Neoplasms

Blood and Lymph Conditions

All Conditions

Hematologic Neoplasms

Hematologic Diseases

All Drugs and Chemicals

Antineoplastic Agents

Antirheumatic Agents

Anti-Infective Agents

Dermatologic 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

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Lymphoma

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoma, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

B-cell Lymphoma

Molgramostim

Sargramostim

Rituximab

Immunomodulating Agents

Antineoplastic Agents, Immunological

Immunologic Factors

Immunotherapy in Non-myeloablative Allogeneic Stem Cell Transplantation

GM-CSF = Granulocyte-Macrophage Colony-Stimulating Factor

250 micrograms subcutaneously 3 times a week for 4 weeks starting a day before the administration of Rituximab.

GM-CSF

375 mg/m\^2 by vein followed by 1000 mg/m\^2 weekly for 3 weeks for a total of 4 doses.

NK cells will be infused one week after the fourth dose of Rituximab and GM-CSF.

NK Cell Infusion

Issa F. Khouri, MD

The goal of this clinical research study is to find out if giving a boost of natural killer (NK) cells from a donor combined with Rituxan (rituximab), can help to control disease in patients who have already received an allogeneic stem cell transplant. The safety of this treatment will also be studied. Participants have recurrent chronic lymphocytic leukemia (CLL) or lymphoma after non-myeloablative stem cell transplantation.

Primary Objectives:

1.0 To determine the safety of Natural Killer (NK) cells and Rituximab + rhu-Granulocyte-macrophage colony-stimulating factor (GMCSF) in patients with persistent or recurrent B-cell lymphoid malignancies after non-myeloablative stem cell transplantation.

2.0 To determine factors associated with response.

Rituximab is designed to attach to lymphoma cells, causing them to die. GM-CSF and NK cells may increase rituximab's ability to kill these cells.

Before you can start treatment on this study, you will have what are called "screening tests." These tests will help the doctor decide if you are eligible to take part in this study. You will have your complete medical history recorded and a physical exam. Your blood (about 2 tablespoons) will be collected for routine tests. A bone marrow aspirate will be performed. To collect a bone marrow aspirate, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle. You will have computerized tomography (CT) scans as well as positron emission tomography (PET) or gallium scans to learn the status of your disease. Women who are able to have children must have a negative blood or urine pregnancy test.

If you are found eligible to take part in this study, you will receive treatment as an outpatient. You will receive GM-CSF 3 times a week for 4 weeks through a vein, starting the day before you receive the administration of rituximab. You will receive rituximab over 4 to 8 hours through a vein, once weekly for 4 weeks. You will also get a boost of NK cells from the same donor from whom you received your original transplant. These cells will be infused through a vein (over 30 to 60 minutes) after the 4th dose of rituximab. If you are receiving a cell infusion from somebody who you are not related to, the infusion may have to be done later if cells were not available as scheduled.

The CliniMACS System is a medical device that is used to separate types of blood cells from blood that is removed from the body during leukapheresis. These separated cells are processed for use in treatments such as stem cell transplants.

During this treatment, you will be examined as needed, and blood samples (1 tablespoon once or twice a week) will be taken for routine tests. You may need to receive blood transfusions during this study if your blood cell counts remain low.

You may be taken off this study if your disease gets worse or intolerable side effects occur.

You will have long-term, follow-up visits while on study. You will be seen at 4 to 6 weeks after you receive NK cell infusion; every 3 months during the first year; and then once a year. During each of these visits, you will have CT and PET scans, a bone marrow biopsy, and blood drawn (about 4 teaspoons) to learn the status of your disease.

This is an investigational study. Rituximab and GM-CSF are FDA approved and commercially available. NK cells are authorized by the FDA for use in research only. Up to 40 participants will take part in this study. All will be enrolled at the University of Texas (UT) MD Anderson Cancer Center.

Immunotherapy With NK Cell, Rituximab and Rhu-GMCSF in Non-Myeloablative Allogeneic Stem Cell Transplantation

Maximum tolerated dose (MTD) is the highest dose with 10 patients treated and 5 or fewer patients with DLT.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
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
Immunotherapy With NK Cell, Rituximab and Rhu-GMCSF in Non-Myeloablative Allogeneic Stem Cell Transplantation	NCT00383994	Lymphoma Leukemia Transplantation... Lymphoid Malign... Disorder Relate...	GM-CSF Rituximab NK Cell Infusio...	-	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for disorder related to transplantation