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

Memorial Sloan Kettering Cancer Center (MSK)

Status

Completed

Conditions

Hematologic Malignancy

Treatments

Drug: Mycophenolate Mofetil

Drug: melphalan

Drug: Cyclophosphamide

Drug: Filgrastim

Drug: Tacrolimus

Drug: thiotepa

Drug: fludarabine

Drug: Mesna

Study type

Interventional

Funder types

Other

Identifiers

NCT02880293

16-1237

Details and patient eligibility

About

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

Enrollment

44 patients

Sex

All

Ages

18 to 75 years old

Volunteers

No 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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

44 participants in 1 patient group

Patients will undergo donor/recipient bone marrow

Experimental group

Description:

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.

Treatment: