Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Hematologic Neoplasms

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Chronic Graft Versus Host Disease

Acute Graft Versus Host Disease

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Lymphosarcoma

Chronic Myeloproliferative Disorders

Antineoplastic Agents

All Drugs and Chemicals

Altretamine

One cord blood unit will be thawed on day -14 before transplantation and selected using the CliniMACS for primitive cells that express CD133. These cells will be expanded ex vivo for a total of 14 days, using a two-stage procedure. On Day 0 the expanded cells will be harvested, washed three times with CliniMACS buffer (Miltenyi) plus 1% HSA per standard laboratory and clinical practice and the expanded cell product will be infused to a patient who has been prepared with a standard, myeloablative preparative regimen. A second, unexpanded, cord blood product will be infused on Day +1 for safety.

Day 0: the expanded cell product will be infused to patient; Day +1: A second, unexpanded, cord blood product will be infused

Ex vivo expansion of cord blood

Allen R. Chen, MD,PhD. MHS

This study is to evaluate the safety of transplantation of two cord blood products, including toxicities in patients following high-dose, myeloablative chemotherapy for blood malignancies. It is also to determine if the use of two cord products results in an improvement in neutrophil engraftment.

The success of BMT as a curative option for patients with malignancies is frequently limited by the inability to identify an appropriate donor in time for transplantation.

Transplantations utilizing umbilical cord blood stem cells are increasingly successful. Data suggest that there are fewer and less developed T-cells in cord products when compared to bone marrow and so are likely to produce less graft-vs.-host disease (GVHD) even in the mismatched setting. In addition, the grafts are easily available second to the ease of collection as compared with other sources such as bone marrow and peripheral blood stem cells (PBSCs). The ability to build cord blood repositories containing samples with HLA types from minorities has and will continue to increase the likelihood of finding suitable products for under represented minorities such as African-Americans, Hispanic populations and mixed ethnic populations.

Unfortunately, limitations remain, secondary to the time to engraftment when the cell dose is less than optimal, resulting in delayed or failed engraftment. In addition, increased cell dose appears to be associated with disease free survival. Therefore, this modality of transplant is generally limited to smaller patients. This protocol evaluates the infusion and engraftment of two cord blood products - one that has been expanded ex vivo and one that has not been expanded following myeloablative chemotherapy for the treatment of hematological malignancies.

Primary Objective:

-To evaluate the safety of transplantation of two cord products including an expanded unit including infusional toxicities and potential immunologic competition.

Secondary Objective:

-To determine if the use of two cord products results in an improvement in neutrophil engraftment (ANC\>500) in subjects as demonstrated by engraftment \<=21 days.

Tertiary Objectives:

Patients will be compared with patients participating in other trials at our institution and to those who receive therapy as per standard of care.

* To evaluate the rate, extent, and durability of hematopoietic reconstitution and in particular to determine the relative contribution of each cord unit in early engraftment and long-term engraftment
* To estimate the rate and severity of graft-vs-host disease
* To estimate the rates of infectious complications
* To obtain preliminary data regarding disease-free and overall survival
* To collect samples for future studies of immune reconstitution and for future studies in the laboratory regarding disease and the immune system

We will be able to track the fate of both the unmanipulated and expanded CB progenitors by evaluating differences in the cord products and the recipient by evaluation of sex mismatch, HLA type and/or restriction length polymorphisms (RFLPs). If the expanded CB cells are detected in the patients long-term, this will give us confidence to use expanded CB as the sole hematopoietic progenitor cell support, in future studies.

The major risk is non-engraftment of either one or both of the cord blood units. Non-engraftment of one of the units may lead to prolonged cytopenia and a marked increased risk for infection. Failure of either unit to engraft as defined as failure to detect cells from either cord blood product at Day +60 is likely to result in the death of the subject. There is the possibility of failure of long-term engraftment from both cords. This would be fatal unless an alternative donor option was identified or the unlikely event of autologous reconstitution of bone marrow. There is a possibility of an immune competition of both cord blood products . This could result in the loss of the cord product that would have been responsible for long term engraftment. There is a possibility of the expanded cord product to fail release testing. In this event, only the unexpanded cord would be infused and would likely result in delayed engraftment.

As with all cellular products there are risks associated with the infusion including but not limited to anaphylaxis, transfusion reaction, hemolysis, side-effects of the DMSO that the product is stored in (bradycardia, hypothermia, neurologic changes). The expanded product will be washed however there remains a small chance that a small amount of growth factor remains. The risk associated with these will be allergic.

Busulfan toxicity

1. Nausea and vomiting
2. Myeloablation
3. Pulmonary complications
4. Seizures
5. Other toxic effects which may be produced by Busulfan erythematous skin rash, hyperpigmentation, hepatic dysfunction, amenorrhea, testicular atrophy, gynecomastia, myasthenia symptoms, cataract and atrophic bronchitis associated with cytologic dysplasia.

Cyclophosphamide Toxicity

1. Leukopenia, anemia
2. Alopecia
3. Nausea, vomiting, increased AST, ALT, mucositis, diarrhea
4. Headache, dizziness
5. Cardiac necrosis rarely with high dose cyclophosphamide
6. Hemorrhagic cystitis, SIADH
7. Teratogenic, may cause secondary neoplasms, anaphylaxis (rare)
8. Fluid retention.
9. Cardiomyopathy.
10. Hemorrhagic Cystitis.

At the doses used for uroprotection mesna is virtually non-toxic. However, adverse effects which may be attributable to mesna include nausea and vomiting, diarrhea, abdominal pain, altered taste, rash, urticaria, headache, joint or limb pain, hypotension and fatigue.

Total Body Irradiation Toxicity:

1. Nausea and Vomiting
2. Alopecia
3. Parotitis and Pancreatitis
4. Diarrhea
5. Fever
6. Erythema
7. Hyperpigmentation
8. Mucositis
9. Late Effects - cataract formation, growth retardation, carcinogenesis and the probability of sterilization.

Transplantation of Umbilical Cord Blood Following Chemotherapy for Blood Cancers

Transplantation of Expanded and Unexpanded Umbilical Cord Blood Units Following Myeloablative Chemotherapy for Hematologic Malignancies

Number of participants who reached 3 consecutive days with ANC \> 500

Number of participants who died without relapse in less than 100 days.

Children's Cancer Foundation

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Neutrophil count was followed based on regular lab assessments

Patients with a hematologic malignancy who are candidates for myeloablative allogeneic BMT but lack an available matched sibling or unrelated marrow donor are eligible for this study if they have two suitably matched cord blood products with an adequate (1 x 10e7 TNC/kg IBW) but suboptimal (\<5 x 10e7 TNC/kg IBW) cell dose.

One cord blood unit is expanded beginning 14 days before graft infusion (6 or 7 days before the start of the preparative regimen). Patients receive a standard myeloablative preparative regimen. The expanded cord blood unit is infused on day 0 and the unmanipulated cord blood unit is expanded on day 1.

Single Arm

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Allen Chen, MD,PhD,MHS

Ex vivo expansion of cord blood: Day 0: the expanded cell product will be infused to patient; Day +1: A second, unexpanded, cord blood product will be infused

Receive Two Cord Blood Units

Number of Participants With Toxicities Related to Infusion of Expanded Cord Blood Products

Neutrophil Engraftment Within 21 Days

Non-relapse Mortality

Patients with a hematologic malignancy who are candidates for myeloablative allogeneic BMT but lack an available matched sibling or unrelated marrow donor are eligible for this study if they have two suitably matched cord blood products with an adequate (1 x 10e7 TNC/kg IBW) but suboptimal (\<5 x 10e7 TNC/kg IBW) cell dose. Eligible diagnoses include AML, MDS, ALL after failure of at least one regimen, mixed lineage leukemia, CML beyond first chronic phase, and lymphoma ineligible for autologous transplantation.

Overall Study

Antirheumatic Agents

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

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

Syndrome

Preleukemia

Myelodysplastic Syndromes

Myeloablative preparative regimen of chemotherapy and radiation followed by double unit umbilical cord blood transplantation

Cord blood transplantation

Juliet Barker, MBBS

The hypothesis of the study is double unit umbilical cord blood transplantation in adults will be associated with a one year survival rate of at least 40%.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Transplantation of Umbilical Cord Blood Following Chemotherapy for Blood Cancers	NCT00539656	Acute Myeloid L... Leukemia, Lymph... Leukemia, Bilin... Leukemia, Myelo...	Ex vivo expansi...	6 Months - 55 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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
Adult Double Cord Blood Transplant Study	NCT00514579	Cord Blood Stem... Hematologic Mal...	Cord blood tran...	22 Years - 50 Years	Center for International Blood and Marrow Transplant Research
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
Adult Double Cord Blood Transplant Study	NCT00514579	Cord Blood Stem... Hematologic Mal...	Cord blood tran...	22 Years - 50 Years	Center for International Blood and Marrow Transplant Research

Spots Global Cancer Trial Database for cord blood stem cell transplantation