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

Antineoplastic Agents

Antirheumatic Agents

Anti-Infective Agents

Antibodies

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Cyclosporine

Cyclosporins

Immunoglobulins

Immunoglobulins, Intravenous

Mesna

Participant with high-risk hematologic malignancies undergoing Hematopoietic Cell Transplantation, who do not have a suitable Human Leukocyte Antigen -matched related/sibling donor, Matched Unrelated Donor or Killer immunoglobulin receptors ligand mismatched haploidentical donor identified, will receive a single UCB unit.

Intervention: Preparative Regimen

Patients requiring two UCB units will be eligible for UCBT01 on the observational arm.

Intervention: Preparative Regimen

Fludarabine (75 mg/m2), fractionated total body irradiation (TBI) (12.0 Gy), and cyclophosphamide (120mg/kg) with mesna. Fludarabine will be given once a day at 25 mg/m2 for three days on day -10 to day -8, TBI will be given twice a day at 150 cGy for four days on day -7 to day -4, and cyclophosphamide will be given once a day for at 60mg/kg for two days on day -3 and day -2.

Post-transplantation immunosuppression with cyclosporine and MMF will begin on day -3. Cord Blood infusion will occur on day 0 and G-CSF will start on day +1.

Preparative Regimen

Amr Qudeimat, MD

In this study, participants with high-risk hematologic malignancies undergoing hematopoietic cell transplantation (HCT), who do not have a suitable human leukocyte antigen (HLA)-matched related/sibling donor (MSD), matched unrelated donor (MURD) or killer-immunoglobulin receptors (KIR) ligand mismatched haploidentical donor identified, will receive an umbilical cord blood transplantation (UCBT) using a myeloablative preparative regimen.

The preparative regimen includes fludarabine (75 mg/m2), fractionated total body irradiation (TBI) (10.0 Gy), and cyclophosphamide (120mg/kg) with mesna. Fludarabine will be given once a day at 25 mg/m2 for three days on day -10 to day -8, TBI will be given twice a day at 150 cGy for four days on day -7 to day -4, and cyclophosphamide will be given once a day for at 60mg/kg for two days on day -3 and day -2. Post-transplantation immunosuppression with cyclosporine and MMF will begin on day -3. Cord Blood infusion will occur on day 0 and G-CSF will start on day +1.

The primary objectives is to estimate the event-free survival (EFS) at one-year post-transplant for research participants with high-risk hematologic malignancies undergoing hematopoietic cell transplantation (HCT) using single unit umbilical cord blood (UCB).

Secondary objectives are:

* Describe the clinical outcome of patients undergoing a double unit UCBT.
* Estimate the incidence and severity of acute and chronic graft versus host disease (GVHD) of patients enrolled in the research arm.
* Estimate the incidence and time to neutrophil and platelet engraftment among patients enrolled in the research arm.
* Estimate the incidence of transplant related mortality (TRM) and transplant related morbidity in the first 100 days after transplantation among patients enrolled in the research

Exploratory Objectives are:

* Assess the relationship between pre-transplant minimal residual disease (MRD) with transplant outcomes.
* Record immune reconstitution parameters, including chimerism analysis, quantitative lymphocyte subsets, T cell receptor excision circle (TREC) and spectratyping. Immunophenotyping and functional assays of T, B and NK cells and lymphocytes will also be evaluated.
* Evaluate the determinants of engraftment.

Umbilical Cord Blood Transplantation In Patients With Hematologic Malignancies Using A Myeloablative Preparative Regimen

Estimate EFS for research participants at one-year post transplant by using single unit umbilical cord blood. The event is defined as relapse, graft failure, death due to any cause. The number of participants who did not experience any of those events (relapse, graft failure, death due to any cause) at year 1 post-transplant was given.

For patients enrolled in the observational arm (undergoing a double unit UCBT), the number of patients engrafted was given.

The number of observational arm patients who relapsed was given.

The number of observational arm patients who died was given.

The number of patients with TRM within the first 100 days post transplant was given.

The number of participants with incidence of acute GVHD by grade was given. Participants are graded on a scale from 1 to 4, with 1 being mild and 4 being severe.

Due to the small sample size, cumulative incidence analysis was not done. The incidence of chronic GVHD was evaluated using NIH Consensus Global Severity Scoring. The number of patients with incidence of chronic GVHD by severity was provided.

Platelet engraftment was defined as platelet count ≥20,000/mm\^3 for 3 consecutive tests performed on different days with no platelet transfusions in the preceding 7 days. Neutrophil engraftment will be defined as achieving ANC ≥ 500/mm3 for 3 consecutive tests performed on different days with evidence of donor cell engraftment. Descriptive statistics are provided.

TRM is death occurring in patients in continuous complete remission. The numbers of patients with TRM was given.

Any patient who had adverse events listed either as probable or definite in the first 100 days post-transplant are counted as transplant related morbidity. The number of patients with transplant-related morbidity was given.

The Hartwell Foundation

Assisi Foundation

St. Jude Children's Research Hospital

Participant with high-risk hematologic malignancies undergoing Hematopoietic Cell Transplantation, who do not have a suitable Human Leukocyte Antigen -matched related/sibling donor, Matched Unrelated Donor or Killer immunoglobulin receptors ligand mismatched haploidentical donor identified, will receive a single UCB unit.

Intervention: Preparative Regimen

Preparative Regimen: Fludarabine (75 mg/m2), fractionated total body irradiation (TBI) (12.0 Gy), and cyclophosphamide (120mg/kg) with mesna. Fludarabine will be given once a day at 25 mg/m2 for three days on day -10 to day -8, TBI will be given twice a day at 150 cGy for four days on day -7 to day -4, and cyclophosphamide will be given once a day for at 60mg/kg for two days on day -3 and day -2.

Post-transplantation immunosuppression with cyclosporine and MMF will begin on day -3. Cord Blood infusion will occur on day 0 and G-CSF will start on day +1.

Research Arm

Patients requiring two UCB units will be eligible for UCBT01 on the observational arm.

Intervention: Preparative Regimen

Preparative Regimen: Fludarabine (75 mg/m2), fractionated total body irradiation (TBI) (12.0 Gy), and cyclophosphamide (120mg/kg) with mesna. Fludarabine will be given once a day at 25 mg/m2 for three days on day -10 to day -8, TBI will be given twice a day at 150 cGy for four days on day -7 to day -4, and cyclophosphamide will be given once a day for at 60mg/kg for two days on day -3 and day -2.

Post-transplantation immunosuppression with cyclosporine and MMF will begin on day -3. Cord Blood infusion will occur on day 0 and G-CSF will start on day +1.

Observation Arm

Observational Arm

Total

Age, Continuous

Sex: Female, Male

Race/Ethnicity, Customized

Event Free Survival (EFS) for Research Participants

Number of Observational Arm Participants Engrafted

Number of Observational Arm Patients Who Relapsed

Number of Deaths of Observational Arm Patients

Patients requiring two UCB units will be eligible for UCBT01 on the observationalal arm.

Intervention: Preparative Regimen

Preparative Regimen: Fludarabine (75 mg/m2), fractionated total body irradiation (TBI) (12.0 Gy), and cyclophosphamide (120mg/kg) with mesna. Fludarabine will be given once a day at 25 mg/m2 for three days on day -10 to day -8, TBI will be given twice a day at 150 cGy for four days on day -7 to day -4, and cyclophosphamide will be given once a day for at 60mg/kg for two days on day -3 and day -2.

Post-transplantation immunosuppression with cyclosporine and MMF will begin on day -3. Cord Blood infusion will occur on day 0 and G-CSF will start on day +1.

Number of Observational Arm Patients With Transplant-related Mortality (TRM)

Patients requiring two UCB units will be eligible for UCBT01 on the observational arm.

Intervention: Preparative Regimen Preparative Regimen: Fludarabine (75 mg/m2), fractionated total body irradiation (TBI) (12.0 Gy), and cyclophosphamide (120mg/kg) with mesna. Fludarabine will be given once a day at 25 mg/m2 for three days on day -10 to day -8, TBI will be given twice a day at 150 cGy for four days on day -7 to day -4, and cyclophosphamide will be given once a day for at 60mg/kg for two days on day -3 and day -2.

Post-transplantation immunosuppression with cyclosporine and MMF will begin on day -3. Cord Blood infusion will occur on day 0 and G-CSF will start on day +1.

Number of Participants With Acute GVHD

Number of Participants With Chronic GVHD

Days to Platelets ≥20,000

Days to ANC ≥500

Those patients who did not reach engraftment are not included in the results provided below.

Time to Engraftment of Research Arm Participants

Incidence of Transplant-related Mortality (TRM)

The Number of Participants With Transplant-related Morbidity

Overall Study

Mohamed Sorror, MD

Comorbidity assessment in the field of HCT might be a burden on the medical team at the clinic or the research staff. This research study aims to explore and validate new methods, Claims-based and patient questionnaire-based, as alternatives to the standard chart-based method in order to facilitate comorbidity coding. The study aims to save time and effort of medical personnel and to ensure the inclusion of comorbidity information in all clinical trials and outcome research studies in order to improve the accuracy of treatment decision-making, patient assignment to appropriate HCT strategy and hence HCT outcomes.

Studies have shown the importance of pre-transplant comorbidities in predicting mortality after allogeneic HCT.

However, comorbidity assessment might be a burden on the medical team at the clinic or the research staff. This research study aims to explore and validate new methods as alternatives to the standard chart-based method in order to facilitate comorbidity coding. The study aims to save time and effort of medical personnel and to ensure the inclusion of comorbidity information in all clinical trials and outcome research studies in order to improve the accuracy of treatment decision-making, patient assignment to appropriate HCT strategy and hence HCT outcomes.

This study will investigate two parallel approaches aimed at simplifying comorbidity assessment and thereby facilitating wide-spread use of the HCT-CI. Patient questionnaire-based and Claims-based methods will be tested as possible alternative to the Chart-based method. primary outcome is prediction of non-relapse mortality. It is expected that once this method of comorbidity coding is validated, it will benefit physicians in non-academic institutions and community clinics.

Comparing Different Methods for Collection of Comorbidity Data Per the HCT-CI

Comparing Different Methods for Collection of Comorbidity Data Per the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI)

3 measures: the questionnaire-based and the claims-based methods versus the chart-based method.

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
Umbilical Cord Blood Transplantation In Patients With Hematologic Malignancies Using A Myeloablative Preparative Regimen	NCT01328496	Hematologic Mal... Disorder Relate... Hematopoietic M...	Preparative Reg...	- 21 Years	St. Jude Children's Research Hospital
Umbilical Cord Blood Transplantation In Patients With Hematologic Malignancies Using A Myeloablative Preparative Regimen	NCT01328496	Hematologic Mal... Disorder Relate... Hematopoietic M...	Preparative Reg...	- 21 Years	St. Jude Children's Research Hospital
Comparing Different Methods for Collection of Comorbidity Data Per the HCT-CI	NCT03434561	Hematopoietic M...		20 Years -	Fred Hutchinson Cancer Center

Spots Global Cancer Trial Database for hematopoietic malignancy