Blood and Lymph Conditions

All Conditions

Neoplasms

Lymphatic Diseases

Hematologic Neoplasms

Hematologic Diseases

Antipyretics

Analgesics

All Drugs and Chemicals

Anti-Allergic Agents

Antiemetics

Central Nervous System Depressants

Gastrointestinal Agents

Dermatologic Agents

Acetaminophen

Diphenhydramine

Promethazine

All patients will be registered in OnCore under this protocol as well as the specific treatment protocol.

* Pre-infusion treatment using intravenous hydration, acetaminophen and diphenhydramine hydrochloride
* Unlicensed Umbilical Cord Blood Infusion according to institutional guidelines.

  * Infusion of minimally manipulated unlicensed UCB units:
  * vital signs Monitoring during and after UCB infusion:
  * Management of infusion reactions
* Post-transplant care and follow-up: will be done according to the disease specific treatment protocol and institutional guidelines.

Infusion of Minimally Manipulated UCB Units - the UCB unit will be infused through a central line according to institutional guidelines.

Umbilical Cord Blood (UCB)

Claudio Brunstein, MD

John Wagner, MD

For the next 5-10 years or possibly longer, a high proportion of the Cord Blood Banks (CBB) inventory worldwide will be composed of unlicensed umbilical cord blood (UCB) units. While Food and Drug Administration (FDA)-licensed units will be prioritized, it will always be possible that an unlicensed unit will have known attributes, making it a better source of cells for the given indication. Because of the wide variety of current and potential indications as a source of cells for hematopoietic reconstitution or other form of cellular therapy, it is critical that the investigators have access to unlicensed UCB units.

Patients will receive intravenous hydration, acetaminophen and diphenhydramine hydrochloride (or appropriate alternative regimen) approximately 30 minutes prior to UCB infusion with doses adjusted for subject age and weight unless otherwise specified in the specific treatment protocol. Additional treatments will vary with the specific use of the UCB cells as specified in institutional review board (IRB)-approved disease-specific protocols at the University of Minnesota.

Infusion of Cell Populations From Unlicensed Umbilical Cord Blood Units

Documentation of events for the purpose of this study will only be for those events at least possibly related to the unlicensed UCB. Monitoring for acute infusional toxicities will end 24 hours after the umbilical cord blood (UCB) infusion.

point estimations and 95% confidence intervals of serious infusion reaction

Upon thawing (e.g., number of CD34 and colony forming cells for hematopoietic products or number of CD4+/CD25+/CD127- cells for Treg products prior to further manipulation).

Point estimations and 95% confidence intervals of incidences mislabeled UCB units

Determine if bacterial contamination, poor cell recoveries, shipment of mislabeled units, blood borne pathogen transmission or serious infusion reactions are more prevalent in units from specific CBBs.

Masonic Cancer Center, University of Minnesota

Symptoms and General Pathology

Immune System Diseases

Rare Diseases

Syndrome

Leukemia

Leukemia, Myeloid

Preleukemia

Myelodysplastic Syndromes

Lymphoma

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Hodgkin Disease

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Immunoproliferative Disorders

Bone Marrow Diseases

Myeloproliferative Disorders

Chronic Disease

Disease Attributes

Myeloid Leukemia

Chronic Graft Versus Host Disease

Lymphosarcoma

Chronic Myeloid Leukemia

Hodgkin Lymphoma

Chronic Myeloproliferative Disorders

Antineoplastic Agents

Antirheumatic Agents

Anti-Infective Agents

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Cyclosporine

Cyclosporins

Mycophenolic Acid

Thiotepa

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

There are three chemotherapy drugs involved. They are called fludarabine (5 doses), cyclophosphamide (1 dose), and thiotepa (2 doses). Also two days of radiation therapy. This is called Total Body Irradiation or TBI. The TBI if given for two days before, the transplant. On transplant day, the cord blood cells will be given through a catheter. The immune suppressing drugs given are called cyclosporine-A (CSA) and mycophenolate mofetil (MMF). These will be started 3 days before the transplant and will be given through the catheter. Later they can be given as tablets.

Cyclophosphamide 50 mg/kg/dose x 1 IV day -6 (1 dose) Fludarabine 30 mg/m2/dose x 5 IV days -6 to -2 (5 doses) Thiotepa 5 mg/kg/dose x 2 IV days -5 to -4 (2 doses) TBI 200 cGy/dose x 2 days -2 to -1 (2 doses). On transplant day, the cord blood cells will be given through your catheter. The immune suppressing drugs you will receive are called cyclosporine-A (CSA) and mycophenolate mofetil (MMF). These will be started 3 days before the transplant and will be given through your catheter. Later they can be given as tablets.

fludarabine, cyclophosphamide, thiotepa, radiation therapy, unrelated donor umbilical cord blood graft

Juliet Barker, MBBS

The traditional way of doing a donor transplant is to give high doses of chemotherapy and radiation before giving the stem cells. However, high doses of chemotherapy and radiation can have serious side-effects. The doctors think that the transplant will be safer and more likely to be successful with reduced doses of chemotherapy and radiation. The purpose of this study is to find out how good a combination of chemotherapy and radiation at reduced doses followed by a cord blood transplant are at treating cancer.

The stem cells chosen for the transplant are from umbilical cord blood. Umbilical cord blood is collected from healthy newborn babies and frozen. One cord blood collection is called a "cord blood unit." On transplant day, the cord blood will be given through the catheter just like a blood transfusion. Transplants done this way have been successful. However, this type of transplant is fairly new. Therefore, it is important to study it so the doctors can better understand how it works.

Most blood or bone marrow transplants using donor stem cells are done as part of a study. When patients are on a study we test new ways of treating them which we think may be better than the old ways. We collect information about the result of this treatment so we can understand how well the treatment works. This is so we can learn better ways to treat our patients.

Conditioning Regimen and the Transplantation of Unrelated Donor Umbilical Cord Blood in Patients With Hematologic Malignancies.

A Reduced Intensity Conditioning Regimen and the Transplantation of Unrelated Donor Umbilical Cord Blood in Patients With Hematologic Malignancies.

To obtain a preliminary estimate of progression free survival at 1 year post UCBT. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Successful primary donor engraftment = neutrophill recovery within the first 45 days after transplant and partial/complete donor chimerism (\>/= 10%)

The day 100 cumulative incidence of sustained CB-derived neutrophil engraftment.

The day 100 cumulative incidence of sustained CB-derived platelet engraftment to \>/= 20 x 10\^9/L

Memorial Sloan Kettering Cancer Center

Participants With Hematologic Malignancies

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Progression Free Survival/PFS at 1 Year Post UCBT.

Haplo-dCBT with early haplo-derived myeloid bridge

Haplo-dCBT with transient haplo-derived bridge with second neutrophil nadir

Haplo-dCBT with no bridge

Remaining dCBT recipient

43 haplo-dCBT recipients in this analysis 43 dCBT recipient

Number of Participants With Neutrophil Recovery Post Allograft for Haplo-dCBT Recipients

Percentage of Participants With Sustained CB-derived Neutrophil Engraftment

Percentage of Participants With Sustained CB-derived Platelet Engraftment

Overall Study

Heart and Blood Diseases

Leukemia, Myeloid, Acute

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Anemia

Multiple Myeloma

Neoplasms, Plasma Cell

Anemia, Aplastic

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoma, Non-Hodgkin

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Precancerous Conditions

Leukemia, B-Cell

Bone Marrow Failure Disorders

Pancytopenia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Aplastic Anemia

Chronic Lymphocytic Leukemia

Acute Graft Versus Host Disease

Tacrolimus

After a preparative regimen the patient will receive an infusion of one or two umbilical cord blood unit(s) (UBC). The UBC unit(s) will be thawed according to methods of Rubinstein et al. If two products are used, they will be administered sequentially on the same day 1-6 hours apart. Tacrolimus and mycophenolate mofetil (MMF) will be used for GVHD prophylaxis. On day +30, +60, +100, +180, and +365 the chimeric status of patients will be interpreted by variable number tandem repeat (VNTR) analysis. Immune reconstitution (Digeorge Panel) will also be checked at these time points.

Infusion will occur after preparative regimen in one or two UCB unit(s). If two products are used, they will be administered sequentially on the same day 1-6 hours apart. Tacrolimus and mycophenolate mofetil (MMF) will be used for GVHD prophylaxis.

umbilical cord blood (UCB)

Michael Craig, MD

Hematopoietic progenitor cell (HPC- primitive cells in the blood, bone marrow and umbilical cord that can restore the bone marrow) transplant can be a curative therapy for the treatment of hematologic malignancies (a disease of the bone marrow and lymph nodes). The source of cells used for the transplant comes from related (sibling) and in cases where there is no sibling match, from unrelated donors through the National Marrow Donor Program. The availability of a suitable donor can be a significant obstacle for patients who need a transplant but do not have a matched donor. Cord blood that has been harvested from an umbilical cord shortly after birth has a rich supply of cells needed for transplant. These stored cord bloods are now being used to transplant adults without a matched donor

Advantages to using cord blood includes a readily available source of cells with no risk to the donor during the collection process, immediate source of cells in urgent situations (no lengthy donor work-up)and a reduction in infectious disease transmission to the recipient.

One of the main disadvantages is the cord blood has a small number of cells needed for transplant. In an adult, usually two cords are needed and large recipients do not qualify because they need too many cells.

This study will use two different preparative regimens (chemotherapy and radiation) followed by one or two umbilical cord units (UBC). The preparative regimen used will be chosen by the physician and is based on patient's age, disease and medical condition at the time of transplant.

Multiple objectives for this study include disease-free and overall survival, treatment related mortality, rate of cells taking hold, and the incidence and severity of the transplant complication called graft versus host disease (GVHD).

Allogeneic hematopoietic cell transplantation (allo- HCT) is a curative therapy for the treatment of hematological and non-hematological malignancies and certain non-malignant conditions. Bone marrow or peripheral blood from a Human Leukocyte Antigen (HLA) matched sibling donor is the most commonly used source of allogeneic stem cells. However, HLA matched siblings are available for less than one third of the patients who require allo-Stem Cell Transplant (allo-SCT). In the absence of an HLA matched sibling, volunteer unrelated donors or partially mismatched related donors (PMRD), stored cord blood may be used as a source of allogeneic stem cells. Stored cord blood has been used as a source of allogeneic stem cells in infants and children, but had early skepticism in adults because of concerns about the engraftment potential of the relatively limited number of stem cells. The number of stem cells in a unit of cord blood is generally one log less than the number of stem cells on an average collection of bone marrow from an adult for transplantation.

After the success of the first allogeneic umbilical cord blood transplantation in 1988, programs for banking screened unrelated donor CBSC have been initiated both in the United States and Europe. Dr Pablo Rubenstein started the first such bank at the New York Blood Center (NYBC) in 1993. Since its inception, the NYBC has provided unrelated donor cord blood stem cells for over 1000 transplants. Analysis of outcomes for the initial 562 transplant recipients from the NYBC revealed a cumulative rate of engraftment of 81% by day 42 for PMNs. and 85% by day 180 for platelets. Currently, approximately more than 100,000 cord blood units are available in cord blood banks worldwide and more than 2000 patients have received cord blood transplants from these banks. NetCord, an international cooperative group of cord blood banks, has developed a detailed set of standards for cord blood banking to facilitate international exchanges and to guarantee the quality of these products.

Cord Blood Unit Selection:

UCB units will be required to be a 4 to 6 of 6 HLA-A, -B antigen and -DRB1 allele match with the patient. Typing at HLA-C and -DQ will be obtained but not required in the match strategy. A minimum total nucleated cell (TNC) dose of \>2.0 x 107/kg at the time of freezing will be utilized when possible. When using double units, each unit should contain a minimum pre-cryopreserved TNC dose of 1.5 x 107/kg.

UCB Transplant Procedure:

There will be a myeloablative and reduced-intensity preparative regimen that can be given prior to infusion of cord product. The myeloablative approach will be selected in younger patients (\<50yo) with a HCT-CI score \<3. The reduced-intensity regimen will be selected for all older patients (\>50) or younger patients with a hematopoietic cell transplantation-specific comorbidity index (HCT-CI) score \>3. The reduced-intensity regimen will also be chosen for any patients being transplanted for indolent/follicular lymphomas, CLL, myeloma, or Hodgkin lymphoma; irrelevant of age or HCT-CI score. On a case by case basis, patients may receive a preparative regimen outside of their designated category as noted above with the approval of the PI, if deemed in the patient's best interest.

Unrelated Umbilical Cord Blood (UBC)Transplantation

Unrelated Umbilical Cord Blood (UCB) Transplantation

Defined as neutrophil recovery associated with donor engraftment within the first 60 days of transplant

Number of Participants with Overall survival at day 180 transplant.

West Virginia University

Systematic assessment of adverse events was completed through that participants all being followed per routine schedule for transplant patients with regular examinations by their care provider with adverse event discovery per standard assessment.

After a preparative regimen the patient will receive an infusion of one or two umbilical cord blood unit(s) (UBC). The UBC unit(s) will be thawed according to methods of Rubinstein et al. If two products are used, they will be administered sequentially on the same day 1-6 hours apart. Tacrolimus and mycophenolate mofetil (MMF) will be used for GVHD prophylaxis. On day +30, +60, +100, +180, and +365 the chimeric status of patients will be interpreted by VNTR analysis. Immune reconstitution (Digeorge Panel) will also be checked at these time points.

umbilical cord blood (UCB): Infusion will occur after preparative regimen in one or two UCB unit(s). If two products are used, they will be administered sequentially on the same day 1-6 hours apart. Tacrolimus and mycophenolate mofetil (MMF) will be used for GVHD prophylaxis.

Transplant

After a preparative regimen the patient will receive an infusion of one or two umbilical cord blood unit(s) (UBC). The UBC unit(s) will be thawed according to methods of Rubinstein et al. If two products are used, they will be administered sequentially on the same day 1-6 hours apart. Tacrolimus and mycophenolate mofetil (MMF) will be used for GVHD prophylaxis. On day +30, +60, +100, +180, and +365 the chimeric status of patients will be interpreted by variable number tandem repeat (VNTR) analysis. Immune reconstitution (Digeorge Panel) will also be checked at these time points.

umbilical cord blood (UCB): Infusion will occur after preparative regimen in one or two UCB unit(s). If two products are used, they will be administered sequentially on the same day 1-6 hours apart. Tacrolimus and mycophenolate mofetil (MMF) will be used for GVHD prophylaxis.

Age, Categorical

Number of Participants With Engraftment

Overall Survival at Day 180 Post-transplant

After a preparative regimen the patient will receive an infusion of one or two umbilical cord blood unit(s) (UBC). The UBC unit(s) will be thawed according to methods of Rubinstein et al. If two products are used, they will be administered sequentially on the same day 1-6 hours apart. Tacrolimus and mycophenolate mofetil (MMF) will be used for graft versus host disease (GVHD) prophylaxis. On day +30, +60, +100, +180, and +365 the chimeric status of patients will be interpreted by VNTR analysis. Immune reconstitution (Digeorge Panel) will also be checked at these time points.

umbilical cord blood (UCB): Infusion will occur after preparative regimen in one or two UCB unit(s). If two products are used, they will be administered sequentially on the same day 1-6 hours apart. Tacrolimus and mycophenolate mofetil (MMF) will be used for GVHD prophylaxis.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Infusion of Cell Populations From Unlicensed Umbilical Cord Blood Units	NCT01451502	Lymphatic Disea... Hematopoietic M...	Umbilical Cord ...	-	Masonic Cancer Center, University of Minnesota
Conditioning Regimen and the Transplantation of Unrelated Donor Umbilical Cord Blood in Patients With Hematologic Malignancies.	NCT00739141	Leukemia Myelodysplastic... Non-Hodgkins Ly... Chronic Myeloge... Hodgkins Lympho...	fludarabine, cy...	18 Years - 70 Years	Memorial Sloan Kettering Cancer Center
Unrelated Umbilical Cord Blood (UBC)Transplantation	NCT01768845	Chronic Myeloge... Acute Myelogeno... Myelodysplastic... Multiple Myelom... Hodgkin Lymphom... Non-Hodgkin Lym... Chronic Lymphoc... Acute Lymphocyt... Severe Aplastic...	umbilical cord ...	16 Years - 70 Years	West Virginia University

Spots Global Cancer Trial Database for umbilical cord blood (ucb)