melphalan: melphalan (140 mg/m2 IV on day -7)
fludarabine: fludarabine (40 mg/m2/d on days -5 through -2)
thiotepa: thiotepa (5 mg/kg IV on day -67)
Cyclophosphamide: cyclophosphamide (50 mg/kg IV on day +3 and +4)
Mesna
Mycophenolate Mofetil: (15 mg/kg PO/IV TID)
Filgrastim
Tacrolimus | 44 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Inevaluable | 5 |
Baseline characteristics
| Characteristic | Patients Will Undergo Donor/Recipient Bone Marrow |
|---|---|
| Age, Continuous | 62 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 9 Participants |
| Race (NIH/OMB) Black or African American | 7 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 | 3 Participants |
| Race (NIH/OMB) White | 25 Participants |
| Region of Enrollment United States | 44 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 17 / 44 |
| other Total, other adverse events | 43 / 44 |
| serious Total, serious adverse events | 10 / 44 |
Outcome results
Primary
Proportion of Patients Undergoing an Allo HCT Transplant Who Have a KIR Favorable Donor.
Time frame: 1 year
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Patients Will Undergo Donor/Recipient Bone Marrow | Proportion of Patients Undergoing an Allo HCT Transplant Who Have a KIR Favorable Donor. | Pts without KIR favorable donor | 21 Participants |
| Patients Will Undergo Donor/Recipient Bone Marrow | Proportion of Patients Undergoing an Allo HCT Transplant Who Have a KIR Favorable Donor. | Pts with KIR favorable donor | 23 Participants |