Neoplasms

Blood and Lymph Conditions

All Conditions

Hematologic Neoplasms

Hematologic Diseases

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Busulfan

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Busulfan,Cyclophosphamide, Fludarabine, Cord Blood Stem Cell Infusion

Busulfan dosing will be as follows: Patients \< 12 kg: 1.1 mg/kg/dose IV every 6 hours for 16 doses total; patients \> 12 kg: 0.8 mg/kg/dose IV every 6 hours for 16 doses. It will be given on Days -9, -8, -7 and -6.

Cyclophosphamide (50 mg/kg/dose) will be given IV on Days -5, - 4, -3, and -2 over 1 hour. The total dose to be given over 4 days is 200 mg/kg.

Fludarabine will be given IV daily over 1 hour for 3 days. Dosing will be as follows: for patients ≤ 10 kg: 1.3 mg/kg; for patients \> 10 kg: 40 mg/m\^2.

The cord blood stem cells will be infused on Day 0.

Cord Blood Stem Cell Infusion

Caridad A Martinez, MD

Robert A Krance, MD

In this study, the investigators will use busulfan and cyclophosphamide (BuCy) backbone with the addition of fludarabine as the preparative Stem Cell Transplant (SCT) regimen. As an attempt to improve engraftment rate and reduce infections, the investigators are going to incorporate fludarabine in the conditioning regimen. The use of a BuCy backbone has been widely used and comparable to total body irradiation and cyclophosphamide (Cy/TBI) regimen.

Encouraging data on adding fludarabine to the SCT regimen have been reported. A fludarabine-based, conditioning regimen, with adequate immunosuppressive activity could conceivably allow engraftment of stem cells from alternative donors in hematologic malignancies patients with acceptable engraftment rates and low transplant-related mortality. Regimen-related toxicity is believed to be a major contributing factor to GVHD. Therefore this approach may also lead to reduced GVHD, as some investigators have suggested.

In an attempt to decrease the rate of viral infection and reactivation, the investigators will avoid ATG (Thymoglobulin) / Campath (anti-CD52), and instead administer Mycophenolate Mofetil (MMF). The addition of fludarabine should compensate any increase risk of graft failure with the removal of the ATG/Campath. The investigators anticipate that the removal of ATG/Campath will facilitate immune reconstitution more efficiently after receiving a UCBT.

The following will be given as the conditioning regimen for the transplant:

BUSULFAN: Busulfan (intravenous BUSULFEX) dosing will be as follows: patients \<12 kg: 1.1 mg/kg/dose IV every 6 hours for 16 doses total; patients \>12 kg: 0.8 mg/kg/dose IV every 6 hours for 16 doses. Administration and pharmacokinetic monitoring will be performed as per standard practice. Anticonvulsants will be given in accordance with standard Blood and Marrow Transplant Program recommendations.

CYCLOPHOSPHAMIDE: Cyclophosphamide (50 mg/kg/dose) will be given IV on Days -5, - 4, -3, and -2 over 1 hour. The total dose to be given over 4 days is 200 mg/kg. Mesna will be given in accordance with standard Blood and Marrow Transplant.

FLUDARABINE: Fludarabine will be given IV daily over 1 hour for 3 days. Dosing will be as follows: for patients ≤ 10 kg: 1.3 mg/kg; for patients \> 10 kg: 40 mg/m2. Preparation, administration and monitoring will be according to standard practice procedure

POST-TRANSPLANT IMMUNOSUPPRESSION:

* CSA will begin on Day -3. For children \< 40 kg, the initial dose will be 2.5 mg/kg IV over 2 hours every 12 hours. Dose adjustments will be made to maintain levels above 200 ng/mL. Levels will be done on Day 0 and then as clinical indicated. CSA will be tapered per institutional SOP. Once the patient can tolerate oral medications and has a normal gastrointestinal transit time, CSA will be converted to an oral form.
* MMF will begin on Day 0 at a dose of 15 mg/Kg IV or orally TID, and will be discontinued on Day +45 unless GVHD is present.

CNS Disease: Patients with CNS relapse or primary CNS disease that is symptomatic or associated to radiological changes will receive additional irradiation to the craniospinal axis.

SUPPORTIVE CARE:

* Supportive care will be provided as per standard practice of the Blood and Marrow Stem Cell Transplant program at the Texas Children's Hospital, including all prophylactic and therapeutic clinical care issues. These practices may be modified if necessary for any individual patient in order to provide optimum care for that particular patient.
* IVIG: Intravenous immunoglobulin (500 mg/kg per dose) will be given monthly until discontinuation of GVHD therapy and documentation of antibody production.
* CB-CTLs: Patients enrolled in this protocol may also be eligible for infusion of CB-derived multivirus-specific CTL to provide virus-specific immune reconstitution and treatment of viral infections after CBT.

EVALUATIONS DURING THE STUDY:

Screening Procedures; Pre-HCT:

* Physical examination
* Pregnancy test
* Complete blood count and chemistries
* Electrocardiogram
* Echocardiograph
* PT/PTT/Fibrinogen/Anti-Thrombin III/von Willebrand Factor
* Viral tests
* Bone marrow aspirate and biopsy/Lumbar puncture
* Renal Function (GFR)
* Lumbar puncture will be performed
* Pulmonary Function test

EVALUATIONS BETWEEN DAY 0 AND DAY 100:

* Physical examination
* Complete blood count and chemistries
* Lytes/BUN/Cr
* Peripheral blood for STRs or FISH analysis for molecular diagnostics
* Lymphocyte phenotype testing and lymphoproliferative responses
* Bone marrow aspirate and biopsy for assessment of leukemia status and UCB engraftment
* Lumbar puncture
* Immunoglobulins

EVALUATIONS AFTER DAY 100:

* Physical examination
* Complete blood count and chemistries
* Lytes/BUN/Cr
* Serum chemistries
* Peripheral blood with assessment of engraftment by STRs or FISH analysis and enzyme levels
* Echocardiograph with LVEF
* Bone marrow aspirate and biopsy assessment of leukemia status and UCB engraftment
* Lymphocyte phenotype testing (CD3, CD4, CD8, CD19 and CD56) and lymphoproliferative responses
* Immunoglobulins

FOLLOW-UP INTERVAL:

Patients will be seen in the hospital everyday until discharge. After discharge from the hospital, the patient will be following on the BMT clinics on a regular basis as recommended by the primary physician.

Umbilical Cord Blood Transplant for Children With Myeloid Hematological Malignancies

Umbilical Cord Blood Transplant for Children With Myeloid Hematological Malignancies (UCAML)

To determine the overall survival rate at 1 year after umbilical cord blood transplant in pediatric patients with myeloid hematological malignancies.

Number of participants with acute GVHD graded by the method of Przepiorka et al, which evaluates skin involvement, lower and upper GI, and liver function (bilirubin), each being graded in stages from 0 to 4, where 0 means no acute GVHD, and 4 is the highest stage of acute GVHD.

Number of participants with chronic GVHD graded by the method of Przepiorka et al, which evaluates skin, joints, oral, ocular, hepatic, esophagus, GI, respiratory, platelet, and musculoskeletal involvement, in stages from 0 to 3.

To assess relapse rate at 1 and 3 years after transplant. Cumulative incidence of relapse was calculated from the date of umbilical cord blood transplant using the competing risk method as described in Gray(1988) with death prior to relapse as the competing risk. Participants still alive without a date of relapse were censored at the time of the last follow-up.

To evaluate donor engraftment at 100 days, 6, 9, 12, 24, and 36 months after transplant.

Achievement of untransfused platelet count \> 20 x 10\^9/L on three consecutive days

Achievement of absolute neutrophil count \> 0.5 x 10\^9/L on three consecutive days

Center for Cell and Gene Therapy, Baylor College of Medicine

Baylor College of Medicine

Assistant Professor, Pediatric Hematology/Oncology, Center for Cell and Gene Therapy

The analysis included all participants who enrolled in the study and underwent umbilical cord blood transplant (UCBT).

Busulfan,Cyclophosphamide, Fludarabine, Cord Blood Stem Cell Infusion

Busulfan: Busulfan dosing will be as follows: Patients \< 12 kg: 1.1 mg/kg/dose IV every 6 hours for 16 doses total; patients \> 12 kg: 0.8 mg/kg/dose IV every 6 hours for 16 doses. It will be given on Days -9, -8, -7 and -6.

Cyclophosphamide: Cyclophosphamide (50 mg/kg/dose) will be given IV on Days -5, - 4, -3, and -2 over 1 hour. The total dose to be given over 4 days is 200 mg/kg.

Fludarabine: Fludarabine will be given IV daily over 1 hour for 3 days. Dosing will be as follows: for patients ≤ 10 kg: 1.3 mg/kg; for patients \> 10 kg: 40 mg/m\^2.

Cord Blood Stem Cell Infusion: The cord blood stem cells will be infused on Day 0.

Umbilical Cord Blood Transplant

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Caridad A. Martinez

100 days

1-Year

3-Year

The analysis included all participants who enrolled in the study and underwent umbilical cord blood transplant (UCBT) except the one participant who died 4 days after transplant.

Overall Survival at 100 Days, 1 Year, and 3 Years After Umbilical Cord Blood Transplant in Pediatric Patients.

The analysis included all participants who underwent Umbilical Cord Blood Transplant (UCBT) and were evaluable for acute GVHD. A participant was evaluable for acute GVHD if he/she engrafted and either completed 100 days observation after transplant or experienced acute GVHD.

Number of Participants With Severe Acute GVHD Grade III-IV

The analysis included all enrolled participants who underwent umbilical cord blood transplant (UCBT) and were evaluable for chronic GVHD. A participant was evaluable for chronic GVHD if he/she engrafted and survived or remained in the study for more than 100 days after transplant. However, if the participant(s) relapsed within or around 100 days, they would not be evaluable.

Number of Participants With Chronic GvHD

1 year

3 year

Number of Participants With Relapse Rate After Transplant

6 months

9 months

12 months

24 months

36 months

The analysis included all participants who underwent umbilical cord blood transplant (UCBT) except the one participant who died 4 days after transplant. If the participant(s) relapsed, they would not be evaluable for donor engraftment.

Number of Participants With Donor Engraftment After Transplant.

Number of Participants With Platelet Engraftment

Number of Participants With Neutrophil Engraftment

Overall Study

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Anticonvulsants

Nootropic Agents

Analgesics

Levetiracetam

Interleukin-2

Allopurinol

Mesna

Antimetabolites

Analgesics, Non-Narcotic

Enzyme Inhibitors

Antioxidants

Protective Agents

Patients with chemotherapy refractory Acute Myelogenous Leukemia (AML) after a double T-cell depleted (TCD) umbilical cord blood (UCB) transplantation where the smaller unit is activated overnight in interleukin-2 (IL-2). IL-2 will be given three times weekly for 6 doses beginning on days+3 and days +60 to expand UCB-derived natural killer (NK) cells in vivo.

On Day 8 pre-transplant, start hydration with allopurinol per standard of care.

On Days 7, 6 and 5 pre-transplant, 25 mg/m\^2 intravenously over 1 hour.

On Days 5, 4, 3, and 2 pre-transplant, 165 cGy times 2 (330 cGy daily, 1320 total dose) according to the University Of Minnesota Blood and Marrow Transplant Program total body irradiation (TBI) guidelines.

Total body irradiation

On Days 7 and 6 pre-transplant, 60 mg/kg intravenously (IV) over 2 hours with a high volume fluid flush and mesna per institutional guidelines.

Alternate Preparative Therapy For Patients Not Able To Receive TBI: Days 5, 4, 3 and 2 pre-transplant; 50 mg/kg/day IV over 2 hours.

Alternate Preparative Therapy for Patients Not Able to Receive Total Body Irradiation (TBI): Hydration therapy on Day 10 pre-transplant.

Alternate Preparative Therapy For Patients Not Able To Receive TBI: Days 9, 8, 7 and 6 pre-transplant; 0.8 mg/kg (1.1 mg/kg if \<12 kg) intravenously every 6 hours

Day 0: Two UCB units will compose the graft. The infusion of the first UCB unit should begin within 15 minutes, and no later than 30 minutes after arrival on the Unit. The UCB unit without IL-2 activation will be infused first, followed by the IL-2 activated unit. Both cords will be infused within 30-60 minutes of each other as deemed clinically safe by the BMT attending.

Umbilical Cord Blood Transplantation

First Course of IL-2 (begin day +3) post-transplant: For patients ≥ 45 kg, IL-2 will be given at 9 million units every other day for a total of 6 doses subcutaneously. Patients weighing less than 45 kilograms, the IL-2 will be dosed at 5 million units/m\^2 every other day for a total of 6 doses.

Second Course of IL-2 (day +60):

Patients will receive a second course of IL-2 beginning on Day +60 post transplant to expand and educate the NK cells derived from the UCB graft source.

Michael Verneris, M.D.

This trial is proposes to build on our experience and is designed to maximize early (day 3-14) and late (day 60-71) donor-derived natural killer (NK) cell expansion and function in vivo. The proposed platform will allow us the unique opportunity to compare in vivo function from a transplanted umbilical cord blood (UCB) source (presumed to contain NK progenitors requiring "education" in the recipient).

This single center study will determine the feasibility and safety of using a myeloablative conditioning regimen followed (on day 0) by transplantation with double T-cell depleted (TCD) umbilical cord blood (UCB) units where the unit with fewer mononuclear cells (MNCs)/kg will be selected for overnight IL-2 activation prior to infusion. Beginning on day +3, post transplant IL-2 will be administered thrice weekly, not on consecutive days, for a total of 6 doses to expand UCB derived progenitor cells. Post transplant immune suppression prophylaxis will not be administered with the intent to lessen toxicity and allow allogeneic NK cells to function longer providing better anti-leukemic therapy. However if either UCB unit has more than 5% T-cells, the patient will not receive either course of IL-2. Beginning on day +60 after transplantation, a second course of IL-2 will be administered thrice weekly, not on consecutive days, for a total of 6 doses with the purpose of enhancing the in vivo expansion and education of NK cells derived from engrafting UCB cells.

T-Cell Depleted Double UCB for Refractory AML

T-Cell Depleted Double UCB With Post Transplant IL-2 for Refractory Myeloid Leukemia

The primary endpoint is a disease free survival at 3 months in patients with chemotherapy refractory AML after a double T-cell depleted (TCD) umbilical cord blood (UCB) transplantation where one TCD unit is activated overnight in IL-2 followed by the administration of two courses of IL-2 three times a week for 6 doses beginning on day +3 and on day +60 to expand UCB-derived NK cells in vivo.

Incidence of graft failure defined as an absolute neutrophil count of less than 500/uL and a bone marrow that is less than 5% cellular (marrow aplasia)

Defined as leukemia clearance and complete remission. Patients will be followed for disease response for 1 year from transplantation unless: consent is withdrawal, patient is unevaluable - if a patient is not evaluable, follow only until the resolution or stabilization of treatment related toxicity, new anti-cancer treatment is started, patient is discharged to hospice (terminal) care.

Defined as leukemia clearance and complete remission. Patients will be followed for disease response for 2 years from transplantation unless: consent is withdrawal, patient is unevaluable - if a patient is not evaluable, follow only untilthe resolution or stabilization of treatment related toxicity, new anti-cancer treatment is started, patient is discharged to hospice (terminal) care.

Masonic Cancer Center, University of Minnesota

Allopurinol: start on Day -8 per institutional guidelines Fludarabine: give on Days -7, -6 and -5, 25 mg/m\^2 intravenously (IV) Cyclophosphamide: give on Days -7 and -6, 60 mg/kg IV along with mesna per institutional guidelines Total body irradiation: give on Days -5, -4, -3, and -2, 165 cGy twice daily Double T-cell depleted umbilical cord blood transplantation with activation of one of the units in interleukin-2 (IL-2): give on Day 0 IL-2: start on Day +3 and Day +60, 9 MU subcutaneously three times weekly for 6 doses

Alternate preparative therapy for patients not able to receive additional radiation

Levetiracetam (Keppra): begin on Day -10 per institutional guidelines Busulfan: give Day -9 through Day -6, 0.8 mg/kg (1.1 mg/kg if \<12 kg) IV every 6 hours Cyclophosphamide: give Day -5 through Day -2, 50 mg/kg/day IV along with mesna per institutional guidelines

Patients With Acute Myelogenous Leukemia

Age, Categorical

United States

Region of Enrollment

Michael R Verneris

Disease Free Survival

Incidence of Graft Failure

Incidence of Acute Graft-Versus-Host Disease

Transplant-Related Mortality

Clinical Disease Response

Duration of Survival

Cytoxan, Fludarabine, Total Body Irradiation (TBI), Cord Blood Stem Cell Infusion

50 mg/kg/dose will be given IV on day -5,-4, -3, -2 over 1 hour. The total dose to be given over 4 days is 200 mg/kg.

Cytoxan

40mg/m2/day will be given IV over 1 hour on day -4, -3, -2

1.75Gy/fraction will be given on day -9, -8, -7, -6

Total Body Irradiation (TBI)

The cord blood stem cells will be infused on day 0

The purpose of this study is to determine the safety and effectiveness of UCBT to treat patients with lymphoid hematological diseases and to see if this treatment can decrease the incidence of leukemia relapse, GVHD and infections.

These patients have a type of blood cell disorder that is very hard to cure. This treatment that is being used in this trial is known as a stem cell transplant. This treatment might help the patient live longer without the disease. It uses much stronger doses of drugs and radiation to kill the diseased cells that could be given without the transplant. We also think that the healthy cells from the donor may help fight any diseased cells left after the transplant.

For the transplant to take place, we will administer stem cells from a 'donor' whose cells best 'match' the patient's. In this study umbilical cords will be the source of the stem cells. Before the transplant, two very strong drugs plus total body irradiation will be given to as preconditioning. This treatment will kill most of your blood-forming cells in the bone marrow. The patient will then get then healthy stem cells.

If the patient has the disease in the central nervous system (CNS), they will receive radiation to the head and spine before starting the conditioning. This is to try to get disease control in the CNS. Radiation will not be given for children under 2 yrs old.

Currently, many umbilical cord blood units are available in public banks for transplantation in patients lacking bone marrow donors. UCB transplants (UCBT) may offer several advantages over adult bone marrow or peripheral blood stem cell transplants, including:

1. rapid availability,
2. absence of donor risk,
3. low risk of transmissible infectious diseases,
4. low risk of acute GvHD (Graft vs. Host Disease)

The three main causes of death after umbilical cord blood transplantation for these kind of disorders are graft failure, infection and disease relapse.

In this study we are trying to address these three problems:

To help improve engraftment we will add the drug Fludarabine to Cytoxan and total body irradiation. Fludarabine is a very strong medicine. We will try to decrease infections and reduce leukemia relapse by using fludarabine instead of antithymocyte globulin (ATG).

After the eligible criterion for treatment has been met and a suitable UCB stem donor has been found, the patient will have a central line placed.

Research Therapy:

After placement of the central line, the following chemotherapy will be given to after admission to the hospital and before the infusion of the umbilical cord blood stem cells:

* 9 - 6 days before the infusion: Total Body Irradiation (TBI) in two fractions ("doses") per days.
* 5 - 2 days before the infusion: Cytoxan given daily for 4 days, over 1 hour as an intravenous infusion. Mesna will be given per standards. Mesna is a drug given to decrease the side effects of Cytoxan. It will be given daily as an intravenous infusion while the patient receives the Cytoxan.
* 4 - 2 days before the infusion: Fludarabine given daily for 3 days over 1 hour as an intravenous infusion.

Stem cell transplant (intravenous infusion of the UCB stem cells) - defined as day 0 of the treatment. All other "numbered" days relate to this infusion date. For example, Day 1 is the first day after the stem cell transplant.

The following medications will be given to help decrease side effects from the chemotherapy and UCB infusion: Cyclosporine A (CSA) will be given starting 3 days prior to the stem cell infusion. It will be given daily over 2 hours every 12 hours, after the infusion and then tapered if no GVHD is present.

Administration of Mycophenolate mofetil (MMF) will start on the day the stem cell infusion is completed and will continue daily for 45 days, unless the patient develops GvHD.

Intravenous immunoglobulin's (IVIG) will be given monthly until GVHD therapy is stopped and there is evidence that the patient's body is producing antibodies.

Study Evaluations: Various study evaluations will be performed before and during the trial.

Follow Up: After year 1, the patient will be asked to return to the clinic once a year for consultations and bone marrow tests. A follow up bone marrow biopsy and aspirate will be done 1 and 2 years after transplant. Consultations with specialists will be similar to the ones the patient had before the transplant.

Umbilical Cord Blood Transplant for Children With Lymphoid Hematological Malignancies

Umbilical Cord Blood Transplant for Children With Lymphoid Hematological Malignancies (UCALL)

To determine the survival rate at 1 year after umbilical cord blood transplant in pediatric patients with lymphoid hematological malignancies

To assess platelet recovery at day 42 post transplant

To estimate the risk of severe grade III-IV acute GvHD at day 100.

To estimate the risk of chronic GvHD at 1 year

To assess relapse rate at 1 and 3 years after transplant.

To assess neutrophil count recovery at day 42 post transplant

To evaluate T/B/NK cell recovery and function at day 100, 6, 12, and 24 months after transplant.

To assess leukemia free survival at 1 and 3 years.

Symptoms and General Pathology

Immune System Diseases

Syndrome

Preleukemia

Myelodysplastic Syndromes

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Bone Marrow Diseases

Myeloproliferative Disorders

Chronic Disease

Disease Attributes

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Graft Versus Host Disease

Lymphosarcoma

Chronic Myeloid Leukemia

Chronic Myeloproliferative Disorders

Cord Blood Transplant

Nicole Stephens, RN, BSN, OCN

Juli Murphy, CCRC

Scott Bearman, MD

Robert Rifkin, MD

Mark Brunvand, MD

Jeffrey Matous, MD

Michael Maris, MD

Peter McSweeney, MD

The purpose of this study is to evaluate the incidence of neutrophil engraftment after transplantation of one or two cord blood units meeting a predetermined total minimum cell dose of 2.0 x 10 to the seventh total nucleated cell (TNC)/kg.

This is a non-randomized, phase II protocol to evaluate engraftment of cord blood after treatment with myeloablative conditioning of fludarabine, total body irradiation and cyclophosphamide. All patients will receive tacrolimus and mycophenolate mofetil as prophylaxis for graft-vs-host disease.

Conditioning Regimen:

* Days -10 to -7: Fludarabine 30mg/m2/day IV
* Days -7 to -4: TBI 165 centigray BID
* Days -3 to -2: Cyclophosphamide 40mg/kg/day IV

Day 0: Infusion of Cord Blood Cells

Graft-vs-Host Disease Prophylaxis

* Day -1: Start tacrolimus 0.03mg/kg/day IV
* Day 0: Start MMF 7.5mg/kg IV BID

Treatment of Hematologic Malignancies With Single-Unit or Double-Unit Cord Blood Transplantation

Treatment of Hematologic Malignancies With High-Dose Chemo-Radiotherapy Followed by Single-Unit or Double-Unit Cord Blood Transplantation: A Phase II Study

Colorado Blood Cancer Institute

Melphalan

Patients aged 2-45 years (excluding AML, JMML and MDS patients aged \<16 years) will receive an umbilical cord blood transplant using a myeloablative conditioning regimen comprising:

Fludarabine 25mg/m\^2/day day -8 to -6 (total 75mg/m\^2) Cyclophosphamide 60mg/kg day -7 and -6 (total 120mg/kg) Total body irradiation 13 - 14.4Gy in 6-8 fractions

Patients aged \< 2 years and AML, JMML and MDS patients \<16 years will receive an umbilical cord blood transplant using a myeloablative conditioning regimen comprising:

Busulfan 3.2mg/kg/day in 2 or 4 doses per day, days -9 to -6 (total 12.8mg/kg). Cyclophosphamide 60mg/kg days -4 and -3 (total 120mg/kg) Melphalan 140mg/m\^2 day -2

Rachael Hough

This trial is looking at using umbilical cord blood from unrelated donors after high dose chemotherapy. It is for people who have cancer of the bone marrow or lymphatic system including leukaemia and lymphoma, or a blood disorder called myelodysplastic syndrome (MDS).

The trial is for babies over 4 weeks old, children, and adults up to the age of 45.

During treatment for cancers of the bone marrow or lymphatic system, a lot of the stem cells are damaged and you may need a bone marrow or stem cell transplant to replace them.

Stem cells can also be collected from the umbilical cord of newborn babies. Many people around the world have donated their baby's umbilical cords which are stored safely.

There are usually enough cells in one cord to transplant a small child, but there may not be enough cells for an older child or adult. Researchers want to see if adults and children can safely have stem cells from more than 1 umbilical cord.

Before a transplant, you have high doses of chemotherapy, sometimes with radiotherapy. This intensive conditioning aims to destroy all the cells in your bone marrow, and is called myeloablative conditioning.

The aim of this trial is to see if a transplant using cord blood cells from unrelated donors after myeloablative conditioning is safe, and whether it helps people who need a stem cell transplant but don't have a stem cell donor.

You may be able to enter this trial if you:

* Have leukaemia, lymphoma or another disorder of the bone marrow and treatment with intensive conditioning followed by a stem cell transplant is likely to help you
* Do not have a suitable stem cell donor in your family, and your doctors have not been able to find a matched unrelated donor
* Have satisfactory blood test results
* Are between 4 weeks and 45 years old

You cannot enter this trial if you:

* Have a family member who could donate stem cells to you, or you have a matched unrelated donor
* Can have any other treatment that your doctors think will cure your disease or keep it under control for a long time
* Have already had a lot of radiotherapy (the trial doctor can advise you about this)
* Have already had a bone marrow or stem cell transplant using your own cells
* Have chronic myeloid leukaemia that is in chronic phase and is responding to imatinib, or is in blast phase and is not responding to treatment Have acute lymphoblastic leukaemia that is not responding to treatment or has come back and more than 5% of your bone marrow is made up of immature cells (blasts)
* Have acute myeloid leukaemia that is not responding to treatment or has come back and more than 20% of your bone marrow is made up of immature cells (blasts)
* Have a disease that has come back and you are having another type of treatment (salvage treatment) but your disease is not responding or is getting worse
* Have a blood disorder called myelofibrosis
* Have a blood disorder called aplastic anaemia
* Have an infection that cannot be controlled with medication
* Have either the HIV or HTLV virus
* Are pregnant or breastfeeding

This phase 2 trial aims to recruit 60 people. It will include both adults and children. Everybody taking part will have intensive conditioning before having a transplant of stem cells from the umbilical cord blood of at least 1 unrelated donor.

To take part in this trial, the researchers need to be sure that there are 2 lots of cord blood cells that would be suitable for you. They will only use cells from 2 cords if there is some concern that they won't get enough cells from 1 umbilical cord.

People aged between 2 and 45 (apart from children under the age of 16 who have acute myeloid leukaemia, juvenile myelomonocytic leukaemia (JMML) or MDS) will have conditioning with fludarabine, cyclophosphamide and radiotherapy to the whole body (total body irradiation). This takes 9 days all together. On the last day, you have the stem cells through a drip into a vein.

Children under 2 years of age (and children up to the age of 16 who have acute myeloid leukaemia, JMML or MDS) will have conditioning with busulfan, cyclophosphamide and melphalan. They do not have radiotherapy. This conditioning takes 10 days all together. They have the stem cells through a drip into a vein on the 11th day.

The stem cells find their way into your bone marrow where they will start making new blood cells.

You will see the trial team and have some tests before you start treatment. The tests include:

* Physical examination
* Blood tests
* Chest X-ray
* Lung function tests
* Heart trace (ECG)
* Heart ultrasound (echocardiogram) or MUGA scan
* Bone marrow test When you have your treatment, you will be in hospital for about 4 to 6 weeks. As you will be at a high risk of infection, you will be in your own room. This is called being in isolation. You have another bone marrow test a month after your transplant.

When you go home, you have to go back to the hospital for regular blood tests. This is likely to be 2 or 3 times a week to begin with. You may have to go back into hospital for a few days at some point.

After a transplant, you will see the doctors and have blood tests At least once a week for the first 3 months At least once a month for the rest of the first year The trial doctors will follow your progress closely for at least 2 years.

The main side effect of the treatment you have just before the transplant is a drop in the number of blood cells, causing an increased risk of infection, tiredness and breathing problems.

We have more information about fludarabine, cyclophosphamide, busulfan and melphalan in our cancer drugs section.

It takes longer for blood cells to start growing again after a transplant of cord blood than after other types of stem cell transplant. Even when your blood count gets back to normal, your immune system may take up to 2 years to recover fully.

Unfortunately, this treatment can affect your ability to have children (your fertility). Men taking part will be offered the option to store sperm (sperm banking) before starting treatment. Preserving fertility for women is more complicated and it is important that women talk to their doctors about this before starting treatment.

After any type of bone marrow or stem cell transplant, there is a risk of graft versus host disease (GVHD). This happens when the new stem cells attack your body tissue. It mainly affects your skin, gut and liver.

Rarely, the new stem cells fail to start working. This is more common with cord blood transplants than with other bone marrow transplants. And even if your transplant is successful, there is a risk your disease may come back. Because of these risks, your doctors will monitor you very closely after your transplant.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Umbilical Cord Blood Transplant for Children With Myeloid Hematological Malignancies	NCT01247701	Myeloid Hematol...	Busulfan Cyclophosphamid... Fludarabine Cord Blood Stem...	- 17 Years	Baylor College of Medicine
T-Cell Depleted Double UCB for Refractory AML	NCT01464359	Acute Myelogeno... Refractory Acut...	Allopurinol Fludarabine Total body irra... Cyclophosphamid... Levetiracetam Busulfan Umbilical Cord ... Interleukin-2	2 Years - 45 Years	Masonic Cancer Center, University of Minnesota
Umbilical Cord Blood Transplant for Children With Myeloid Hematological Malignancies	NCT01247701	Myeloid Hematol...	Busulfan Cyclophosphamid... Fludarabine Cord Blood Stem...	- 17 Years	Baylor College of Medicine
Umbilical Cord Blood Transplant for Children With Lymphoid Hematological Malignancies	NCT01247688	Lymphoid Hemato... Umbilical Cord ...	Cytoxan Fludarabine Total Body Irra... Cord Blood Stem...	-	Baylor College of Medicine
Treatment of Hematologic Malignancies With Single-Unit or Double-Unit Cord Blood Transplantation	NCT00328237	Acute Myeloid L... Acute Lymphobla... Chronic Myeloid... Non-Hodgkin Lym... Myelodysplastic...	Cord Blood Tran...	18 Years - 49 Years	Colorado Blood Cancer Institute
Myloablative Cord Blood Transplant in Haematological Malignancies (MAC UCBT)	NCT02310997	Leukaemia Lymphoma Other Haematolo...	Umbilical Cord ... Cyclophosphamid... Total body irra... Busulfan Melphalan Fludarabine	28 Days - 45 Years	University College, London

Spots Global Cancer Trial Database for umbilical cord blood transplant