Haploidentical (Half-matched) Related Donor Stem Cell Transplantation Using Killer Immunoglobulin-like Receptors in Addition to Normal Selection Factors to Determine the Best Donor

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02880293

Collaborator

(none)

Enrollment

Location

Arm

83.3

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will test whether half matched donors with favorable KIR genes will reduce the risk of cancer recurring after transplant.

Condition or Disease	Intervention/Treatment	Phase
Hematologic Malignancy	Drug: melphalan Drug: fludarabine Drug: thiotepa Drug: Cyclophosphamide Drug: Mesna Drug: Mycophenolate Mofetil Drug: Filgrastim Drug: Tacrolimus	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

44 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Partially HLA-Mismatched Related Donor Hematopoietic Stem Cell Transplantation Using Killer Immunoglobulin Receptor and Human Leukocyte Antigen Based Donor Selection

Study Start Date :

Aug 23, 2016

Anticipated Primary Completion Date :

Aug 1, 2023

Anticipated Study Completion Date :

Aug 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: melphalan melphalan (140 mg/m2 IV on day -7) Other Names: Alkeran® Drug: fludarabine fludarabine (40 mg/m2/d on days -5 through -2) Other Names: FLUDARA® Drug: thiotepa thiotepa (5 mg/kg IV on day -67) Drug: Cyclophosphamide cyclophosphamide (50 mg/kg IV on day +3 and +4) Other Names: Cytoxan® Drug: Mesna Other Names: Mesnex® Drug: Mycophenolate Mofetil (15 mg/kg PO/IV TID) Other Names: CellCept® Drug: Filgrastim Other Names: Neupogen® Drug: Tacrolimus Other Names: Prograf®

Arm

Intervention/Treatment

Experimental: 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.

Drug: melphalan

melphalan (140 mg/m2 IV on day -7)

Other Names:

Alkeran®

Drug: fludarabine

fludarabine (40 mg/m2/d on days -5 through -2)

Other Names:

FLUDARA®

Drug: thiotepa

thiotepa (5 mg/kg IV on day -67)

Drug: Cyclophosphamide

cyclophosphamide (50 mg/kg IV on day +3 and +4)

Other Names:

Cytoxan®

Drug: Mesna

Other Names:

Mesnex®

Drug: Mycophenolate Mofetil

(15 mg/kg PO/IV TID)

Other Names:

CellCept®

Drug: Filgrastim

Other Names:

Neupogen®

Drug: Tacrolimus

Other Names:

Prograf®

Outcome Measures

Primary Outcome Measures

proportion of patients undergoing an allo HCT transplant who have a KIR favorable donor. [1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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