Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Rare Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Graft vs Host Disease

Lymphoma

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Non Lymphoblastic Leukemia

Homologous Wasting Disease

Acute Graft Versus Host Disease

Lymphosarcoma

All Drugs and Chemicals

Anti-Infective Agents

Antirheumatic Agents

Dermatologic Agents

Antibodies

Cyclosporine

Cyclosporins

Thymoglobulin

Immunoglobulins

Antilymphocyte Serum

Immunologic Factors

Immunosuppressive Agents

Thymoglobulin [Anti-Thymocyte Globulin (Rabbit)]

Medical Monitor

This study involves the use of a drug called Thymoglobulin, which is approved in the USA to treat kidney transplant rejection and in Canada to treat and to prevent kidney transplant rejection. Thymoglobulin is not approved for the treatment or prophylaxis of graft versus host disease in bone marrow transplantation. This study is to evaluate two (2) doses of Thymoglobulin and its safety and effectiveness when used with a "myeloablative" conditioning regimen prior to receiving a stem cell transplant (also called bone marrow transplantation) from a matched, related donor.

A myeloablative regimen is typically composed of chemotherapy and radiation and destroys the subject's existing bone marrow.

Subjects meeting all inclusion and exclusion criteria and who have a relative with matching (genetically similar) stem cells who are also willing to donate them (i.e. matched-related-donor) are eligible to participate in this study. Following myeloablative therapy, the donor's cells are then transplanted (i.e. infused) into the subject's blood stream.

One of the most common complications of this type of transplant is graft-versus-host disease (GvHD). This is a condition where the transplanted donor cells attack the transplant recipient's body. Treatments, such as cyclosporine, are used to minimize the risk of GvHD following stem cell transplantation.

To enter this study, subjects must be having a matched-related donor stem cell transplant. If a subject qualifies for entry into this study, he/she will be assigned to receive Thymoglobulin at a dose of 4.5 mg/kg or 8.5 mg/kg. The treatment assignment is random and is not chosen by the subject or their physician.

Subjects are admitted to the hospital for the transplant procedure and are treated with Thymoglobulin over 3-5 days just prior to receiving the donor stem cells. The subject will also receive standard GvHD prophylaxis with cyclosporine. Methotrexate, which is commonly used by transplant centers to minimize the risk of GvHD, will not be used in this study.

Subjects will be monitored during treatment with Thymoglobulin and during the transplant hospitalization. Additional subject monitoring occurs at month 1, 100 days and 6 months following the transplant.

Approximately 60 study subjects from approximately 14 transplant centers in the United States and Canada will be enrolled.

Thymoglobulin to Prevent Acute Graft vs. Host Disease (GvHD) in Patients With Acute Lymphocytic Leukemia (ALL) or Acute Myelogenous Leukemia (AML) Receiving a Stem Cell Transplant

Pilot Trial of Two Dose Levels of Thymoglobulin as Part of a Myeloablative-Conditioning for a Human Leukocyte Antigen (HLA) Identical Matched Related Donor (MRD) Stem Cell Transplant (SCT) With Cyclosporine (CSa) as Post-transplant Graft vs. Host Disease (GvHD) Prophylaxis

Genzyme, a Sanofi Company

Antineoplastic Agents

Venetoclax

Decitabine

Uric Acid

Antimetabolites

Enzyme Inhibitors

Venetoclax will be given with a 3-day ramp up beginning with 100 mg dose on Day 1, with 200mg on Day 2, to reach the final dose of 400 mg on Day 3 of Cycle 1. Venetoclax will be continued at 400 mg daily. Tumor lysis prophylaxis will be administered from day -4, cycle 1 (oral uric acid reducing agent and hydration with at least 1.5 L/day).Decitabine will be administered at the dose of 20 mg/sqm intravenously from day 1 to day 5 every 28 days (VEN-DEC) for 2 cycles.

The prognosis of acute myeloid leukemia (AML) patients aged over 60 years is poor and allogeneic stem cell transplantation (allo-SCT) is the only curative option.The association VEN-DEC is a promising combination therapy for AML elderly patients who are fit and eligible for allo-SCT.

Venetoclax and Decitabine

Domenico Russo, MD

This trial is a no profit, prospective, phase II, multicentre, non-randomised, uncontrolled, single group assignment, open label study to evaluate the safety and efficacy of the "chemo-free" combination Venetoclax plus Decitabine (VEN-DEC) as "bridge" to allo-SCT in elderly (≥ 60 - \< 75 years) AML patients. The primary objective is to evaluate the proportion of elderly (≥60 - \<75 years) patients with newly diagnosed AML, eligible for allo-SCT, treated with the "chemo-free" combination Venetoclax plus Decitabine (VEN-DEC) who get allo-SCT in CR/Cri/MLFS.

This trial is a no profit, prospective, phase II, multicentre, non-randomised, uncontrolled, single group assignment, open label study to evaluate the proportion of elderly (≥60 - \<75 years) patients with newly diagnosed AML, eligible for allo-SCT, treated with the "chemo-free" combination Venetoclax plus Decitabine (VEN-DEC) who get allo-SCT in CR/CRi/MLFS, organized under the auspices of the Gruppo Italiano TRapianti di Midollo Osseo (GITMO) that involves the prinicipla centres active in transplantation of any kind of stem cells in Italy. The target for this study is 100 patients.

Biologic characterization of AML will be performed at each participating Center by flow cytometry, cytogenetics and RT-qPCR on target genes (FLT3, NPM1A, WT1,) at disease onset. MRD monitoring will be performed at each participating Center by flow cytometry, cytogenetics and RT-qPCR (routine assessment) at the time of CR/CRi/MLFS before allo-SCT and during follow up (at least 4 timepoints: +100 days, +180 days, +1 year and +2 years from allo-SCT).

Genomic analysis by NGS gene-panel (Sophia Genetics) exploring the mutational status of the genes involved in of AML will be centralized in Brescia Laboratory at the enrollment into the study (diagnosis) and at the time of no response (PR/NR), before allo-SCT in patients in CR/CRi/MLFS and in case of relapse, at any time.

Primary Objectives To evaluate the proportion of elderly (≥60 - \<75 years) patients with newly diagnosed AML eligible for allo-SCT treated with the "chemo-free" combination Venetoclax plus Decitabine (VEN-DEC) who get allo-SCT in CR/CRi/MLFS.

Secondary Objectives

* Incidence and severity of adverse drug reactions (ADR) classified by System Organ Class (SOC) and preferred term (PT) from start treatment with Ventoclax and Decitabine to allo-SCT
* Efficacy of VEN-DEC combination
* Evaluation of the outcome of allo-SCT in term of:1) Incidence of graft failure at day +30, +100 from allo-SCT2) Incidence of Non-Relapse Mortality (NRM) at day +100, 1 year and 2 years from allo-SCT3) Incidence and severity of acute GVHD at day +100 from allo-SCT4) Incidence and severity of chronic GVHD at 1 year and 2 years from allo-SCT5) Probability of GRFS (GVHD free, relapse free survival) at 1 and 2 years from allo-SCT
* Relapse incidence (RI) at 1 year and 2 years from allo-SCT
* Disease-free survival (DFS) at 1 and 2 years from allo-SCT
* Overall Survival (OS) at 1 and 2 years from allo-SCT
* Correlation of immunophenothype, cytogenetic, molecular and NGS-genomic profiles with sensitivity (CR - CRi - MLFS) or resistance (PR/NR) to "chemo-free" combination Venetoclax plus Decitabine (VEN-DEC)
* Correlation of immunophenothype, cytogenetic, molecular and NGS-genomic profiles with the outcome of allo-SCT in terms of NRM, probability of RI, DFS, OS.

This study has 2 endpoints

Primary Endpoint Proportion of elderly (≥60 - \<75 years) patients with newly diagnosed AML eligible for allo-SCT treated with the "chemo-free" combination Venetoclax plus Decitabine (VEN-DEC) who get allo-SCT in CR/CRi/MLFS.

Secondary Endpoints

* Efficacy of VEN-DEC combination
* Cumulative incidence of graft failure at +30 days, +100 days from transplant
* Outcome of allo-SCT in term of NRM at day +100, 1 year and 2 years from allo-SCT
* Cumulative incidence and severity of acute GvHD at 100 days after transplant
* Cumulative incidence and severity of chronic GvHD at 1 and 2 years post transplant
* RI at 1 and 2 year after transplantation from days of transplant.
* OS at 1 and 2 years post transplant
* DFS at 1 and 2 years post transplant
* 1 and 2 year probability of GRFS
* Correlation of immunophenothype, cytogenetic, molecular and NGS-genomic profiles with sensitivity (CR - CRi - MLFS) or resistance (PR-NR) to "chemo-free" combination Venetoclax plus Decitabine (VEN-DEC)
* Correlation of immunophenothype, cytogenetic, molecular and NGS-genomic profiles with the outcomes of allo-SCT: NRM, RI, DFS, OS.

Biologic characterization of AML will be performed at each participating Center by flow cytometry, cytogenetics and RT-qPCR on target genes (FLT3, NPM1A, WT1,...) at disease onset. MRD monitoring will be performed at each participating Center by flow cytometry, cytogenetics and RT-qPCR (routine assessment) at the time of CR/CRi/MLFS, before allo-SCT and during follow up (at least 4 timepoints: +100 days, +180 days, +1 year and +2 years from allo-SCT).Genomic analysis by NGS gene-panel (Sophia Genetics) exploring the mutational status of the genes involved in of AML will be centralized in Brescia Laboratory at the enrollment into the study (diagnosis) and at the time of no response (PR/NR), before allo-SCT in patients in CR/CRi/MLFS and in case of relapse, at any time.

Venetoclax will be given with a 3-day ramp up beginning with 100 mg dose on Day 1 to reach the final dose of 400 mg on Day 3 of Cycle 1. Venetoclax will be continued at 400 mg daily. Tumor lysis prophylaxis will be administered from day -4, cycle 1 (oral uric acid reducing agent and hydration with at least 1.5 L/day).

Decitabine will be administered at the dose of 20 mg/sqm intravenously from day 1 to day 5 every 28 days (VEN-DEC) for 2 cycles. The response will be assessed after the 2nd Cycle VEN-DEC according to ELN criteria. In case of CR/CRi/MLFS, patients will undergo allo-SCT within 2 months. A maximum of two additional VEN-DEC cycles is permitted while waiting for allo-SCT. In case of NR or PR after the 2nd Cycle VEN-DEC, two additional cycles of VEN-DEC will be administered and patients achieving CR/CRi/MLFS will undergo allo-SCT as soon as possible (within 2 months). Patients with NR or PR will be treated according to single center policy, including also allo-SCT.

Patients achieving Morphologic Leukemia-free State (MLFS) will be considered responsive patients, since the percentage of BM blast cells is \< 5%. These patients may undergo allo-SCT after 2 - 4 cycles of VEN-DEC.Granulocyte colony stimulating factor (G-CSF) will be allowed during VEN-DEC in case of febrile neutropenia. Whenever clinically indicated, G-CSF use has to be notified tin the CRF.

Population for analysis The population for analysis in this trial will be the Intent to Treat (ITT) population. All patients who have received at least one therapeutic dose of study medications will be included in the ITT analysis.

Sample size calculation The study is designed as a Simon optimal two-Stage Phase II clinical trial, including a planned futility check: after enrollment of the first 30 patients the Investigator will pause for the futility check is at that time point the target 4 patients will not yet be admitted to allo-SCT. Based on the current literature, less than 10% of elderly (\>60 \<75 years) AML patients can be submitted to allo-SCT, due to no-response to induction conventional chemotherapy (NR or PR) and /or to treatment toxicity. Therefore, to test the null hypothesis (conventional chemotherapy) that p ≤0.10 versus the alternative (VEN-DEC) that p ≥0.20, the expected sample size is 89 patients, with a probability of early termination of 0.647, when true proportion is 0.1. Alpha error is 0.0478 and beta value 0.1982. If there are 3 or fewer patients submitted to allo-SCT in the first 30 enrolled patients, the trial will be terminated for futility. Otherwise, considering an overall 12% of drop-out rate, 70 additional patients will be accrued for a total of 100 patients: in the second stage 70 patients will only be enrolled if at least 4 patients of the first stage undergo allo-SCT. The null hypothesis will be rejected if 14 of more patients treated with VEN-DEC will be submitted to allo-SCT in CR/CRi/MLFS.

The study is considered completed when the 100th patient will be enrolled. It is planned to complete the total enrollment (100 patients) in 18 months, starting from the first patient enrolled.

The follow-up according to the protocol is 2 years for each patient from the day of enrollment. In the transplanted patients the pre-transplant period will be followed by 2 years post-transplant follow-up

The study will be performed in 4 years from the first patient enrolled according to the following times:

18 moths for enrollment (from the first patient) and for database completion and cleaning 24 months of follow up. In the transplanted patients the pre-transplant period will be followed by 2 years post-transplant follow-up 6 months for statistical analysis, drafting of the final report and paper.

The study will be conducted in accordance with the ethical principles derived from the Declaration of Helsinki, the CGP and regulations.

Before starting the study, the protocol will be sent to the Ethics Committee, in accordance with the current legislation on interventional study.

The protocol has been written and the study will be conducted according to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Harmonized tripartite Guideline for GCP, issued by European Union. IRB approval must be obtained prior to the starting of the trial. ICF must be submitted to appropriate authority or IRB together with clinical protocol for written approval.

These patients may undergo allo-SCT after 2 - 4 cycles of VEN-DEC

Venetoclax and Decitabine Assessment in Patients (≥60 - <75 Years) With Newly Diagnosed AML Eligible for Allo-SCT

Phase II Study on Venetoclax (VEN) Plus Decitabine (DEC) (VEN-DEC) for Elderly (≥60 <75years) Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) Elegible for Allogeneic Stem Cell Transplantation (Allo-SCT)

response to VEN-DEC induction will be assessed on bone marrow according to the ELN Guidelines (13), as following: - CR without minimal residual disease (CR-MRD neg); (Complete Remission ) bone marrow blasts 5%) - CR remission with incomplete hematologic recovery (CRi): Morphologic Leukemia-free State (MLFS) Partial Remission (PR): All hematologic criteria of CR; decrease of bone marrow blast percentage to 5% to 25%; and decrease of pretreatment bone marrow blast percentage by at least 50%; - Primary refractory disease/Non response (NR): No CR or CRi after 2 courses of VEN-DEC; excluding patients with death in aplasia or death due to indeterminate cause;

Proportion of patients who undergo to allo-SCT in first CR/CRi/MLFS

Percentage of patients with Neutrophil engraftment and percentage of patients with platelet engraftment

at 2 year post transplant. OS is defined as the time from transplant to the date of death due to any cause or to the last date the patient was known to be alive (censored observation) or to the date of the data cut-off for final analysis

NRM is defined as death due to any other cause than progression of malignancy after allogeneic stem cell transplantation. Cumulative incidence will be estimated at 100 days

NRM is defined as death due to any other cause than progression of malignancy after allogeneic stem cell transplantation. Cumulative incidence will be estimated at 180 days

NRM is defined as death due to any other cause than progression of malignancy after allogeneic stem cell transplantation. Cumulative incidence will be estimated at 365 days

Gruppo Italiano Trapianto di Midollo Osseo

Symptoms and General Pathology

Diseases and Abnormalities at or Before Birth

Infections

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Digestive System Diseases

Nutritional and Metabolic Diseases

Syndrome

Preleukemia

Leukemia, Myelomonocytic, Juvenile

Myelodysplastic Syndromes

Anemia, Sickle Cell

Anemia

Thrombocytopenia

Thalassemia

beta-Thalassemia

Acquired Immunodeficiency Syndrome

HIV Infections

Immunologic Deficiency Syndromes

Anemia, Aplastic

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Neutropenia

Lymphocytosis

Bone Marrow Failure Disorders

Pancytopenia

Macrophage Activation Syndrome

Hemoglobinopathies

Primary Immunodeficiency Diseases

Histiocytosis, Langerhans-Cell

Histiocytosis

Shwachman-Diamond Syndrome

Anemia, Diamond-Blackfan

Bone Marrow Diseases

Precancerous Conditions

Myeloproliferative Disorders

Chronic Disease

Disease Attributes

Myelodysplastic-Myeloproliferative Diseases

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Sickle Cell Anemia

Chronic Graft Versus Host Disease

Beta-thalassemia

Aplastic Anemia

Chronic Myeloid Leukemia

Granulocytopenia

Langerhans Cell Histiocytosis

Diamond-Blackfan Anemia

Familial Hemophagocytic Lymphohistiocytosis

Severe Congenital Neutropenia

Sickle Beta Thalassemia

Chronic Myeloproliferative Disorders

Myelodysplastic/myeloproliferative Disease

Pharmaceutical Solutions

Anti-Inflammatory Agents

Hematinics

Antiemetics

Neuroprotective Agents

Gastrointestinal Agents

Tacrolimus

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Melphalan

Prednisolone

Sirolimus

Busulfan

Liver Extracts

Methylprednisolone

Thiotepa

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

Alemtuzumab

Antineoplastic Agents, Alkylating

Alkylating Agents

Calcineurin Inhibitors

Glucocorticoids

Hormones

Hormone Antagonists

Protective Agents

Antineoplastic Agents, Hormonal

Antineoplastic Agents, Immunological

Patients will start their pre-conditioning regimen on 8 days before scheduled transplant. Fractionated total body irradiation (TBI) will be administered twice daily on the 6th, 7th, and 8th before transplant. Patients will receive Thiotepa on the 4th and 5th day before transplant, Cyclophosphamide on the 2nd and 3rd day before transplant, and Alemtuzumab on the 1st-5th day(s) before transplant. Then the stem cell infusion will be performed (allogeneic family member or ≥ 8/10 HLA matched adult unrelated donor peripheral blood stem cell transplantation with CD34 Selection using CliniMACS CD34+ Reagent System). GVHD prophylaxis will consist of tacrolimus only. Tacrolimus administration will begin on the day after transplant, and methylprednisolone will start on day -5.

Patients will start their pre-conditioning regimen 9 days before their scheduled transplant. Patients will receive busulfan twice daily on the 5th-8th day before transplant, and Melphalan on the 2nd-4th days before transplant and Alemtuzumab on the 1st-5th day before transplant. Subjects will then undergo with their stem cell infusion (allogeneic family member or ≥ 8/10 HLA matched adult unrelated donor peripheral blood stem cell transplantation with CD34 Selection using CliniMACS CD34+ Reagent System) and GVHD prophylaxis will consist of tacrolimus only. Tacrolimus administration will begin on the day after their transplant, and methylprednisolone will start on day -5.

Patients will begin tacrolimus 8 days pre-transplant, and then will receive alemtuzumab on the 3rd-7th day pre-transplant; busulfan twice daily on the 5th-8th day pre-transplant; and fludarabine on the 2nd-7th day pre-transplant. Methylprednisolone will start on day -7.The stem cell infusion will be performed (with CD34 Selection using CliniMACS CD34+ Reagent System). GVHD prophylaxis will consist of tacrolimus or sirolimus. For patients with a history of hepatic toxicity and/or high-risk for veno-occlusive disease or other liver toxicity post stem cell transplant, melphalan at 70 mg/m2 will be substituted for Busulfan, followed by fludarabine on the 2nd-7th day before transplant and alemtuzumab on the 3rd-7th day before transplant.

The CliniMACS® Reagent System (Miltenyi Biotec, Germany), is a semi-automated immunomagnetic cell selection medical device that is used in vitro to select and enrich specific cell populations in a closed, sterile environment. The system is comprised of a computer controlled medical device containing a permanent magnet, a closed-system sterile tubing set containing columns coated with a ferromagnetic matrix, and a magnetic cell specific labeling reagent.

CliniMACS CD34+ Reagent System

Standard of care: Thiotepa should be diluted in normal saline (NS) (1-5 mg/ml) and infused over 2 hrs on Days -5, -4. IV fluids should be at maintenance rate (1500 ml/m2). It is recommended that total parental nutrition not being used during Thiotepa administration as amino acid infusions may interfere with Thiotepa metabolism.

Standard of care: Cyclophosphamide (Cytoxan) should be infused over one hour. The drug can be diluted in dextrose water solvent (D5W), NS, or other solutions (250cc) to a maximum concentration of 20 mg/mL.

Standard of care: Each dose of alemtuzumab is to be diluted in D5W or NS (maximum concentration: 0.3 mg/mL) for IV infusion over two hours.

Standard of care: Tacrolimus dosing will be 0.03mg/kg/24 hours as continuous IV infusion or 0.12 mg/kg/day po divided Q8-12 hr

Standard of care: Melphalan 45mg/m2 (1.5 mg/kg IV for children \<1 year of age or \<10 kg) diluted in 0.9% NS to a concentration of 0.1- 0.45mg/ml, given IV over 30 minutes.

Standard of care: Busulfan will be given IV in 0.9% sodium chloride or D5W to a final solution for infusion equal to 10 times the volume of diluent to Busulfex (to a concentration \>0.5 mg/mL), through a central venous access device over 2 hours.

Standard of care: Fludarabine will be given IV in 50-100 ml of D5W or 0.9% sodium chloride, over 30 minutes.

Standard of care: Methylprednisolone will be give IV slow infusion over 15-30 minutes.

Jody Campbell, MPA

Desmarie Sherwood

Diane George, MD

The purpose of this study is to learn more about the effects of (classification determinant) CD34+ stem cell selection on graft versus host disease (GVHD) in children, adolescents, and young adults. CD34+ stem cells are the cells that make all the types of blood cells in the body. GVHD is a condition that results from a reaction of transplanted donor T-lymphocytes (a kind of white blood cell) against the recipient's body and organs. Study subjects will be offered treatment involving the use of the CliniMACS® Reagent System (Miltenyi Biotec), a CD34+ selection device to remove T-cells from a peripheral blood stem cell transplant in order to decrease the risk of acute and chronic GVHD.

This study involves subjects who are diagnosed with a malignant disease, that has either failed standard therapy or is unlikely to be cured with standard non-transplant therapy, who will receive a peripheral blood stem cell transplant. A malignant disease includes the following: Chronic Myeloid Leukemia (CML) in chronic phase, accelerated phase or blast crisis; Acute Myelogenous Leukemia (AML); Myelodysplastic Syndrome (MDS); Juvenile Myelomonocytic Leukemia (JMML); Acute Lymphoblastic Leukemia (ALL); or Lymphoma (Hodgkin's and Non-Hodgkin's).

Graft versus host disease (GVHD) is one of the serious complications following allogeneic stem cell transplantation. The incidence and severity of GVHD increase with the degree of HLA incompatibility between the host and donor. The most reliable way to prevent acute and chronic GVHD is to remove T cells from the graft. However, the incidence of graft failure increases with the efficiency of T cell depletion and low T cell numbers are predictive of graft failure. Immunomagnetic selection of HLA-mismatched CD34+ progenitor cells has demonstrated high levels of T cell depletion and successful engraftment in adult and pediatric patients with the malignant and nonmalignant disease.

CD34+ (Malignant) Stem Cell Selection for Patients Receiving Allogenic Stem Cell Transplant

CD34+ Stem Cell Selection for Patients Receiving a Matched or Partially Matched Family or Unrelated Adult Donor Allogeneic Stem Cell Transplant for Malignant Disease

Acute GVHD will be assessed and graded with standard NCI grading criteria.Evaluated daily while hospitalized, then weekly (1-60 days post-transplant), as clinically indicated (60-365 days post transplant), then 1 year, 1.5 years, 2 years and yearly (366+ days post-transplant)

Will be assessed multiple times while hospitalized, 1-60 days post transplant, 100 days post-transplant, 180 days post-transplant, and 1-year post transplant. Neutrophil engraftment is defined as the first of three days following the neutrophil nadir with an absolute neutrophil count above 500/mm3.

Immune reconstitution studies will be conducted (For T-cell, B-cell, natural killer (NK)-cell and immunoglobulins) 60 days post-transplant, 100 days post-transplant, 150 days post-transplant, 180 days post-transplant, 270 days post-transplant, 1-year post-transplant, and 2 years post transplant.

Will be assessed weekly or more as indicated until 84 or 100 days post-transplant, then as clinically indicated.

Will be assessed multiple times while hospitalized, 1-60 days post transplant, 100 days post-transplant, 180 days post-transplant, and 1-year post transplant.

Chronic GVHD will be assessed and graded with standard NCI grading criteria.

Acute GVHD will be assessed and graded with standard NCI grading criteria.

Chronic GVHD will be assessed and graded with standard NCI grading criteria. Evaluated daily while hospitalized, then weekly (1-60 days post-transplant), as clinically indicated (60-365 days post transplant), then 1 year, 1.5 years, 2

Primary graft rejection is defined as the presence of \< 20% donor cells

The presence of \< 20% donor derived hematopoietic cells in peripheral blood

Diane George

Assistant Professor of Pediatrics, Department of Pediatrics Onc/BMT/Hem

Hematologic Neoplasms

Preparative regimen of 1)Busulfex 3.2 mg/kg/day for 2 days, infused over 3 hours, on Day-6 and Day-5 2)Fludarabine 30 mg/m2/day for 5 days on Day-6 to D-2 and 3) Alemtuzumab 10 mg/day IV on days - 5 to -1

Busulfex 3.2 mg/kg/day for 2 days infused over 3 hours, Days -6 and Day-5 Fludarabine 30 mg/m2/day for 5 days on Day -6 to D-2 Alemtuzumab 10 mg/day IV on Days -5 to -1

Busulfex, Fludarabine, ALemtuzumab

George Selby, MD

To evaluate engraftment and toxicity of a reduced intensity preparative regimen for patients who receive a matched related or unrelated donor allogeneic stem cell transplant (ASCT) for malignant hematological diseases

Primary Endpoints:

1. Engraftment of donor cells
2. Regimen related toxicities

Secondary Endpoints:

1. Disease-free survival
2. Overall survival

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Thymoglobulin to Prevent Acute Graft vs. Host Disease (GvHD) in Patients With Acute Lymphocytic Leukemia (ALL) or Acute Myelogenous Leukemia (AML) Receiving a Stem Cell Transplant	NCT00088543	Acute Myelogeno... Acute Lymphocyt... Graft vs. Host ...	Thymoglobulin [... Thymoglobulin [...	18 Years - 55 Years	Sanofi
Venetoclax and Decitabine Assessment in Patients (≥60 - <75 Years) With Newly Diagnosed AML Eligible for Allo-SCT	NCT04476199	Acute Myeloid L...	Venetoclax and ...	60 Years - 75 Years	Gruppo Italiano Trapianto di Midollo Osseo
Thymoglobulin to Prevent Acute Graft vs. Host Disease (GvHD) in Patients With Acute Lymphocytic Leukemia (ALL) or Acute Myelogenous Leukemia (AML) Receiving a Stem Cell Transplant	NCT00088543	Acute Myelogeno... Acute Lymphocyt... Graft vs. Host ...	Thymoglobulin [... Thymoglobulin [...	18 Years - 55 Years	Sanofi
Venetoclax and Decitabine Assessment in Patients (≥60 - <75 Years) With Newly Diagnosed AML Eligible for Allo-SCT	NCT04476199	Acute Myeloid L...	Venetoclax and ...	60 Years - 75 Years	Gruppo Italiano Trapianto di Midollo Osseo
CD34+ (Malignant) Stem Cell Selection for Patients Receiving Allogenic Stem Cell Transplant	NCT02061800	Chronic Myeloid... Acute Myelogeno... Myelodysplastic... Juvenile Myelom... Acute Lymphobla... Lymphoma (Hodgk...	CliniMACS CD34+... Thiotepa Cyclophosphamid... Alemtuzumab Tacrolimus Melphalan Busulfan Fludarabine Methylprednisol...	- 22 Years	Columbia University
Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation for Malignant Hematological Diseases	NCT00582894	Hematological N... Hematopoietic S...	Busulfex, Fluda...	18 Years - 75 Years	University of Oklahoma
Thymoglobulin to Prevent Acute Graft vs. Host Disease (GvHD) in Patients With Acute Lymphocytic Leukemia (ALL) or Acute Myelogenous Leukemia (AML) Receiving a Stem Cell Transplant	NCT00088543	Acute Myelogeno... Acute Lymphocyt... Graft vs. Host ...	Thymoglobulin [... Thymoglobulin [...	18 Years - 55 Years	Sanofi

Spots Global Cancer Trial Database for allogenic stem cell transplant