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Target dose of ≥ 5 x 10e6 CD34+ cells/kg of recipient body weight plus an additional 2 x10e9 mononuclear cells.

CIK cells

Mycophenolate Mofetil

Total Lymphoid Irradiation (TLI)

Everett Meyer, MD, PhD

Allogeneic stem cell transplantation (transplant of blood cells from another individual) is a treatment option for patients with myelodysplasia or myeloproliferative Disorders. During the course of this study, it will be evaluated whether a particular type of blood cell, called a cytokine-induced killer (CIK) cell, may add benefit to allogeneic stem cell transplantation. CIK cells are present in small quantities in the bloodstream but their numbers can be expanded after a brief period of nurturing in a laboratory.

Primary Objectives:

To determine the rate of conversion to FDC following infusion of allogeneic CIK cells among patients with MDS, therapy-related myeloid neoplasms, or MPD who receive non myeloablative preparative regimen of TLI / ATG followed by allogeneic HCT and consolidation with allogeneic CIK cells.

Secondary Objectives:

* To determine the 2 year overall survival (OS) and event free survival (EFS)
* To determine the incidence of acute GVHD following infusion of allogeneic CIK cells
* To assess the pre-transplant expression of NKG2D ligands in patients' bone marrow aspirates.

Post T-plant Infusion of Allogeneic Cytokine Induced Killer (CIK) Cells as Consolidative Therapy in Myelodysplastic Syndromes/Myeloproliferative Disorders

Post Transplant Infusion of Allogeneic Cytokine Induced Killer Cells as Consolidative Therapy After Non-Myeloablative Allogeneic Transplantation in Patients With Myelodysplasia or Myeloproliferative Disorders

Proportion of patients achieving full donor T-cell chimerism (FDC) by on or before Day 90 post non-myeloablative allogeneic transplant with allogeneic cytokine-induced killer (CIK) cells will be determined. FDC is defined as the attainment of \>95% donor type CD3+ cells. The outcome will be reported as number of participants who achieved full donor chimerism, a number without dispersion.

Overall survival (OS) is an expression of the number of participants that remain alive 2 years after cytokine-induced killer (CIK) infusion. The outcome will be reported as the number of participants alive 2 years after CIK infusion, a number without dispersion.

Event-free Survival (EFS) rate will be assessed on all enrolled participants and is defined as the duration of time after cytokine-induced killer (CIK) cell infusion that the participants remain alive with experiencing relapse, Grade 3 to 4 acute graft vs host disease (aGVHD), or death. The outcome will be reported as the number of participants, stratified by receipt of CIK cells, that did not experience a specified event, a number without dispersion.

Acute graft vs host disease (aGvHD) Grade 2 to 4 was staged \& graded using modified Keystone criteria, as below. The outcome is reported as the number of participants that experience Grade 2 to 4 aGvHD within 100 days and 1 year.

* Stage 1: Skin: rash \< 25% of skin. Liver: bilirubin 2 to 3 mg/dL. Gut: diarrhea 500 to 1000 mL/day or persistent nausea with positive biopsy for GvHD
* Stage 2: Skin: rash 25 to 50% of skin. Liver: bilirubin 3 to 6 mg/dL. Gut: diarrhea 1000 to 1500 mL/day.
* Stage 3: Skin: rash \> 50% of skin. Liver: bilirubin 6 to 15 mg/dL. Gut: diarrhea \> 1500 mL/day.
* Stage 4: Skin: generalized erythroderma with bulla formation. Liver: bilirubin \> 15 mg/dL. Gut: severe abdominal pain with or without ileus Grade of aGvHD was determined as follows.
* Grade 1: Stage 1-2 Skin + No Liver stage + No Gut stage
* Grade 2: Stage 3 Skin OR Stage 1 Liver or Stage 1 Gut
* Grade 3: No Skin stage + Stage 2 to 3 Liver Stage 2 to 4 Gut
* Grade 4: Stage 4 Skin + or Stage 2

Pre-transplant expression of natural-killer group 2, member D (NKG2D) ligands MIC A, MIC B, and the UL16 binding proteins (ULBPs) will be assessed in participants' bone marrow aspirates. The outcomes is expressed as the number of participants whose expression level for each ligand was elevated compared to background, represented by the known levels for individual without cancer.

Everett Meyer

Assistant Professor-Med

Target dose of ≥ 5 x 106 CD34+ cells/kg of recipient body weight plus an additional 2 x109 mononuclear cells.

CIK cells: Standard of care

Cyclosporine: 5 mg/kg, po

Mycophenolate Mofetil: 15 mg/kg, oral

Thymoglobulin: 7.5 mg/kg, IV

Allogeneic Cytokine Induced Killer Cells (CIK)

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Everett Meyer, Assistant Professor of Medicine (Blood and Marrow Transplantation)

Cytokine-induced killer (CIK) cells were infused in a subset of participants.

Full Donor Chimerism (FDC)

Cytokine-induced killer (CIK) cells were infused in a subset of participants. Participants that did not receive CIK cells were not included in this analysis.

Overall Survival (OS)

CIK-infused participants

Non-CIK-infused participants

All participants are reported. Cytokine-induced killer (CIK) cells were infused in a subset of participants.

Event-free Survival (EFS) Rate

All participants within 100 days

All participants within 1 year

CIK-infused participants within 100 days

CIK-infused participants within 1 year

Non-CIK-infused participants within 100 days

Non-CIK-infused participants within 1 year

Target dose of ≥ 5 x 10e6 CD34+ cells/kg of recipient body weight plus an additional 2 x10e9 mononuclear cells.

CIK cells: Standard of care

Cyclosporine: 5 mg/kg, po

Mycophenolate Mofetil: 15 mg/kg, oral

Thymoglobulin: 7.5 mg/kg, IV

Cytokine-induced killer (CIK) cells were infused in a subset of participants. Results are reported for both subsets and collectively, at 2 time points.

Number of Participants That Experience Grade 2 to 4 aGvHD Within 100 Days and 1 Year

Insufficient tumor sample materials from the pre-transplant diagnostic bone marrow aspirate was available for the research analysis. No analysis was conducted.

Pre-transplant Expression of Natural-killer Group 2, Member D (NKG2D) Ligands

CIK Cell Infusion

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Daniel Bernstein

We hope to determine the importance of different genes (including B receptors) in anthracycline-induced cardiomyopathy. This has important benefits to patients exposed to anthracyclines, as this could help determine whether certain individuals have increased susceptibility to cardiac injury.

There is a strong correlation between total doxorubicin dose and anti-tumor efficacy, however, the clinical utility of doxorubicin is severely limited by its cardiotoxicity. With improved methods of detecting subtle changes in cardiac function, e.g. alterations in left ventricular wall stress (1), the incidence of doxorubicin cardiotoxicity is now appreciated to be much higher than previously suspected, documented in 65% of long-term survivors of childhood cancer, even at doses as low as 228 mg/m2. This cardiotoxicity is dose-related, and higher doses are related to a higher incidence of clinical heart failure (2). Doxorubicin's cardiotoxicity is thought to be mediated through the generation of free radicals and through mitochondrial and membrane damage.

We wish to determine whether beta-receptor genotype affects anthracycline-induced cardiomyopathy. We will correlate beta-receptor genotype with difference in wall stress post-anthracycline exposure, and with difference in shortening fraction. We plan to recruit 300 patients over a two-year period. Inclusion criteria includes past exposure to anthracycline for cancer treatment and an echocardiogram 6 - 48 months after exposure to anthracyclines.

The mean difference in 1.) wall stress and 2.) shortening fraction between each minor allele subgroup and wild type subgroup, for both beta-1 and beta-2 will be assessed using unpaired t-test analyses . We will assess through multivariate linear regression whether there are interactions between differences in wall stress or fractional shortening and other variables such as age, gender, dose of anthracycline, type of anthracycline given, and time between anthracycline exposure and echocardiogram. Those who receive other cardiotoxic drugs (such as trastuzumab for breast cancer) will be analyzed separately.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Post T-plant Infusion of Allogeneic Cytokine Induced Killer (CIK) Cells as Consolidative Therapy in Myelodysplastic Syndromes/Myeloproliferative Disorders	NCT01392989	Neural Tube Def... Anemia Leukemia, Myelo... Bone Marrow Tra... Myelodysplastic... Myeloproliferat...	CIK cells Cyclosporine Mycophenolate M... Thymoglobulin Total Lymphoid ...	50 Years -	Stanford University
B-Receptor Signaling in Cardiomyopathy	NCT01135849	Carcinomas Amyloidosis Anal Cancer Anemia Cholangiocarcin... Transitional Ce... Bone Marrow Tra... Bone Cancer Cancer of Brain... Breast Cancer Carcinoma of th... Endocrine Cance... Esophageal Canc... Eye Cancer Gall Bladder Ca... Gastric (Stomac... Gastrooesophage... Gastrointestina... Gynecologic Can... Head and Neck C... Hepatobiliary N... Kidney (Renal C... Leukemia Lung Cancer Hodgkin Disease Lymphoma, Non-H... Mesothelioma Multiple Myelom... Myelodysplastic... Neuroendocrine ... Myeloproliferat... Pancreatic Canc... Prostate Cancer Skin Cancer Soft Tissue Sar... Testicular Canc... Thymus Cancer Thyroid Cancer		- 40 Years	Stanford University
Post T-plant Infusion of Allogeneic Cytokine Induced Killer (CIK) Cells as Consolidative Therapy in Myelodysplastic Syndromes/Myeloproliferative Disorders	NCT01392989	Neural Tube Def... Anemia Leukemia, Myelo... Bone Marrow Tra... Myelodysplastic... Myeloproliferat...	CIK cells Cyclosporine Mycophenolate M... Thymoglobulin Total Lymphoid ...	50 Years -	Stanford University
B-Receptor Signaling in Cardiomyopathy	NCT01135849	Carcinomas Amyloidosis Anal Cancer Anemia Cholangiocarcin... Transitional Ce... Bone Marrow Tra... Bone Cancer Cancer of Brain... Breast Cancer Carcinoma of th... Endocrine Cance... Esophageal Canc... Eye Cancer Gall Bladder Ca... Gastric (Stomac... Gastrooesophage... Gastrointestina... Gynecologic Can... Head and Neck C... Hepatobiliary N... Kidney (Renal C... Leukemia Lung Cancer Hodgkin Disease Lymphoma, Non-H... Mesothelioma Multiple Myelom... Myelodysplastic... Neuroendocrine ... Myeloproliferat... Pancreatic Canc... Prostate Cancer Skin Cancer Soft Tissue Sar... Testicular Canc... Thymus Cancer Thyroid Cancer		- 40 Years	Stanford University
Ph II of Non-myeloablative Allogeneic Transplantation Using TLI & ATG In Patients w/ Cutaneous T Cell Lymphoma	NCT00896493	Mycoses Sezary Syndrome Lymphoma, T-Cel... Bone Marrow Tra... Lymphoma, Non-H... Cutaneous T-cel...	anti-thymocyte ... cyclosporine Lymphoid radiat...	18 Years -	Stanford University

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