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

NCT ID: NCT02880293

Last Updated: 2024-12-06

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

44 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-08-23

Study Completion Date

2023-11-20

Brief Summary

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

Detailed Description

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Conditions

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Hematologic Malignancy

Keywords

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transplant conditioning KIR/HLA based haploidentical donor selection allogeneic hematopoietic cell transplantation

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

melphalan

Intervention Type DRUG

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

fludarabine

Intervention Type DRUG

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

thiotepa

Intervention Type DRUG

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

Cyclophosphamide

Intervention Type DRUG

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

Mesna

Intervention Type DRUG

Mycophenolate Mofetil

Intervention Type DRUG

(15 mg/kg PO/IV TID)

Filgrastim

Intervention Type DRUG

Tacrolimus

Intervention Type DRUG

Interventions

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melphalan

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

Intervention Type DRUG

fludarabine

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

Intervention Type DRUG

thiotepa

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

Intervention Type DRUG

Cyclophosphamide

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

Intervention Type DRUG

Mesna

Intervention Type DRUG

Mycophenolate Mofetil

(15 mg/kg PO/IV TID)

Intervention Type DRUG

Filgrastim

Intervention Type DRUG

Tacrolimus

Intervention Type DRUG

Other Intervention Names

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Alkeran® FLUDARA® Cytoxan® Mesnex® CellCept® Neupogen® Prograf®

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Brian Shaffer, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

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Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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https://www.mskcc.org/

Memorial Sloan Kettering Cancer Center

Other Identifiers

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16-1237

Identifier Type: -

Identifier Source: org_study_id