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| Name | Class |
|---|---|
| Boston Children's Hospital | OTHER |
| Children's Hospital Medical Center, Cincinnati | OTHER |
| Children's Hospital and Health System Foundation, Wisconsin | OTHER |
This is a genetic disease (transmitted through the parents' genes) called Fanconi Anemia. Because of that genetic disease, the bone marrow has changed and now has failed, or has given rise to a preleukemia called myelodysplastic syndrome (MDS) or leukemia (acute myelogenous leukemia or AML).
Without treatment these complications of Fanconia anemia (FA) are fatal. The only treatment that can cure these complications is an allogeneic transplant of stem cells, meaning, giving the patient bone marrow cells from a healthy donor that can produce normal blood cells that will replace the bone marrow that is sick.
What has been given for the treatment of FA in the past is to use a combination of low doses of radiation to the whole body (total body irradiation) and low doses of the chemotherapy drugs (cyclophosphamide and fludarabine) before the transplant. However, the use of radiation can, later on, increase the chances of getting a second cancer of the skin, head or the neck. These chances of a second cancer are higher than normal in patients with FA.
The purpose of this study is to find out if the doctors can do the same thing with the same chemotherapy drugs used in the past. However physicians will use another chemotherapy drug called busulfan instead of the radiation. The goal of this study is to get rid of the short term and long term risks of the radiation. The first new part of this treatment will be to replace drugs for radiation with chemotherapy drugs.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| chemotherapy-based cytoreductive regimen plus a CD34+ selected | Experimental | This phase II trial is designed to investigate the safety and efficacy of a chemotherapy-based cytoreductive regimen plus a CD34+ selected T-cell depleted peripheral blood stem cell (PBSC) stem cell transplant for the treatment of patients with Fanconi anemia and severe hematologic disease. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Busulfan, fludarabine, & cyclophosphamide with immunosuppression with ATG and cyclosporine. | Drug | There are three parts in this transplant study. 1) There will be a pre-transplant - preparation - period to see if patient qualifies for the transplant study. This will be done as an outpatient and lasts 2-4 weeks. Once this is completed, there will be 2) the transplant period itself, during which the patient will be admitted and will be an inpatient. This period usually last for 4-6 weeks. Following that, there will be a 3) post transplant period, during which the patient will be watched carefully and monitored in clinic as an out patient. The post transplant period lasts from three months to one year. |
| Measure | Description | Time Frame |
|---|---|---|
| Successful Neutrophil Engraftment | 2 years | |
| The Incidence of Early Transplant Related Mortality | 2 years | |
| The Incidence of Acute GvHD | 100 days | |
| The Incidence of Chronic GvHD | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival at 3 Years | Overall Survival is defined as time from date of transplant to event (death from any cause) or last follow-up. | 3 years |
| Disease-free Survival at 3 Years | Defined as time from date of transplant to relapse, graft rejection or graft failure, or death. Primary non-engraftment is diagnosed when the participants fails to achieve an ANC >/= 500/ul at any time in the first 28 days post-transplant. For participants with MDS or AML, relapse will be analyzed as to type and genetic origin of the MDS/leukemic cells. These will be defined by an increasing number of blasts in the marrow over 5% by the presence of circulating peripheral blasts, or by the presence of blasts in any extramedullary site. Cytogenetic analysis of the marrow and/or peripheral blood will also be obtained for the diagnosis of relapse. |
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Inclusion Criteria:
Patients must have a diagnosis of Fanconi anemia (confirmed by mitomycin C or diepoxybutane [DEB] chromosomal breakage testing at an approved laboratory).
Hematologic Diagnosis and Status - Patients must have one of the following hematologic diagnoses:
AND at least one of the following features:
Platelet count <20 x 109/L or platelet transfusion dependence*
ANC <1000 x 109/L
Hgb <8 gm/dl or red cell transfusion dependence*
Myelodysplastic Syndrome (MDS) (Appendix 1: MDS Classification) - MDS at any stage, based on either one of the following classifications:
Acute Myelogenous Leukemia
Patients with acute leukemia are included in this trial in remission, refractory or relapsed disease.
Transfusion dependence will be defined as greater than ONE transfusion of platelets or red blood cells in the last year prior to evaluation on protocol.
Donor choices will be determined by the investigators at each of the centers according to their own institutional criteria.
All patients evaluated at trial sites and eligible for this trial by virtue of disease and lack of an HLA-genotypically matched related donor will be captured in the database of this trial. Patients who will be enrolled on this protocol must have one of the following donor choices:
HLA-compatible Unrelated volunteer donors
Patients who do not have a related HLA-matched donor but have an unrelated donor who is either matched at all A, B, C and DRB1 (8/8) loci or who is mismatched at 1/8 loci (A, B, C or DRB1) (7/8) as tested by DNA analysis (high resolution), will be eligible for entry on this protocol.
HLA-mismatched Related donors
Patients who do not have a related or unrelated HLA-compatible donor must have a healthy family member who is at least HLA-haplotype identical to the recipient. First degree related donors must have a normal DEB test.
The donor must be healthy and willing and able to receive a 4-6 day course of G-CSF and undergo 1-3 daily leukaphereses.
Related and Unrelated donors must be medically evaluated and fulfill the criteria for collection of PBSCs as per institutional guidelines.
Patients and donors may be of either gender or any ethnic background.
Patients must have a Karnofsky adult, or Lansky pediatric performance scale status > or = 70%.
At the time of referral for transplantation, patients must have no co-existing medical problems that would significantly increase the risk of the transplant procedure.
Patients must have adequate physical function measured by :
Each patient must be willing to participate as a research subject and must sign an informed consent form. Parent or legal guardians of patients who are minors will sign the informed consent form. Assents will be obtained as age appropriate.
Female patients and donors must not be pregnant or breastfeeding at the time of signing consent. Women must be willing to undergo a pregnancy test prior to transplant and avoid becoming pregnant while on study.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Faird Boulad, MD | Memorial Sloan Kettering Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital Boston | Boston | Massachusetts | 02115 | United States | ||
| Memorial Sloan Kettering Cancer Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31851762 | Derived | van Hoogdalem MW, Emoto C, Fukuda T, Mizuno T, Mehta PA, Vinks AA. Population pharmacokinetic modelling of busulfan and the influence of body composition in paediatric Fanconi anaemia patients. Br J Clin Pharmacol. 2020 May;86(5):933-943. doi: 10.1111/bcp.14202. Epub 2020 Jan 23. | |
| 28179273 | Derived | Mehta PA, Davies SM, Leemhuis T, Myers K, Kernan NA, Prockop SE, Scaradavou A, O'Reilly RJ, Williams DA, Lehmann L, Guinan E, Margolis D, Baker KS, Lane A, Boulad F. Radiation-free, alternative-donor HCT for Fanconi anemia patients: results from a prospective multi-institutional study. Blood. 2017 Apr 20;129(16):2308-2315. doi: 10.1182/blood-2016-09-743112. Epub 2017 Feb 8. |
| Label | URL |
|---|---|
| Memorial Sloan-Kettering Cancer Center | View source |
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This is a multicenter site and MSK is the site responsible for data collection and analysis for all sites.
11 participants were enrolled at Memorial Sloan Kettering Cancer Center. The remaining 34 participants were enrolled at the participating institutions. This makes a total of 45 participants enrolled and treated on this study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Chemotherapy-based Cytoreductive Regimen Plus a CD34+ Selected | This phase II trial is designed to investigate the safety and efficacy of a chemotherapy-based cytoreductive regimen plus a CD34+ selected T-cell depleted peripheral blood stem cell (PBSC) stem cell transplant for the treatment of patients with Fanconi anemia and severe hematologic disease. Busulfan, fludarabine, & cyclophosphamide with immunosuppression with ATG and cyclosporine.: There are three parts in this transplant study. 1) There will be a pre-transplant - preparation - period to see if patient qualifies for the transplant study. This will be done as an outpatient and lasts 2-4 weeks. Once this is completed, there will be 2) the transplant period itself, during which the patient will be admitted and will be an inpatient. This period usually last for 4-6 weeks. Following that, there will be a 3) post transplant period, during which the patient will be watched carefully and monitored in clinic as an out patient. The post transplant period lasts from three months to one year. |
| 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 | Jun 18, 2014 |
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| Rockefeller University |
| OTHER |
| Fred Hutchinson Cancer Center | OTHER |
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|
| CliniMACS device | Device | CD34+ T-cell depleted peripheral blood stem cell transplant |
|
| 3 years |
| New York |
| New York |
| 10065 |
| United States |
| The Rockefeller University | New York | New York | 10065 | United States |
| Cincinnati Children's Hospital | Cincinnati | Ohio | 45229 | United States |
| Fred Hutchinson Cancer Research Center | Seattle | Washington | 98109 | United States |
| Children's Hospital of Wisconsin | Milwaukee | Wisconsin | United States |
| COMPLETED |
|
| NOT COMPLETED |
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Chemotherapy-based Cytoreductive Regimen Plus a CD34+ Selected | This phase II trial is designed to investigate the safety and efficacy of a chemotherapy-based cytoreductive regimen plus a CD34+ selected T-cell depleted peripheral blood stem cell (PBSC) stem cell transplant for the treatment of patients with Fanconi anemia and severe hematologic disease. Busulfan, fludarabine, & cyclophosphamide with immunosuppression with ATG and cyclosporine.: There are three parts in this transplant study. 1) There will be a pre-transplant - preparation - period to see if patient qualifies for the transplant study. This will be done as an outpatient and lasts 2-4 weeks. Once this is completed, there will be 2) the transplant period itself, during which the patient will be admitted and will be an inpatient. This period usually last for 4-6 weeks. Following that, there will be a 3) post transplant period, during which the patient will be watched carefully and monitored in clinic as an out patient. The post transplant period lasts from three months to one year. |
| 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 | Successful Neutrophil Engraftment | Posted | Count of Participants | Participants | 2 years |
|
|
| ||||||||||||||||||||||||||||||
| Primary | The Incidence of Early Transplant Related Mortality | Posted | Count of Participants | Participants | 2 years |
|
| |||||||||||||||||||||||||||||||
| Primary | The Incidence of Acute GvHD | Posted | Number | percentage of participants | 100 days |
|
| |||||||||||||||||||||||||||||||
| Primary | The Incidence of Chronic GvHD | Posted | Count of Participants | Participants | 2 years |
|
| |||||||||||||||||||||||||||||||
| Secondary | Overall Survival at 3 Years | Overall Survival is defined as time from date of transplant to event (death from any cause) or last follow-up. | Posted | Number | percentage of participants | 3 years |
|
| ||||||||||||||||||||||||||||||
| Secondary | Disease-free Survival at 3 Years | Defined as time from date of transplant to relapse, graft rejection or graft failure, or death. Primary non-engraftment is diagnosed when the participants fails to achieve an ANC >/= 500/ul at any time in the first 28 days post-transplant. For participants with MDS or AML, relapse will be analyzed as to type and genetic origin of the MDS/leukemic cells. These will be defined by an increasing number of blasts in the marrow over 5% by the presence of circulating peripheral blasts, or by the presence of blasts in any extramedullary site. Cytogenetic analysis of the marrow and/or peripheral blood will also be obtained for the diagnosis of relapse. | Posted | Number | percentage of participants | 3 years |
|
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 | Chemotherapy-based Cytoreductive Regimen Plus a CD34+ Selected | This phase II trial is designed to investigate the safety and efficacy of a chemotherapy-based cytoreductive regimen plus a CD34+ selected T-cell depleted peripheral blood stem cell (PBSC) stem cell transplant for the treatment of patients with Fanconi anemia and severe hematologic disease | 9 | 45 | 11 | 45 | 31 | 45 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bilirubin (hyperbilirubinemia) | Investigations | Systematic Assessment |
| ||
| Blood/Bone Marrow, Other | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Cardiopulmonary arrest, cause unknkown | Cardiac disorders | Systematic Assessment |
| ||
| Confusion | Psychiatric disorders | Systematic Assessment |
| ||
| Death NOS | General disorders | Systematic Assessment |
| ||
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Gastrointestinal, other | Gastrointestinal disorders | Systematic Assessment |
| ||
| Hemorrhage, Oral cavity | Gastrointestinal disorders | Systematic Assessment |
| ||
| Hemorrhage, Respiratory tract NOS | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Hemorrhage, Stoma (GI) | Gastrointestinal disorders | Systematic Assessment |
| ||
| Hypoxia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Ileus, GI (func obstruction of bowel) | Gastrointestinal disorders | Systematic Assessment |
| ||
| Inf norm ANC/gr1/2 neut-Blood | Infections and infestations | Systematic Assessment |
| ||
| Inf norm ANC/gr1/2 neut-Meningitis(meninges) | Infections and infestations | Systematic Assessment |
| ||
| Inf norm ANC/gr1/2 neut-Myositis infection(muscle) | Infections and infestations | Systematic Assessment |
| ||
| Infection w/ Gr 3/4 neut, Blood | Infections and infestations | Systematic Assessment |
| ||
| Infection, other | Infections and infestations | Systematic Assessment |
| ||
| Mucositis (Clin exam)- Oral cavity | Gastrointestinal disorders | Systematic Assessment |
| ||
| Neurology - Other (specify) | Nervous system disorders | Systematic Assessment |
| ||
| Neuropathy: motor | Nervous system disorders | Systematic Assessment |
| ||
| Pneumonitis/pulm infiltrates | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Pulm/upp respiratory - Other (spec) | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Pulmonary hypertension | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Seizure | Nervous system disorders | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Aspartate aminotransferase increased | Investigations | Systematic Assessment |
| ||
| Bicarbonate, serum-low | Investigations | Systematic Assessment |
| ||
| Blood bilirubin increased | Investigations | Systematic Assessment |
| ||
| Sodium, high (hypernatremia) | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Glucose, low (hypoglycemia) | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hypermagnesemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Mucositis (Clin exam)- Pharynx | Gastrointestinal disorders | Systematic Assessment |
| ||
| Phosphate, low (hypophosphatemia) | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Alanine aminotransferase increased | Investigations | Systematic Assessment |
| ||
| Infection, other | Infections and infestations | Systematic Assessment |
| ||
| Hyperglycemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| INR | Investigations | Systematic Assessment |
| ||
| Magnesium, high (hypermagnesemia) | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Magnesium, low (hypomagnesemia) | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Trglycrde, high (hypertriglyceridemia) | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Alkaline phosphatase | Investigations | Systematic Assessment |
| ||
| Potassium, high (hyperkalemia) | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| PTT | Investigations | Systematic Assessment |
| ||
| Albumin, low (hypoalbuminemia) | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Creatinine | Investigations | Systematic Assessment |
| ||
| Hemoglobin | Investigations | Systematic Assessment |
| ||
| Hypertension | Vascular disorders | Systematic Assessment |
| ||
| Leukocytes (total WBC) | Investigations | Systematic Assessment |
| ||
| Lymphopenia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Neutrophils/granulocytes (ANC/AGC) | Investigations | Systematic Assessment |
| ||
| Platelets | Investigations | Systematic Assessment |
| ||
| Sodium, low (hyponatremia) | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| AST, SGOT | Investigations | Systematic Assessment |
| ||
| Potassium, low (hypokalemia) | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| ALT, SGPT | Investigations | Systematic Assessment |
| ||
| Bilirubin (hyperbilirubinemia) | Investigations | Systematic Assessment |
| ||
| Glucose, high (hyperglycemia) | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Mucositis (Clin exam)- Oral cavity | Gastrointestinal disorders | Systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Farid Boulad | Memorial Sloan Kettering Cancer Center | 212-639-2429 | bouladf@mskcc.org |
| Mar 2, 2018 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D000741 | Anemia, Aplastic |
| D007938 | Leukemia |
| D009190 | Myelodysplastic Syndromes |
| D000740 | Anemia |
| ID | Term |
|---|---|
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D000080983 | Bone Marrow Failure Disorders |
| D001855 | Bone Marrow Diseases |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D002066 | Busulfan |
| C024352 | fludarabine |
| D003520 | Cyclophosphamide |
| D007165 | Immunosuppression Therapy |
| D016572 | Cyclosporine |
| ID | Term |
|---|---|
| D002072 | Butylene Glycols |
| D006018 | Glycols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D008698 | Mesylates |
| D000476 | Alkanesulfonates |
| D017738 | Alkanesulfonic Acids |
| D000473 | Alkanes |
| D006839 | Hydrocarbons, Acyclic |
| D006838 | Hydrocarbons |
| D013451 | Sulfonic Acids |
| D013456 | Sulfur Acids |
| D013457 | Sulfur Compounds |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D007167 | Immunotherapy |
| D056747 | Immunomodulation |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D007158 | Immunologic Techniques |
| D008919 | Investigative Techniques |
| D003524 | Cyclosporins |
| D010456 | Peptides, Cyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
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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 |
|
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