Blood and Lymph Conditions

All Conditions

Neoplasms

Rare Diseases

Anemia

Hematologic Neoplasms

Anemia, Aplastic

Hematologic Diseases

Bone Marrow Failure Disorders

Pancytopenia

Bone Marrow Diseases

Aplastic Anemia

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Rituximab

Antilymphocyte Serum

Thymoglobulin

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Transplant conditioning will consist of: ATG (2 mg/kg/day IV on days-8 through-6), fludarabine (30 mg/m\^2/d on days -5 through -2), TBI 400 cGy in 2 divided doses (days -2 and -1) and high dose cyclophosphamide given post stem cell infusion (50 mg/kg on days +3 and +4). One dose of Rituxan (200 mg/m\^2) will be given to reduce the risk of EBV viremia. The donor stem cell product will be derived from the peripheral blood with a target cell infusion of ≥8X10\^6 CD34 cells per recipient kg. Patients will receive post-transplant G-CSF starting on day +7. Patients will undergo donor/recipient bone marrow and peripheral chimerism studies at 30 and 100, and 6, 12, 18 and 24 months post allo HCT and thereafter, at the discretion of the treating clinician. Immune function and disease restaging will be performed at day 100 and 6, 12, 18, and 24 months and as otherwise clinically indicated by the treating physician.

Antithymocyte globulin (Rabbit)

fludarabine (30 mg/m2/d on days -5 through -2)

fludarabine

TBI 200 cGy (days -2 and -1) given post stem cell infusion

total body irradiation

cyclophosphamide given post stem cell infusion (50 mg/kg on days +3 and +4)

cyclophosphamide

Rituxan (200 mg/m2) will be given to reduce the risk of EBV viremia

Rituxan

Allogeneic Hematopoietic Stem Cell Transplantation

Roni Tamari, MD

The main purpose of this study is to learn if a new combination of chemotherapy, in combination with low-dose radiation, will be safe for the patient, and at the same time provide the best opportunity to cure the bone marrow cancer. The combination of chemotherapy and radiation described in the study is considered 'low intensity.' Although the chemotherapy agents used in this study and for transplant are FDA approved, the chemotherapy treatment and conditioning regimens or combinations listed in this consent are not yet FDA approved.

The CliniMACS device is FDA approved for one type of T cell depletion (positive selection of the stem cells) but not approved yet for other type of T cell depletion, which is being studied on this protocol. This pilot study, along with other studies will serve as the basis for FDA approval, if outcomes are favorable.

This is a pilot study to assess engraftment of a T cell depleted (TCD) graft following a reduced intensity conditioning regimen (RIC). The conditioning regimen will include total body irradiation (TBI), Fludarabine, anti-thymocyte globulin (ATG) and post transplant cyclophosphamide (PT-Cy). The graft will be TCD and will be composed of a TCR-α/β+ lymphocyte depletion stem cells and CD34+ selected stem cells.

T Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation Conditioned With a Reduced Intensity Regimen in Patients With Hematologic Malignancies and Aplastic Anemia

Allogeneic Hematopoietic Stem Cell Transplantation of α/β T-Lymphocyte Depleted Graft Conditioned With a Reduced Intensity Regimen in Patients With Hematologic Malignancies and Aplastic Anemia

Neutrophil engraftment (recovery of ANC) defined by an ANC ≥ 500/mm\^3 for 3 consecutive days

Memorial Sloan Kettering Cancer Center

Symptoms and General Pathology

Immune System Diseases

Syndrome

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Leukemia, Myelomonocytic, Juvenile

Myelodysplastic Syndromes

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Sarcoma

Lymphoma

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Sarcoma, Myeloid

Neoplasms by Histologic Type

Neoplasms, Connective and Soft Tissue

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Myeloproliferative Disorders

Myelodysplastic-Myeloproliferative Diseases

Chronic Disease

Disease Attributes

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Graft Versus Host Disease

Soft Tissue Sarcoma

Lymphosarcoma

Chronic Myeloid Leukemia

Acute Graft Versus Host Disease

Chronic Myeloproliferative Disorders

Myelodysplastic/myeloproliferative Disease

Anti-Infective Agents

Tacrolimus

Cytarabine

Plerixafor

Mycophenolic Acid

Busulfan

Vidarabine

Clofarabine

Antimetabolites

Antiviral Agents

Calcineurin Inhibitors

Enzyme Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antitubercular Agents

Anti-HIV Agents

Anti-Retroviral Agents

All study participants.

Interventions: clofarabine, cytarabine, busulfan, plerixafor, cyclophosphamide, antithymocyte globulin (rabbit), stem cells, tacrolimus, mycophenolate mofetil

Given on Day -9 and Day -8 (Day 0 is first stem cell infusion). Drug class: antineoplastic agent

clofarabine

cytarabine

Given on Day -7 and Day -6 (Day 0 is first stem cell infusion). Drug class: antineoplastic agent

busulfan

Given on Day -7 and Day -6 (Day 0 is first stem cell infusion). Drug class: Hematopoietic Stem Cell Mobilizer

Given on Day -5 and Day +4 (Day 0 is first stem cell infusion). Drug class: antineoplastic agent; immunosuppressive agent.

Given on Day -4, Day -3, Day -2, and Day -1 (Day 0 is first stem cell infusion). Drug class: immunosuppressive agent.

antithymocyte globulin (rabbit)

Patients undergo T cell replete Hematopoietic stem cell infusion on Day 0 and Day +1. Patients undergo natural killer (NK) cell transplantation on day +6 (Day 0 is first stem cell infusion).

stem cells

Given on Day +11 (Day 0 is first stem cell infusion). Drug class: immunosuppressive agent.

mycophenolate mofetil

Brandon M. Triplett, MD

The primary aim of this protocol is to evaluate if the one-year survival is significantly improved in the group of patients who receive a T-cell replete haploidentical donor hematopoietic cell transplant (HCT) with a novel reduced intensity conditioning regimen. Study population will consist of patients (21 years or under) with hematologic malignancies that have relapsed or are refractory after prior allogeneic transplant. Toxicity will be evaluated by the rate of transplant related mortality and the rates of moderate and severe graft-versus-host disease (GvHD) at day 100. The investigators will describe event-free, and disease-free survival at one year, as well as the rates of hematopoietic recovery and donor engraftment and study comprehensively immune reconstitution following T-cell replete haploidentical transplantation.

Patients with refractory hematologic malignancies, including those who develop recurrent disease after allogeneic hematopoietic cell transplantation, have a dismal prognosis. Historically, both regimen-related mortality and disease recurrence have been significant causes of treatment failure in this heavily pre-treated patient population. Our institution has utilized mismatched family member (haploidentical) donors for these patients for a number of years for the following reasons: (1) Only 30% of patients have matched related donors available; (2) transplantation can be performed more rapidly since the time to unrelated donor transplantation averages 3 to 4 months; (3) no other curative treatment options are available. These therapeutic interventions have been largely successful given the dismal prognosis in this patient group; however disease recurrence remains the most significant cause of treatment failure. To provide maximum benefit for this challenging population, the goals of a therapeutic transplant protocol should include: (1) a conditioning regimen that is well tolerated, even in a heavily pre-treated population; but it should also provide substantial antileukemia effects, and (2) should establish rapid immune recovery such that the patient may benefit from graft versus leukemia effect and early protection from life threatening infections while also limiting dangerous and counter-productive graft versus host disease.

The primary aim of this protocol will be to evaluate if the one-year survival is significantly improved in the group of patients receiving T-cell replete haploidentical donor HCT with a novel clofarabine, cytarabine, busulfan, plerixafor, cyclophosphamide, and ATG based reduced intensity conditioning regimen whose hematologic malignancy has relapsed or is refractory after prior allogeneic transplant. Toxicity will be evaluated by the rate of transplant related mortality and the rates of moderate and severe graft versus host disease at day 100. The investigators will also describe event-free, and disease-free survival at one year, as well as the rates of hematopoietic recovery and donor engraftment. Additionally, the investigators will study comprehensively immune reconstitution following T-cell replete haploidentical transplantation.

PRIMARY OBJECTIVE:

* Evaluate if the one-year survival is significantly improved in a group of children receiving a therapeutic regimen for high-risk hematologic malignancy that is relapsed or refractory despite previous allogeneic hematopoietic cell transplantation (HCT) using a novel reduced intensity conditioning and T-cell replete haploidentical donor hematopoietic stem cell plus NK cell transplantation.

SECONDARY OBJECTIVES:

* Estimate the incidence of malignant relapse, event-free survival, and disease free survival (DFS) at one-year post-transplantation.
* Estimate incidence and severity of acute and chronic (GVHD).
* Estimate the rate of transplant related mortality (TRM) in the first 100 days after transplantation.

T-Cell Replete Haploidentical Donor Hematopoietic Stem Cell Plus Natural Killer (NK) Cell Transplantation in Patients With Hematologic Malignancies Relapsed or Refractory Despite Previous Allogeneic Transplant

Evaluate the number of participants alive at 1 year. The number of participants surviving to one-year post-transplantation is given.

Estimate the incidence of malignant relapse at one year post-transplant. The number of participants with malignant relapse or progressive disease is given. Relapse was evaluated using standard WHO criteria for each disease.

Estimate the EFS at one-year post-transplantation. The event is defined as relapse or death due to any cause. The number of participants who were alive without relapse at one year post-transplant is reported.

Estimate the DFS at one-year post-transplantation. The event is defined as relapse or death due to relapse. The number of participants who did not relapse up to one year post transplant is reported.

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

The severity of chronic GVHD will be described. Chronic GVHD was evaluated using NIH Consensus Global Severity Scoring. The number of participants with chronic GVHD is given, organized by severity.

The number of participants who died due to TRM in the first 100 days post-transplant is given.

Assisi Foundation

St. Jude Children's Research Hospital

Study participants (excluding donors) who were enrolled to receive treatment with clofarabine, cytarabine, busulfan, plerixafor, cyclophosphamide, antithymocyte globulin (rabbit), stem cells, tacrolimus, and mycophenolate mofetil. Donors did not receive treatment and are not followed for data collection to answer the study objectives. They are therefore not included in the results reported here.

Treatment

Study participants (excluding donors) who were enrolled and underwent transplant. Donors did not receive treatment and are not followed for data collection to answer the study objectives. They are therefore not included in the results reported here.

Age, Continuous

Gender

Study participants (excluding donors) who were enrolled and underwent transplant.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
T Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation Conditioned With a Reduced Intensity Regimen in Patients With Hematologic Malignancies and Aplastic Anemia	NCT03531736	Myeloid Disease...	Antithymocyte g... fludarabine total body irra... cyclophosphamid... Rituxan Allogeneic Hema...	18 Years -	Memorial Sloan Kettering Cancer Center
T-Cell Replete Haploidentical Donor Hematopoietic Stem Cell Plus Natural Killer (NK) Cell Transplantation in Patients With Hematologic Malignancies Relapsed or Refractory Despite Previous Allogeneic Transplant	NCT01621477	Acute Lymphobla... Acute Myelocyti... Chronic Myelocy... Juvenile Myelom... Myelodysplastic... Hodgkin or Non-... Sarcoma, Myeloi...	clofarabine cytarabine busulfan Plerixafor cyclophosphamid... antithymocyte g... stem cells Tacrolimus mycophenolate m...	- 21 Years	St. Jude Children's Research Hospital
T Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation Conditioned With a Reduced Intensity Regimen in Patients With Hematologic Malignancies and Aplastic Anemia	NCT03531736	Myeloid Disease...	Antithymocyte g... fludarabine total body irra... cyclophosphamid... Rituxan Allogeneic Hema...	18 Years -	Memorial Sloan Kettering Cancer Center

Spots Global Cancer Trial Database for antithymocyte globulin (rabbit)