Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Analgesics

Etoposide

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Etoposide phosphate

Interleukin-2

Clofarabine

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antimetabolites

Enzyme Inhibitors

Analgesics, Non-Narcotic

Stratum 1 (AML in complete remission)

Cyclophosphamide 60 mg/kg IV Day -7 Fludarabine 25 mg/m2/day IV Days -6 through -2 Donor pheresis Day -1 Start IL-2 on Day -1, then 3 times per week x 2 weeks NK Cell purification and infusion on Day 0

Stratum 2 (AML that is refractory or relapsed or AML with increasing minimal residual disease)

Clofarabine 40 mg/m2 IV, days -6 through -2 Etoposide 100 mg/m2 IV, days -6 through -2 Cyclophosphamide 400 mg/m2 IV, days -6 through 02 Donor pheresis Day -1 Start IL-2 Day -1, and then 3 times per week x 2 weeks NK Cell purification and infusion on Day 0.

See Detailed Description section for additional details of treatment interventions.

Cyclophosphamide, Fludarabine, Clofarabine, Etoposide, Interleukin-2

Natural Killer Cell Infusion

CliniMACS System

Jeffrey E. Rubnitz, M.D.

The purpose of this study is to assess the safety and efficacy of infusing natural killer cells from a donor as treatment for patients with acute myeloid leukemia in remission or who have experienced relapse.

Natural killer (NK) cells extracted from a \[parental\] donor are infused intravenously. Most patients are given a multi-agent chemotherapeutic conditioning regimen prior to the infusion. The conditioning regimen may be omitted for patients who have previously received traditional stem cell transplant.

Details of Treatment Plan:

Stratum 1 (AML in complete remission)

Cyclophosphamide 60 mg/kg IV Day -7 Fludarabine 25 mg/m2/day IV Days -6 through -2 Donor pheresis Day -1 Start IL-2 on Day -1, then 3 times per week x 2 weeks NK Cell purification and infusion on Day 0

Stratum 2 (AML that is refractory or relapsed or AML with increasing minimal residual disease)

Clofarabine 40 mg/m2 IV, days -6 through -2 Etoposide 100 mg/m2 IV, days -6 through -2 Cyclophosphamide 400 mg/m2 IV, days -6 through 02 Donor pheresis Day -1 Start IL-2 Day -1, and then 3 times per week x 2 weeks NK Cell purification and infusion on Day 0.

For patients who have received prior SCT, the conditioning regimen may be omitted if the NK cells are obtained from the original SCT donor.

Cytokine regimen (stratum 1 and 2): 1 million units/m2 of IL-2 given subcutaneously three times per week for two weeks (6 doses) starting on the evening of day -1.

NK Cell Transplantation (stratum 1 and 2): NK cells from haplo-identical family donor will be infused on day 0.

Natural Killer (NK) Cell Transplantation for AML

Pilot Study Of Haplo-Identical Natural Killer Cell Transplantation For Acute Myeloid Leukemia

Document the number of patients experiencing grade 3 or 4 toxicities during conditioning and up to 100 days post-transplant. Toxicities were identified using Common Toxicity Criteria V 3.0 criteria.

Document the proportion of patients experiencing grade 3 or 4 toxicities during conditioning and up to 100 days post-transplant. Toxicities were identified using Common Toxicity Criteria V 3.0 criteria.

NK cell engraftment defined as NK cell chimerism in recipients.

The maximum percent of donor NK cell in recipients during a four-week period after NK cell infusion.

The percent of detectable donor NK cells in recipients at 28 days after NK cell infusion. Three of 10 participants had detectable donor cells at week 4. The results report the percent of detectable cells in the 3 participants.

The time elapsed after transplantation in days until peak KIR-mismatched donor NK cell expansion was reached in recipients

Number of KIR-mismatched donor NK cells in recipients' blood at day 2 and day 14 post NK cell infusion.

NK cells in recipient achieving ability to lyse target cell line (K562) within normal range established by donor NK cells.

For Arm 1, the efficacy of NK cell transplantation will be reported as the proportion of participants who achieve complete or partial remission. Kaplan-Meier estimates of relapse-free survival and confidence interval was determined by binomial distribution because no events were observed. The binomial interval is based on the number of patients at risk.

Overall survival is defined as the time relapse from on study date to death with those alive at last follow up date censored. The Kaplan-Meier method was used to compute survival probability estimates and confidence interval was determined by binomial distribution (for no events or all events) or by log hazard method. The binomial interval is based on the number of patients at risk.

The confidence intervals for Arm 1 and Arm 2a were determined by binomial distribution.

The confidence interval for Arm 2b was determined by log hazard method.

St. Jude Children's Research Hospital

AML in complete remission (stratum 1). AML in complete remission is defined as trilineage hematopoietic recovery with less than 5% blasts in the marrow. Participants received a traditional conditioning regimen of cyclophosphamide and fludarabine prior to NK cell transplantation.

Arm 1: Conditioning Regimen: Cyclophosphamide/Fludarabine

AML that is refractory or relapsed or AML with increasing minimal residual disease (MRD). Participants enrolled prior to Amendment 2.0 received a traditional conditioning regimen of cyclophosphamide and fludarabine prior to NK cell transplantation.

Refractory: ≥ 20% leukemic blasts in the bone marrow or no decrease in the percentage of blasts in the bone marrow (e.g., if a patient starts with 15% blasts and still has 15% blasts, he would have refractory disease).

Relapse: presence of ≥ 20% leukemic blasts in the bone marrow or the development of extramedullary disease after CR is achieved.

Increasing Minimal Residual Disease (MRD) indicates higher MRD levels.

Arm 2a: Conditioning Regimen: Cyclophosphamide/Fludarabine

AML that is refractory or relapsed or AML with increasing minimal residual disease (MRD) (stratum 2). Participants enrolled after protocol Amendment 2 received a novel conditioning regimen of clofarabine, etoposide and cyclophosphamide prior to NK cell transplantation.

Arm 2b: Conditioning: Clofarabine/Etoposide/Cyclophosphamide

AML in complete remission (stratum 1). AML in complete remission is defined as trilineage hematopoietic recovery with less than 5% blasts in the marrow. Arm 1 participants received a traditional conditioning regimen of cyclophosphamide and fludarabine prior to NK cell transplantation.

AML that is refractory or relapsed or AML with increasing minimal residual disease (MRD) (stratum 2). Participants enrolled prior to Amendment 2.0 received a traditional conditioning regimen of cyclophosphamide and fludarabine prior to NK cell transplantation.

AML that is refractory or relapsed or AML with increasing minimal residual disease (MRD) (stratum 2). Participants enrolled after protocol Amendment 2.0 received a novel conditioning regimen of clofarabine, etoposide and cyclophosphamide prior to NK cell transplantation.

Total

Age, Continuous

Sex: Female, Male

Jeffrey Rubnitz, MD

Grade 3 and 4 toxicities were assessed using Common Toxicity Criteria V.3.0 The assessment period was from the date on therapy through 100 days post-transplant.

Number of Patients Experiencing Grade 3 or 4 Toxicities During Conditioning and up to 100 Days Post-transplant

Proportion of Patients Experiencing Grade 3 or 4 Toxicities During Conditioning and up to 100 Days Post-transplant

Arm 2 participants were not analyzed for this outcome as many of these patients proceeded to allogeneic stem cell transplantation following NK cell transplantation.

Duration of Engraftment of Natural Killer (NK) Cells

Percent of Peak NK Cell Chimerism

Three of 10 participants continued to have detectable donor NK cells at week 4.

Percent of Detectable Donor NK Cells at Day 28

Nine of the 10 participants in Arm 1 received KIR-mismatched NK donor cells.

Day That Maximum NK Cell Engraftment Was Reached

Day 2

Day 14

Number of KIR-mismatched NK Cells

Lysed within normal range

Did not Lyse within normal range

All 10 participants received NK donor cells; 9 of the 10 participants received KIR-mismatched NK donor cells.

Number of Participants With Evidence of NK Cells Lysing a Target Cell Line (K562)

Relapse-free Survival

Overall Survival

Participants with AML in complete remission (stratum 1). AML in complete remission is defined as trilineage hematopoietic recovery with less than 5% blasts in the marrow. Arm 1 participants received a traditional conditioning regimen of cyclophosphamide and fludarabine prior to NK cell transplantation.

Overall Study

Symptoms and General Pathology

Immune System Diseases

Syndrome

Lymphoma

Leukemia, Lymphoid

Hematologic Neoplasms

Leukemia, Lymphocytic, Chronic, B-Cell

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Preleukemia

Myelodysplastic Syndromes

Lymphoma, Non-Hodgkin

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Bone Marrow Diseases

Precancerous Conditions

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Myeloproliferative Disorders

Chronic Graft Versus Host Disease

Lymphosarcoma

Chronic Lymphocytic Leukemia

Chronic Myeloid Leukemia

Chronic Myeloproliferative Disorders

Micronutrients

Anti-Infective Agents

Antibodies

Antibodies, Monoclonal

Iron

Immunoglobulins

Carbamide Peroxide

The CliniMACS cell selection system (Miltenyi Biotec) will be used to enrich hematopoietic stem cells from related, haploidentical, HLA-matched donors, who matched on the A,B,C and DRB1, DQ loci.

The CliniMACS System is a cell selection device consisting of the following components:

1. Computer-controlled instrument;
2. Sterile disposable tubing set (PVC tubing, filters and bags connected to two separation columns containing an iron/plastic matrix)
3. Anti-CD34 antibody reagent (murine monoclonal antibody chemically coupled to a magnetic particle)
4. Wash buffer

Ginna G Laport, MD

To assess the proportion of patients with donor neutrophil engraftment within 30 days of allogeneic transplant. To assess the incidence of acute GvHD during the first 100 days after transplantation.

To assess the proportion of patients with donor neutrophil engraftment within 30 days of allogeneic transplant; assess the incidence of acute GvHD during the first 100 days after transplantation; and assess platelet engraftment, graft failure, chronic GvHD, clinical safety, and devise performance.

Haploid Allogeneic Transplant Using the CliniMACS System

A Feasibility Study Evaluating Haploidentical Allogeneic Transplantation Using the CliniMACS System in Patients With Advanced Hematologic Malignancies

Number of subjects recovering neutrophils, assessed as 1st of 3 consecutive days on which ANC \> 0.5x10e9/L

Number of subjects with acute GvHD (grade II-IV) within 100 days post-transplant, per the Consensus Conference on Acute GvHD Grading (Przepiorka D, et al. Bone Marrow Transplantation. 1995. 15:825-828).

Number of subjects recovering platelets to \> 20x10e9/L, assessed on the 7th day unsupported by platelet transfusions

Ginna Laport

Associate Professor of Medicine

The CliniMACS cell selection system (Miltenyi Biotec) will be used to enrich hematopoietic stem cells from related, haploidentical, HLA-matched donors, who matched on the A,B,C and DRB1, DQ loci.

CliniMACS System: The CliniMACS System is a cell selection device consisting of the following components:

1. Computer-controlled instrument;
2. Sterile disposable tubing set (PVC tubing, filters and bags connected to two separation columns containing an iron/plastic matrix)
3. Anti-CD34 antibody reagent (murine monoclonal antibody chemically coupled to a magnetic particle)
4. Wash buffer

Haploidentical Allogeneic Transplant Using CliniMACS System

The CliniMACS cell selection system (Miltenyi Biotec) will be used to enrich hematopoietic stem cells from related, haploidentical, HLA-matched donors, who matched on the A,B,C and DRB1, DQ loci.

The CliniMACS System is a cell selection device consisting of the following components:

1. Computer-controlled instrument;
2. Sterile disposable tubing set (PVC tubing, filters and bags connected to two separation columns containing an iron/plastic matrix)
3. Anti-CD34 antibody reagent (murine monoclonal antibody chemically coupled to a magnetic particle)
4. Wash buffer

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Natural Killer (NK) Cell Transplantation for AML	NCT00187096	Acute Myeloid L...	Cyclophosphamid... Natural Killer ... CliniMACS Syste...	- 21 Years	St. Jude Children's Research Hospital
Natural Killer (NK) Cell Transplantation for AML	NCT00187096	Acute Myeloid L...	Cyclophosphamid... Natural Killer ... CliniMACS Syste...	- 21 Years	St. Jude Children's Research Hospital
Haploid Allogeneic Transplant Using the CliniMACS System	NCT00185679	Acute Myelogeno... Chronic Myeloge... Myelodysplastic... Non-Hodgkin's L... Chronic Lymphoc...	CliniMACS Syste...	18 Years - 50 Years	Stanford University

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