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

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.

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
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

Spots Global Cancer Trial Database for cord blood stem cell infusion