Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Rare Diseases

Leukemia

Lymphoma

Hematologic Neoplasms

Hematologic Diseases

Lymphosarcoma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Infective Agents

Amino Acids

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Melphalan

Lenograstim

Mycophenolic Acid

Thiotepa

Mechlorethamine

Mesna

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antitubercular Agents

Enzyme Inhibitors

Adjuvants, Immunologic

Phenylalanine

Participants undergo a preparative regimen of total lymphoid irradiation, fludarabine, cyclophosphamide, fludarabine, thiotepa, melphalan, and mycophenolate mofetil, followed by HPC,A infusion and TC-NK infusion. They also receive G-CSF and mesna.

Cells for infusion are prepared using the CliniMACS System.

Participants receive total lymphoid irradiation over four doses.

Total Lymphoid Irradiation

Participants received infusions of HPC,A (CD34+ selected) and HPC,A (CD45RA depleted).

HPC,A Infusion

TC-NK Infusion

Participants receive G-CSF subcutaneously or intravenously.

Donors receive G-CSF subcutaneously during cell mobilization.

G-CSF

Mesna is generally dosed at approximately 25% of the cyclophosphamide dose. It is generally given intravenously prior to and again at 3, 6 and 9 hours following each dose of cyclophosphamide.

The mechanism of action of the CliniMACS Cell Selection System is based on magnetic-activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can then be separated in a magnetic field using an immunomagnetic label specific for the cell type of interest, such as CD3+ human T cells.

CliniMACS

Mycophenolate mofetil

Brandon M. Triplett, 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) or matched unrelated donor (MUD) identified, will receive a haploidentical donor HCT with additional natural killer (NK) cells.

The investigators anticipate enrollment of 75 donors and 75 recipients.

PRIMARY OBJECTIVE:

* To estimate the rate of successful engraftment at day +42 post-transplant in patients who receive haploidentical donor stem cell plus NK cell transplantation with TLI based conditioning regimen for high risk hematologic malignancy.

SECONDARY OBJECTIVES:

* Estimate the incidence of malignant relapse, event-free survival, and overall survival 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.

Donors will undergo G-CSF mobilization of peripheral blood stem cells (PBSC) prior to undergoing two apheresis collections of hematopoietic progenitor cells (HPC,A) and one apheresis collection of therapeutic cell product of purified natural killer cells (TC-NK).

The HPC products will be T-cell depleted (TCD) using the investigational CliniMACS device. CD34+ enrichment and CD45RA depletion will be utilized on sequential HPC grafts.

Participants will undergo a preparative regimen of total lymphoid irradiation, fludarabine, cyclophosphamide, granulocyte colony stimulating factor (G-CSF), thiotepa, and melphalan. This is followed by infusions of donor cells that have been prepared using the CliniMACS system: HPC,A (CD34+ selected), HPC,A (CD45RA depleted), and TC-NK.

Haploidentical Donor Hematopoietic Progenitor Cell and NK Cell Transplantation for Hematologic Malignancy

Haploidentical Donor Hematopoietic Progenitor Cell and Natural Killer Cell Transplantation With a TLI Based Conditioning Regimen in Patients With Hematologic Malignancies

Neutrophil engraftment will be determined using the parameters put forth by the Center for International Blood and Marrow Registry. Assessments will be made upon review of daily complete blood count and serial chimerism studies. Successful engraftment for the purposes of this objective will be patients who do not experience graft failure.

Bone marrow studies for disease status evaluation will be performed at 1-year post-transplant. Testing will include a research evaluation for minimal residual disease.

The one-year event free survival is defined by the patient who has neither experienced relapse nor death within one year after post transplantation. And the rate is calculated by computing the ratio between total number of one year event free survival patients and the total number of patients.

The one-year survival is defined by the patient who has not died within one year after post transplantation. And the rate is calculated by computing the ratio between total number of one year survival patients and the total number of patients.

Acute and chronic graft-vs.-host disease will be evaluated using the standard grading criteria. The estimate will be the number of recipients who experienced GVHD divided by the total number of patients considered in this group.

Estimate the proportion of patients died within 100 days after the transplantation who has not experienced a relapse. The estimate will be the number of TRM divides the total number of patients considered in this group.

Ongoing assessment of toxicity will be done using the NCI CTCAE version 3.0. Acute and chronic graft-vs.-host disease will be evaluated using the standard grading criteria. The severity of acute GvHD and chronic GvHD will be described. The analysis for this objective will be performed when the last evaluable participant has been followed for 100 days post transplant. Acute GvHD is graded from 1-4 with 4 being the worst outcome.

Ongoing assessment of toxicity will be done using the NCI CTCAE version 3.0. Acute and chronic graft-vs.-host disease will be evaluated using the standard grading criteria. The severity of acute GvHD and chronic GvHD will be described. The analysis for this objective will be performed when the last evaluable participant has been followed for 1 year post-transplant. Chronic GvHD is graded as "mild", "moderate" or "severe" with "severe" being the worst outcome.

Assisi Foundation

St. Jude Children's Research Hospital

Recipient participants were followed for all NCI Grade III-V adverse events from the start of conditioning through the first-year post HCT, regardless of their relationship to the treatment given. Clinically significant NCI Grade I-II adverse events that are judged to be related/possibly related may be collected per the discretion and judgment of the PI. Adverse events that affected more than 5 participants are included in this description.

Participants meeting eligibility criteria and who completed study therapy: haploidentical stem cell transplantation with additional natural killer (NK) cells and total lymphoid irradiation (TLI) based conditioning regimen. Participants who received a therapeutic variance (maraviroc) are included.

Experimental: Transplant Recipients

Participants meeting eligibility criteria and who completed study therapy: haploidentical stem cell transplantation with additional natural killer (NK) cells and total lymphoid irradiation (TLI) based conditioning regimen. Participants who received a therapeutic variance (maraviroc) are excluded.

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Donor relationship to patient: Father, Mother, Sibling, Other.

Age was evaluated at the time of transplantation.

Number of Transplant Recipients With Successful Engraftment

Number of Transplant Recipients With Malignant Relapse

Event-free Survival

Overall Survival

Number of Transplant Recipients With Acute Graft Versus Host Disease (aGVHD)

Number of Transplant Recipients With Chronic Graft Versus Host Disease (cGVHD)

Number of Transplant Recipients With Acute and/or Chronic Graft Versus Host Disease (GVHD)

Number of Transplant Recipients With Transplant-related Mortality (TRM)

Ongoing assessment of toxicity will be done using the NCI CTCAE version 3.0. Acute and chronic graft-vs.-host disease will be evaluated using the standard grading criteria. The severity of acute GvHD and chronic GvHD will be described. The analysis for this objective will be performed when the last evaluable participant has been followed for 100 days post-transplant.

Severity of Acute Graft Versus Host Disease (aGVHD)

Severity of Chronic Graft Versus Host Disease (cGVHD)

Participants undergo a preparative regimen of total lymphoid irradiation, fludarabine, cyclophosphamide, fludarabine, thiotepa, melphalan, and mycophenolate mofetil, followed by HPC,A infusion and TC-NK infusion. They also receive G-CSF and mesna.

Cells for infusion are prepared using the CliniMACS System. Total Lymphoid Irradiation: Participants receive total lymphoid irradiation over four doses. Fludarabine: Given IV.

Cyclophosphamide: Given IV. Thiotepa: Given IV. Melphalan: Given IV. HPC,A Infusion: Participants received infusions of HPC,A (CD34+ selected) and HPC,A (CD45RA depleted). TC-NK Infusion: Participants receive infusions of TC-NK.

G-CSF: Participants receive G-CSF subcutaneously or intravenously. Donors receive G-CSF subcutaneously during cell mobilization.

Mesna: Mesna is generally dosed at approximately 25% of the cyclophosphamide dose. It is generally given intravenously prior to and again at 3, 6 and 9 hours following each dose of cyclophosphamide.

CliniMACS: The mechanism of action of the CliniMACS Cell Selection System is based on magnetic-activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can then be separated in a magnetic field using an immunomagnetic label specific for the cell type of interest, such as CD3+ human T cells.

Mycophenolate mofetil: Given intravenously or orally.

Spots Global Cancer Trial Database for Haploidentical Donor Hematopoietic Progenitor Cell and NK Cell Transplantation for Hematologic Malignancy

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