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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients will undergo donor/recipient bone marrow | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| melphalan | Drug | melphalan (140 mg/m2 IV on day -7) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Patients Undergoing an Allo HCT Transplant Who Have a KIR Favorable Donor. | 1 year |
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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
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:
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| Name | Affiliation | Role |
|---|---|---|
| Brian Shaffer, MD | Memorial Sloan Kettering Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Memorial Sloan Kettering Cancer Center | New York | New York | 10065 | United States |
Not provided
| Label | URL |
|---|---|
| Memorial Sloan Kettering Cancer Center | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 21, 2020 |
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| fludarabine | Drug | fludarabine (40 mg/m2/d on days -5 through -2) |
|
|
| thiotepa | Drug | thiotepa (5 mg/kg IV on day -67) |
|
| Cyclophosphamide | Drug | cyclophosphamide (50 mg/kg IV on day +3 and +4) |
|
|
| Mesna | Drug |
|
|
| Mycophenolate Mofetil | Drug | (15 mg/kg PO/IV TID) |
|
|
| Filgrastim | Drug |
|
|
| Tacrolimus | Drug |
|
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Proportion of Patients Undergoing an Allo HCT Transplant Who Have a KIR Favorable Donor. | Posted | Count of Participants | Participants | 1 year |
|
|
|
1 year
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 | 17 | 44 | 10 | 44 | 43 | 44 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute kidney injury | Renal and urinary disorders | Systematic Assessment |
| ||
| Allergic reaction | Immune system disorders | Systematic Assessment |
| ||
| Back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Bronchial infection | Infections and infestations | Systematic Assessment |
| ||
| Delirium | Psychiatric disorders | Systematic Assessment |
| ||
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
| ||
| Encephalopathy | Nervous system disorders | Systematic Assessment |
| ||
| Hearing impaired | Ear and labyrinth disorders | Systematic Assessment |
| ||
| Hyponatremia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Ileus | Gastrointestinal disorders | Systematic Assessment |
| ||
| Infections and infestations - Other, specify | Infections and infestations | Systematic Assessment |
| ||
| Kidney infection | Infections and infestations | Systematic Assessment |
| ||
| Lower gastrointestinal hemorrhage | Gastrointestinal disorders | Systematic Assessment |
| ||
| Lung infection | Infections and infestations | Systematic Assessment |
| ||
| Myocardial infarction | Cardiac disorders | Systematic Assessment |
| ||
| Neutrophil count decreased | Investigations | Systematic Assessment |
| ||
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Sepsis | Infections and infestations | Systematic Assessment |
| ||
| Small intestine infection | Infections and infestations | Systematic Assessment |
| ||
| Tinnitus | Ear and labyrinth disorders | Systematic Assessment |
| ||
| Vestibular disorder | Ear and labyrinth disorders | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal Pain | Gastrointestinal disorders | Systematic Assessment |
| ||
| Activated partial thromboplastin time prolonged | Investigations | Systematic Assessment |
| ||
| Acute Kidney Injury | Renal and urinary disorders | Systematic Assessment |
| ||
| Alanine aminotransferase increased | Investigations | Systematic Assessment |
| ||
| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Anorexia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Aspartate aminotransferase increased | Investigations | Systematic Assessment |
| ||
| Blood bilirubin increased | Investigations | Systematic Assessment |
| ||
| Colitis | Gastrointestinal disorders | Systematic Assessment |
| ||
| Cystitis noninfective | Renal and urinary disorders | Systematic Assessment |
| ||
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
| ||
| Encephalopathy | Nervous system disorders | Systematic Assessment |
| ||
| Esophagitis | Gastrointestinal disorders | Systematic Assessment |
| ||
| Hypercalcemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hyperglycemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hyperkalemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hypermagnesemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hypertriglyceridemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hyperuricemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hypoalbuminemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hypocalcemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hypokalemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Lymphocyte count decreased | Investigations | Systematic Assessment |
| ||
| Nausea | Gastrointestinal disorders | Systematic Assessment |
| ||
| Neutrophil count decreased | Investigations | Systematic Assessment |
| ||
| Pain | General disorders | Systematic Assessment |
| ||
| Platelet count decreased | Investigations | Systematic Assessment |
| ||
| Pleural Effusion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Sepsis | Infections and infestations | Systematic Assessment |
| ||
| Vertigo | Ear and labyrinth disorders | Systematic Assessment |
| ||
| White blood cell decreased | Investigations | Systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Brian Shaffer, MD | Memorial Sloan Kettering Cancer Center | 646-608-3737 | shaffeb1@mskcc.org |
| Oct 22, 2024 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D019337 | Hematologic Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| D008558 | Melphalan |
| C024352 | fludarabine |
| C042382 | fludarabine phosphate |
| D013852 | Thiotepa |
| D003520 | Cyclophosphamide |
| D015080 | Mesna |
| D009173 | Mycophenolic Acid |
| D000069585 | Filgrastim |
| D016559 | Tacrolimus |
| ID | Term |
|---|---|
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D010649 | Phenylalanine |
| D024322 | Amino Acids, Aromatic |
| D000598 | Amino Acids, Cyclic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D013721 | Triethylenephosphoramide |
| D001388 | Aziridines |
| D001389 | Azirines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D010752 | Phosphoramide Mustards |
| D000476 | Alkanesulfonates |
| D017738 | Alkanesulfonic Acids |
| D000473 | Alkanes |
| D006839 | Hydrocarbons, Acyclic |
| D013438 | Sulfhydryl Compounds |
| D013457 | Sulfur Compounds |
| D013451 | Sulfonic Acids |
| D013456 | Sulfur Acids |
| D002208 | Caproates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D016179 | Granulocyte Colony-Stimulating Factor |
| D003115 | Colony-Stimulating Factors |
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D016298 | Hematopoietic Cell Growth Factors |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D011506 | Proteins |
| D001685 | Biological Factors |
| D018942 | Macrolides |
| D007783 | Lactones |
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| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|