Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Rare Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Hematologic Neoplasms

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Leukemia, Myelomonocytic, Juvenile

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Infective Agents

Cyclophosphamide

Mycophenolic Acid

Tacrolimus

Busulfan

Immunosuppressive Agents

Mesna

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Calcineurin Inhibitors

Enzyme Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antitubercular Agents

Patients with AML and MDS:

Days -6 through -3: Busulfan q 5-6h IV q24h x 4 days

Days -2 and -1: Cyclophosphamide 50mg/kg/day IV x 2 days+ Mesna 40 mg/kg/day IV

For patients with ALL and lymphoblastic lymphoma:

Days -5 through -4: Cyclophosphamide 50mg/kg/day IV q24h x 2 days+Mesna 40 mg/kg/day IV

Days -3 through -1: TBI 200 Centigray (cGy) twice a day for 3 days

All patients Day 0: Infuse unmanipulated bone marrow

Day +3 and +4: Cyclophosphamide 50 mg/kg/day IV + Mesna 40 mg/kg IBW/day IV

Day +5: Begin tacrolimus 0.015mg/kg IBW/dose IV over 4 hours q 12h and mycophenolate mofetil (MMF)15mg/kg po/IV tid with maximum daily dose 3 gm/day

Day +30: Assess chimerism and disease status in bone marrow

Day +35: Discontinue MMF

Day +60: Assess chimerism and disease status in bone marrow

Day 180: Discontinue tacrolimus

Unmanipulated Bone Marrow

Mycophenolate mofetil

Heather Symons, MD, MHS

This is a multi-institutional phase II haploidentical T cell replete bone marrow transplant (BMT) study in children with high-risk leukemia. The myeloablative conditioning regimen prescribed will be Total body irradiation (TBI)-based for lymphoid leukemia and busulfan-based for myeloid leukemia. Our goal is to establish an easily exportable, inexpensive platform for haplotransplantation that has a safety profile equivalent to matched related and unrelated BMTs. The primary objective will be to estimate the incidence of 6-month non-relapse mortality (NRM), hypothesizing that NRM is \< 18%.

This is a phase II prospective study designed to evaluate the incidence of 6 month non- relapse mortality, safety, and feasibility of haploidentical bone marrow transplantation (BMT) after myeloablative conditioning with post-transplant Cy. Conditioning regimens include a total body irradiation (TBI)-based prep for lymphoid leukemias and a chemotherapy based prep for myeloid leukemias.

To estimate the incidence of non-relapse mortality at 180 days following myeloablative haploidentical BMT for children and young adults with high risk hematologic malignancies.

Myeloablative Haploidentical BMT With Post-transplant Cyclophosphamide for Pediatric Patients With Hematologic Malignancies

Pediatric Blood & Marrow Transplant Consortium (PBMTC) Phase II Myeloablative Haploidentical BMT With Post-transplantation Cyclophosphamide for Pediatric Patients With Hematologic Malignancies

Cumulative incidence (measured as a percentage) of non-relapse mortality at 180 days following myeloablative, Human Leukocyte Antigen (HLA)-mismatched bone marrow transplant (BMT) for patients with high risk hematologic malignancies.

Number of Participants with Donor Cell Engraftment at Day 60 following myeloablative, HLA-mismatched BMT.

Cumulative incidence (measured as a percentage) of acute GVHD grades 2-4 (overall) and grades 3-4 (severe).

Cumulative incidence (measured as a percentage) of chronic graft versus host disease (GVHD).

Incidence (measured as a percentage) of primary and secondary graft failure.

Number of participants who used steroid and non-steroid immunosuppressants to treat GVHD.

Duration of use of steroid and non-steroid immunosuppressants (in months) to treat GVHD.

Estimate incidence of overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), event-free survival, and relapse-free GVHD-free survival (GRFS) in patients receiving myeloablative, HLA-mismatched BMT for patients with high risk hematologic malignancies at 1 year. Incidence as a percentage.

Estimate incidence of overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), event-free survival, and relapse-free GVHD-free survival (GRFS) in patients receiving myeloablative, HLA-mismatched BMT for patients with high risk hematologic malignancies at 2 years. Incidence as a percentage.

Characterize immune reconstitution post myeloablative haploidentical BMT with Post transplantation cyclophosphamide (PT/Cy).

Time to neutrophil and platelet recovery in median days

Incidence of donor cell engraftment measured as the percentage of donor cell engraftment.

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Adverse events reported at each visit during time at transplant center and up to 180 days post-transplantation.

Patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS):

Days -6 through -3: Busulfan q 5-6h IV q24h x 4 days Days -2 and -1: Cyclophosphamide 50mg/kg/day IV x 2 days+ Mesna 40 mg/kg/day IV

For patients with acute lymphocytic leukemia (ALL) and lymphoblastic lymphoma:

Days -5 through -4: Cyclophosphamide 50mg/kg/day IV q24h x 2 days+Mesna 40 mg/kg/day IV Days -3 through -1: total body irradiation (TBI) 200 Centigray (cGy) twice a day for 3 days All patients Day 0: Infuse unmanipulated bone marrow Day +3 and +4: Cyclophosphamide 50 mg/kg/day IV + Mesna 40 mg/kg IBW/day IV Day +5: Begin tacrolimus 0.015mg/kg IBW/dose IV over 4 hours q 12h and mycophenolate mofetil (MMF)15mg/kg po/IV tid with maximum daily dose 3 gm/day Day +30: Assess chimerism and disease status in bone marrow Day +35: Discontinue MMF Day +60: Assess chimerism and disease status in bone marrow Day 180: Discontinue tacrolimus Cyclophosphamide: Chemotherapy administration TBI: Radiation Therapy Busulfan: Chemotherapy Administered Unmanipulated Bone Marrow: Bone Marrow Transplant Tacrolimus: Immunosuppressive Drug Administered Mycophenolate mofetil: Immunosuppressive Drug Administered

Haploidentical BMT With PTCy for Acute Leukemias and MDS

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Canada

United States

Region of Enrollment

Heather Symons, MD

Cumulative Incidence of Non-relapse Mortality

Patients with AML and MDS:

Days -6 through -3: Busulfan q 5-6h IV q24h x 4 days Days -2 and -1: Cyclophosphamide 50mg/kg/day IV x 2 days+ Mesna 40 mg/kg/day IV

For patients with ALL and lymphoblastic lymphoma:

Days -5 through -4: Cyclophosphamide 50mg/kg/day IV q24h x 2 days+Mesna 40 mg/kg/day IV Days -3 through -1: TBI 200 Centigray (cGy) twice a day for 3 days All patients Day 0: Infuse unmanipulated bone marrow Day +3 and +4: Cyclophosphamide 50 mg/kg/day IV + Mesna 40 mg/kg IBW/day IV Day +5: Begin tacrolimus 0.015mg/kg IBW/dose IV over 4 hours q 12h and mycophenolate mofetil (MMF)15mg/kg po/IV tid with maximum daily dose 3 gm/day Day +30: Assess chimerism and disease status in bone marrow Day +35: Discontinue MMF Day +60: Assess chimerism and disease status in bone marrow Day 180: Discontinue tacrolimus Cyclophosphamide: Chemotherapy administration TBI: Radiation Therapy Busulfan: Chemotherapy Administered Unmanipulated Bone Marrow: Bone Marrow Transplant Tacrolimus: Immunosuppressive Drug Administered Mycophenolate mofetil: Immunosuppressive Drug Administered

Number of Participants With Donor Cell Engraftment

Grades 2-4

Grades 3-4

Cumulative Incidence of Acute Graft Versus Host Disease (GVHD) Grades 2-4 and Grades 3-4

Cumulative Incidence of Chronic GVHD

Primary

Secondary

Primary and Secondary Graft Failure

Steroid immunosuppressants

Non-steroid immunosuppressants

Patients with AML and MDS:

Days -6 through -3: Busulfan q 5-6h IV q24h x 4 days

Days -2 and -1: Cyclophosphamide 50mg/kg/day IV x 2 days+ Mesna 40 mg/kg/day IV

For patients with ALL and lymphoblastic lymphoma:

Days -5 through -4: Cyclophosphamide 50mg/kg/day IV q24h x 2 days+Mesna 40 mg/kg/day IV

Days -3 through -1: TBI 200 Centigray (cGy) twice a day for 3 days

All patients Day 0: Infuse unmanipulated bone marrow

Day +3 and +4: Cyclophosphamide 50 mg/kg/day IV + Mesna 40 mg/kg IBW/day IV

Day +5: Begin tacrolimus 0.015mg/kg IBW/dose IV over 4 hours q 12h and mycophenolate mofetil (MMF)15mg/kg po/IV tid with maximum daily dose 3 gm/day

Day +30: Assess chimerism and disease status in bone marrow

Day +35: Discontinue MMF

Day +60: Assess chimerism and disease status in bone marrow

Day 180: Discontinue tacrolimus

Cyclophosphamide: Chemotherapy administration

TBI: Radiation Therapy

Busulfan: Chemotherapy Administered

Unmanipulated Bone Marrow: Bone Marrow Transplant

Tacrolimus: Immunosuppressive Drug Administered

Mycophenolate mofetil: Immunosuppressive Drug Administered

Steroid and Non-steroid Immunosuppressants

Four participants used immunosuppressants. Four used steroids and 2 of the 4 also used non-steroid. Duration of use for 3 participants using steroids was not recorded. One participant using non-steroid was not recorded.

Steroid and Non-steroid Immunosuppressants Use Duration

overall survival (OS)

progression-free survival (PFS)

disease-free survival (DFS)

event-free survival

Relapse-free GVHD-free survival (GRFS)

Survival

Blood samples collected were not analyzed due to lack of funding. No data was generated.

Immune Reconstitution

neutrophil

platelet

Time to Neutrophil and Platelet Recovery

Incidence of Donor Cell Engraftment

Overall Study

Symptoms and General Pathology

Infections

Respiratory Tract (Lung and Bronchial) Diseases

Neoplasm Metastasis

Syndrome

Lymphoma

Communicable Diseases

Leukemia, Lymphocytic, Chronic, B-Cell

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Philadelphia Chromosome

Hodgkin Disease

Preleukemia

Myelodysplastic Syndromes

Histiocytosis, Langerhans-Cell

Histiocytosis

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Chronic Myeloid Leukemia

Hodgkin Lymphoma

Langerhans Cell Histiocytosis

Fludarabine

Fludarabine phosphate

Rituximab

Melphalan

Thymoglobulin

Thiotepa

Clofarabine

Antilymphocyte Serum

Antineoplastic Agents, Immunological

Antimetabolites

Myeloablative Regimen: Rituxan 375 mg/m\^2 (B cell malignancy) by vein (IV) on Day -10; Busulfan AUC 4,000 IV either as an outpatient prior to admission or as an inpatient on Day -9; Clofarabine 30 mg/m\^2 IV Day -7 to Day -4; ATG 1.25 mg/Kg by vein on Day -4 and 1.75 mg/Kg by vein on Day -3; Fludarabine 10 mg/m\^2 IV on Days -7 to -4; Total Body Irradiation (TBI) 2 Gy on Day -3; with Cord Blood infusions on Day 0.

Reduced Intensity: Fludarabine 40 mg/m\^2 IV on Days -5 to -2; Melphalan 140 mg/m\^2 IV on Day -2; ATG 1.25 mg/Kg by vein on Day -4 and 1.75 mg/Kg by vein on Day -3; with Cord Blood infusions on Day 0.

140 mg/m2 by vein on Day -2 only for Fludarabine + Melphalan group.

10 mg/m2 by vein on Days -7 to -4 for Melphalan + Thiotepa + Fludarabine group, or 40 mg on Days -5 to -2 for Fludarabine + Melphalan group.

15 mg/kg (actual body weight with a maximum dose of 1 gram twice daily) by vein or by mouth twice a day from Days -3 to +100 in the absence of Graft vs Host Disease (GvHD).

Starting dose 0.03 mg/kg or 0.015 mg/kg (ideal body weight) by vein starting on Day -2 and tapered around Day +180 if no Graft vs Host Disease (GvHD) is present.

Cord blood infusion on Day 0. Each participant will receive cells from one unexpanded cord blood sample plus cells from a second cord blood sample that has undergone fucosylation.

Cord Blood Infusion

375 mg/m\^2 by vein on Day -10 for B cell malignancy.

1.25 mg/Kg by vein on Day -4.

1.75 mg/Kg by vein on Day -3.

Busulfan per standard of care, test dose either as an outpatient prior to admission or as an inpatient on Day -9. Busulfan pharmacokinetics performed with test dose and the first dose on Day -7 per standard of care. Doses of Days -5 and -4 subsequently adjusted to target an AUC of 4,000 microMol.min-1.

Total Body Irradiation (TBI)

Elizabeth Shpall, MD

The goal of this clinical research study is to learn if it is safe and feasible to transplant changed cord blood for patients with leukemia or lymphoma. Researchers also want to learn if this can help to control the disease.

The cord blood will be changed to make use of sugar that is found in small amounts in blood cells. It plays a role in signaling where in the body the transplanted cells should go to. Adding more sugars to the cord blood cells in the laboratory is designed to help the cord blood cells find their way faster to the bone marrow. This may help your blood counts to recover faster. This process is called fucosylation.

Anti-thymocyte globulin (ATG) is a protein that removes immune cells that cause damage to the body.

Clofarabine is designed to interfere with the growth and development of cancer cells.

Fludarabine is designed to interfere with the DNA (genetic material) of cancer cells, which may cause the cancer cells to die. This chemotherapy is also designed to block your body's ability to reject the donor's bone marrow cells.

Melphalan and busulfan are designed to bind to the DNA of cells, which may cause cancer cells to die.

Mycophenolate mofetil (MMF) and tacrolimus are designed to block the donor cells from growing and spreading in a way that could cause graft versus host disease (GVHD -- a condition in which transplanted tissue attacks the recipient's body). This may help to prevent GVHD.

Rituximab is designed to attach to cancer cells, which may cause them to die.

Central Venous Catheter Placement:

You will first have a central venous catheter (CVC) placed. A CVC is a sterile flexible tube that will be placed into a large vein while you are under local anesthesia. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form for it.

The chemotherapy, some of the other drugs in this study, and the cord blood transplant will be given by vein through your CVC. Blood samples will also be drawn through your CVC. The CVC will remain in your body for about 2-5 months.

Study Plans:

If you agree to take part in this study, your doctor will choose one of the following 2 study plans based on the disease and your age and medical history.

Fludarabine/Clofarabine/Busulfan/Rituximab/Total Body Irradiation:

If you are between 1 and 55 years of age and can receive high-dose chemotherapy, or you are between 55 and 65 years old and your doctor agrees, you will receive fludarabine, clofarabine, busulfan, ATG, total body irradiation, and possibly rituximab.

You will receive a test dose of busulfan by vein over 60 minutes as an outpatient. If the test dose cannot be given as an outpatient, you will be admitted to the hospital on Day -10 for intravenous (IV) fluids and will receive the busulfan test dose on Day -9. This low-level "test" dose of busulfan is to check how the level of busulfan in your blood changes over time. This information will be used to decide the next dose needed to reach the target blood level that matches your body size.

About 11 samples of blood will be drawn for pharmacokinetic (PK) testing of busulfan. PK testing measures the amount of study drug in the body at different time points. These blood samples will be drawn at various timepoints starting before the busulfan infusion and continuing over about the next 11 hours. The blood samples will be repeated again with the first day of high-dose busulfan treatment. Each sample will be about 1 teaspoon of blood. A temporary heparin lock will be placed in your vein to lower the number of needle sticks needed for these draws. If it is not possible for the PK tests to be performed for technical or scheduling reasons, you will receive the standard fixed dose of busulfan.

If you will receive the test dose as an outpatient, you will be admitted to the hospital on Day -8 and will receive fluids by vein. If appropriate for the disease, you will receive rituximab by vein over 4-6 hours on Day -8.

If you will receive the test dose as an inpatient, you will be admitted on Day -10 and will receive fluids by vein. If appropriate for the disease, you will receive rituximab by vein over 4-6 hours on Day -10.

On Days -7 through -4, you will receive fludarabine by vein over 1 hour, clofarabine by vein over 1 hour, and busulfan by vein over 3 hours. You will receive ATG on Days -4 and -3. On Day -3, you will receive a single treatment of low-dose total body irradiation. You will "rest" (not receive chemotherapy drugs) on Days -2 and -1. Day 0 is the day of the cord blood transplant, so the negative day numbers are used to label the treatment days before the transplant.

All chemotherapy drugs, fluids, and other drugs that must be given by vein will be infused through the catheter. Once the back-up cells are collected, all participants will be admitted to the hospital as indicated by their assigned treatment plan schedule.

Fludarabine/Melphalan:

If your doctor chooses fludarabine and melphalan, you will have the following schedule:

* On Day -6 (6 days before your transplant), you will be admitted to the hospital and will receive fluids by vein.
* On Days -5, -4, and -3, you will receive fludarabine by vein over 30 minutes.
* On Days -4 and -3, you will receive ATG by vein over 4 hours.
* On Day -2, you will receive fludarabine by vein over 30 minutes and melphalan by vein over 30 minutes.
* On Day -1, you will not receive any drugs.
* On Day 0, you will receive your cord blood transplant through the CVC.

Supportive Drugs:

Starting on Day -3, you will receive mycophenolate mofetil as a tablet by mouth 2 times a day. If you are not able to take the tablet by mouth, you will receive MMF by vein over 2 hours 2 times a day. If you do not have GVHD at Day 100 after your cord blood transplant, the dose of MMF will be gradually lowered. If you have GVHD, MMF may be stopped 7 days after the GVHD is controlled.

Starting on Day -2, you will receive tacrolimus by vein as a continuous (nonstop) infusion until you are able to take it by mouth. You will then take tacrolimus by mouth 2 times a day for about 6 months. After that, your tacrolimus dose may be gradually lowered if you do not have GVHD. Your doctor will discuss this with you.

Starting on Day 0, you will receive filgrastim (G-CSF) through a needle under the skin 1 time a day every day until your white blood count begins to recover. Filgrastim is designed to help cells in the bone marrow to divide, which helps raise white blood cells counts more quickly, lower fever, and decrease the risk of infection.

Study Visits:

At about 1, 3, 6, and 12 months after the transplant:

* You will have a physical exam.
* You will be checked for possible reactions to the transplant and study drugs, including GVHD.
* Blood (about 4 teaspoons) will be drawn for routine tests, to check for CMV antibodies, and for genetic tests to learn if the donor's cells have "taken". The routine blood tests will be repeated as often as the doctor thinks is needed.
* If the doctor thinks it is needed, you will have a bone marrow aspiration to check the status of the disease.

You will need to stay in the hospital for about 4 weeks. After you leave the hospital, you will continue as an outpatient in the hospital area, which means you will have to stay close enough to be able to come back for any visits for about 100 days after the transplant.

Length of Participation:

You will be on study for up to 1 year. You will be taken off study early if the disease gets worse, if intolerable side effects occur, if the cord blood is infected and cannot be transplanted, if you are unable to follow study directions, or if your doctor thinks it is in your best interest.

This is an investigational study. Fucosylation is not an FDA-approved process. It is currently being used for research purposes only. Fludarabine, busulfan, clofarabine, melphalan, mycophenolate mofetil, tacrolimus, and rituximab are FDA approved and commercially available to be given to patients with leukemia or lymphoma having a cord blood transplant. Total body irradiation is delivered using FDA-approved and commercially available methods.

Up to 50 patients will be enrolled in this study. All will be enrolled at MD Anderson.

Cord Blood Fucosylation to Enhance Homing and Engraftment in Patients With Hematologic Malignancies

Engraftment is defined as the evidence of donor derived cells (more than 95%) by chimerism studies in the presence of neutrophil recovery by day 28 post stem cell infusion.

Engraftment date is the first day of three (3) consecutive days that the absolute neutrophil count (ANC) exceeds 0.5 x109/L. Time measured in days.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Myeloablative Haploidentical BMT With Post-transplant Cyclophosphamide for Pediatric Patients With Hematologic Malignancies	NCT02120157	Myeloablative C... HLA-mismatched ... Graft Survival Transplantation...	Cyclophosphamid... TBI Busulfan Unmanipulated B... Tacrolimus Mycophenolate m...	6 Months - 25 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Cord Blood Fucosylation to Enhance Homing and Engraftment in Patients With Hematologic Malignancies	NCT01471067	Blood And Marro... Leukemia Lymphoma Transplantation... Transplantation...	Melphalan Fludarabine Mycophenolate m... Tacrolimus Cord Blood Infu... Rituximab ATG Busulfan Clofarabine Total Body Irra...	1 Year - 80 Years	M.D. Anderson Cancer Center
Cord Blood Fucosylation to Enhance Homing and Engraftment in Patients With Hematologic Malignancies	NCT01471067	Blood And Marro... Leukemia Lymphoma Transplantation... Transplantation...	Melphalan Fludarabine Mycophenolate m... Tacrolimus Cord Blood Infu... Rituximab ATG Busulfan Clofarabine Total Body Irra...	1 Year - 80 Years	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for transplantation, bone marrow