Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02880293
Recruitment Status : Recruiting
First Posted : August 26, 2016
Last Update Posted : January 27, 2020
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

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 Not Applicable

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 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 : August 23, 2016
Estimated Primary Completion Date : August 2021
Estimated Study Completion Date : August 2021

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 Name: Alkeran®

Drug: fludarabine
fludarabine (40 mg/m2/d on days -5 through -2)
Other Name: FLUDARA®

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

Drug: Cyclophosphamide
cyclophosphamide (50 mg/kg IV on day +3 and +4)
Other Name: Cytoxan®

Drug: Mesna
Other Name: Mesnex®

Drug: Mycophenolate Mofetil
(15 mg/kg PO/IV TID)
Other Name: CellCept®

Drug: Filgrastim
Other Name: Neupogen®

Drug: Tacrolimus
Other Name: Prograf®




Primary Outcome Measures :
  1. proportion of patients undergoing an allo HCT transplant who have a KIR favorable donor. [ Time Frame: 1 year ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02880293


Contacts
Layout table for location contacts
Contact: Brian Shaffer, MD 212-639-2212

Locations
Layout table for location information
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Brian Shaffer, MD    212-639-2212      
Principal Investigator: Brian Shaffer, MD         
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Investigators
Layout table for investigator information
Principal Investigator: Brian Shaffer, MD Memorial Sloan Kettering Cancer Center
Additional Information:
Layout table for additonal information
Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT02880293    
Other Study ID Numbers: 16-1237
First Posted: August 26, 2016    Key Record Dates
Last Update Posted: January 27, 2020
Last Verified: January 2020
Keywords provided by Memorial Sloan Kettering Cancer Center:
transplant conditioning
KIR/HLA based haploidentical donor selection
allogeneic hematopoietic cell transplantation
Additional relevant MeSH terms:
Layout table for MeSH terms
Hematologic Neoplasms
Neoplasms
Neoplasms by Site
Hematologic Diseases
Mycophenolic Acid
Cyclophosphamide
Melphalan
Thiotepa
Fludarabine
Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Calcineurin Inhibitors
Enzyme Inhibitors
Antibiotics, Antineoplastic
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents