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

Preleukemia

Myelodysplastic Syndromes

Syndrome

Precancerous Conditions

Antirheumatic Agents

Cyclophosphamide

Busulfan

Thiotepa

Antilymphocyte Serum

Alpha Beta Total Body Irradiation - TBI first Day Treatment

* 11 Anti-thymocyte globulin (ATG)
* 10 ATG
* 9 ATG
* 8 TBI
* 7 TBI
* 6 TBI
* 5 Thiotepa
* 4 Thiotepa
* 3 Cyclophosphamide
* 2 Cyclophosphamide
* 1 Rest 0 Transplant with alpha beta T cell depleted stem cells

Alpha Beta Total Body Irradiation - TBI last Day Treatment

* 9 ATG
* 8 ATG
* 7 Thiotepa + ATG
* 6 Thiotepa
* 5 Cyclophosphamide
* 4 Cyclophosphamide
* 3 TBI
* 2 TBI
* 1 TBI 0 Transplant with alpha beta T cell depleted stem cells

Alpha Beta Non-irradiation regimen Day Treatment

* 9 Busulfan + ATG
* 8 Busulfan + ATG
* 7 Busulfan +ATG
* 6 Busulfan
* 5 Thiotepa
* 4 Thiotepa
* 3 Cyclophosphamide
* 2 Cyclophosphamide
* 1 0 Transplant with alpha beta T cell depleted stem cells

Alpha Beta T cell depletion

Patricia Hankins, BSN, RN, CCRC

Meghan Rys, MS, CCRP

Nancy J Bunin, MD

Stephan A Grupp, MD, PhD

This is a single arm pilot study for patients using α/β T cell-depleted peripheral Stem Cell Transplantation (PSCT) in with alternative donor sources with hematologic malignancies receiving alternative donor (unrelated or partially matched related) mobilized peripheral stem cells (PSCs) using the CliniMACS system for T cell depletion plus CD19+ B cell depletion to determine efficacy as determined by engraftment and graft versus host disease (GVHD), and one year leukemia free survival.

intervention with device: Alpha Beta T cell depletion

Allogeneic Stem Cell Transplant With Alpha/Beta T AND B Cell Depletion for Hematologic Malignancies

UNRELATED AND PARTIALLY MATCHED RELATED DONOR PERIPHERAL STEM CELL TRANSPLANTATION WITH Alpha/Beta T CELL AND B CELL DEPLETION FOR PATIENTS WITH HEMATOLOGIC MALIGNANCIES

Estimation of the incidence and extent of acute and chronic GVHD. The overall incidence of acute GVHD, the incidence of Grade 4 acute GVHD and the incidence of chronic GVHD.

Children's Hospital of Philadelphia

Director, Blood and Marrow Transplant

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
Allogeneic Stem Cell Transplant With Alpha/Beta T AND B Cell Depletion for Hematologic Malignancies	NCT02323867	Leukemia Lymphoma Myelodysplasia	Alpha Beta T ce...	- 23 Years	Children's Hospital of Philadelphia
Allogeneic Stem Cell Transplant With Alpha/Beta T AND B Cell Depletion for Hematologic Malignancies	NCT02323867	Leukemia Lymphoma Myelodysplasia	Alpha Beta T ce...	- 23 Years	Children's Hospital of Philadelphia
Allogeneic Stem Cell Transplant With Alpha/Beta T AND B Cell Depletion for Hematologic Malignancies	NCT02323867	Leukemia Lymphoma Myelodysplasia	Alpha Beta T ce...	- 23 Years	Children's Hospital of Philadelphia

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