Heart and Blood Diseases

All Conditions

Heart Failure

Cardiomyopathies

Heart Diseases

Patients receive hMSCs IV over 10-20 minutes on days 1, 14, 21, and 28 and standard of care treatment for heart failure in the absence of disease progression or unacceptable toxicity.

Patients receive hMSCs transendocardially for a total of 15 injections and standard of care treatment for heart failure in the absence of disease progression or unacceptable toxicity.

Patients receive standard of care treatment for heart failure.

Best Practice

Laboratory Biomarker Analysis

Mesenchymal Stem Cell Transplantation

Amanda Olson, MD

This randomized pilot phase I trial studies the side effects of donor bone marrow derived mesenchymal stem cells in controlling heart failure in patients with cardiomyopathy caused by anthracyclines. Donor bone marrow derived mesenchymal stem cells may help to control symptoms of heart failure and improve heart function.

PRIMARY OBJECTIVE:

I. To demonstrate the safety of allogeneic human mesenchymal stem cells (hMSCs) administered by intravenous infusion and transendocardial injection in patients with left ventricular (LV) dysfunction and heart failure secondary to chemotherapy with anthracyclines.

SECONDARY OBJECTIVE:

I. To demonstrate the efficacy of allogeneic hMSCs administered by intravenous infusion and transendocardial injection in patients with left ventricular dysfunction (left ventricular ejection fraction \[LVEF\] \< 40%) and heart failure secondary to treatment with anthracyclines.

OUTLINE: Patients are randomized to 1 of 3 arms.

ARM I: Patients receive hMSCs intravenously (IV) over 10-20 minutes on days 1, 14, 21, and 28 and standard of care treatment for heart failure in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive hMSCs transendocardially for a total of 15 injections and standard of care treatment for heart failure in the absence of disease progression or unacceptable toxicity.

ARM III: Patients receive standard of care treatment for heart failure.

After completion of study treatment, patients are followed up periodically.

Donor Bone Marrow Derived Mesenchymal Stem Cells in Controlling Heart Failure in Patients With Cardiomyopathy Caused by Anthracyclines

Randomized 3-Arm Trial With Standard of Care Alone vs Either Intravenous Infusion or Transendocardial Injection of Allogeneic Bone Marrow Derived Multipotent Mesenchymal Stromal Cells (MSCs) Plus Standard of Care in Patients With Anthracycline-Associated Cardiomyopathy

Statistical analyses of safety will be descriptive.

The comparison will be between the two groups of patients.

As regards statistical analyses, the results of the trial will be displayed in table format. Will provide confidence intervals of the differences in change from baseline between each investigational group and the control group. If both investigation groups are significant at the p \< .05 level, then the two investigational drugs can be compared using a gatekeeping procedure. These intervals and the associated p-values will be calculated using two-sample t-tests, with no adjustments for multiple comparisons.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Neoplasms

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Infections

Skin and Connective Tissue Diseases

Rare Diseases

Carcinoma

Adenocarcinoma

Recurrence

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma, Transitional Cell

Virus Diseases

Measles

Cystadenocarcinoma, Serous

Adenocarcinoma, Clear Cell

Adenocarcinoma, Mucinous

Cystadenocarcinoma

Brenner Tumor

Carcinoma, Endometrioid

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Cystic, Mucinous, and Serous

Endometrial Neoplasms

Uterine Neoplasms

Neoplasms, Fibrous Tissue

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Ovarian Cancer

Ovarian Epithelial Cancer

Transitional Cell Carcinoma

Fallopian Tube Cancer

Adenocarcinoma of the Appendix

Brenner Tumor of Ovary

Micronutrients

Anti-Infective Agents

All Drugs and Chemicals

Iodine

Patients receive oncolytic measles virus encoding thyroidal sodium iodide symporter IP over 30 minutes on day 1 of cycle 1 and MV-NIS infected MSC (if MSC are not available, MV-NIS may be given alone) IP over 30 minutes of subsequent cycles. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter

Clinical Trials Referral Office

Evanthia Galanis, M.D.

This phase I/II trial studies the side effects and best dose of oncolytic measles virus encoding thyroidal sodium iodide symporter (MV-NIS) infected mesenchymal stem cells and to see how well it works in treating patients with ovarian, primary peritoneal or fallopian tube cancer that has come back. Mesenchymal stem cells may be able to carry tumor-killing substances directly to ovarian, primary peritoneal and fallopian tube cancer cells.

PRIMARY OBJECTIVES:

I. To determine the maximally tolerated dose (MTD) of intraperitoneal administration of an Edmonston's strain measles virus genetically engineered to produce sodium iodine symporter (NIS) (measles virus \[MV\]-NIS) in patients with recurrent ovarian cancer, delivered by adipose tissue derived mesenchymal stem cells (MSC). (Phase I) II. To assess the 12 month overall survival of patients treated with this regimen. (Phase II)

SECONDARY OBJECTIVES:

I. To assess the tolerability of this regimen. (Phase II) II. To assess the 4 month progression free survival of patients treated with this regimen. (Phase II) III. To assess the response rate, progression-free survival, and overall survival of patients treated with this regimen. (Phase II)

TRANSLATIONAL OBJECTIVES:

I. To assess the time course of viral gene expression and virus elimination and biodistribution of virally infected cells at various time points after infection with MV-NIS versus MSC delivered MV-NIS using single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging. (Phase II) II. To assess viremia, viral replication, and measles virus shedding/persistence following intraperitoneal administration. (Phase II) III. To assess humoral and cellular immune response to the injected virus. (Phase II) IV. To assess in a preliminary fashion the development of antitumor immune response. (Phase II)

OUTLINE: This is a phase I, dose-escalation study followed by phase II study.

Patients receive oncolytic measles virus encoding thyroidal sodium iodide symporter intraperitoneally (IP) over 30 minutes on day 1 of cycle 1 and MV-NIS infected mesenchymal stem cells (MSC) (if MSC are not available, MV-NIS may be given alone) IP over 30 minutes of subsequent cycles. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for up to 5 years.

MV-NIS Infected Mesenchymal Stem Cells in Treating Recurrent Ovarian, Primary Peritoneal or Fallopian Tube Cancer

Phase I/II Trial of Intraperitoneal Administration of Adipose Tissue Derived Mesenchymal Stem Cells Infected With a NIS-Expressing Derivative Manufactured From a Genetically Engineered Strain of Measles Virus in Patients With Recurrent Ovarian Cancer

Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures will be carried out using Spearman's coefficients, chi squared tests, Wilcoxon rank-sum tests, Kaplan-Meier curves, and Cox proportional hazards models, where appropriate.

Will be defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients).

All adverse events (overall, and by dose-level) will be tabulated and summarized. The grade 3+ adverse events will also be described and summarized in a similar fashion.

Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Ninety-five percent binomial confidence intervals for the true success proportion will be calculated.

Will be defined as complete response or partial response.

Kaplan-Meier survival curves and logrank tests will be used to estimate the progression-free time distributions of the study patients and study patient subsets defined by disease and/or correlative characteristics.

The distribution of survival time will be estimated using Kaplan-Meier survival curves and logrank tests. In addition, comparisons of overall survival in patients treated with oncolytic measles virus encoding thyroidal sodium iodide symporter (MV-NIS)/mesenchymal stem cells (MSC) will be made to patients enrolled on the prior MV-carcinoembryonic antigen (CEA) and MV-NIS trial in an exploratory manner.

The distribution of progression-free survival will be estimated using Kaplan-Meier survival curves and logrank tests. In addition, comparisons of overall progression free survival in patients treated with MV-NIS/MSC will be made to patients enrolled on the prior MV-CEA and MV-NIS trial in an exploratory manner.

Mayo Clinic

Blood and Lymph Conditions

Immune System Diseases

Syndrome

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Leukemia, Lymphocytic, Chronic, B-Cell

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Hodgkin Disease

Primary Myelofibrosis

Lymphoma, Non-Hodgkin

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Bone Marrow Diseases

Leukemia, B-Cell

Chronic Disease

Myeloproliferative Disorders

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Graft Versus Host Disease

Lymphosarcoma

Chronic Lymphocytic Leukemia

Chronic Myeloid Leukemia

Hodgkin Lymphoma

Acute Graft Versus Host Disease

Chronic Myeloproliferative Disorders

Antineoplastic Agents

Antirheumatic Agents

Dermatologic Agents

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Melphalan

Cyclosporine

Cyclosporins

Lenograstim

Mycophenolic Acid

Dimethyl Sulfoxide

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antimetabolites

Enzyme Inhibitors

Clotrimazole

Miconazole

Antifungal Agents

Calcineurin Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antitubercular Agents

REDUCED INTENSITY CONDITIONING (RIC):

Flu/Cy/TBI: Patients receive cyclophosphamide IV over 2 hours on day -6 and fludarabine phosphate IV on days -6 to -2 and undergo total-body irradiation on day -1.

Flu/Mel: Patients receive fludarabine daily on days -5 to -2, a single dose of melphalan on day -2, and ATG on day -3 and day-2.

GVHD PROPHYLAXIS: Patients receive cyclosporine PO or IV over 2 hours every 12 hours on beginning on days -5 to 100 with taper beginning on day 100 and mycophenolate mofetil IV or PO BID on days -5 to 100.

TRANSPLANT: Patients undergo a co-transplantation of an intra-osseous umbilical cord blood transplantation and a mesenchymal stem cell transplantation on day 0.

All patients will receive a single IV dose of 50 mg/kg of cyclophosphamide on day -6

cyclophosphamide

Given by IV during prep at 40mg/m2 for 5 days

fludarabine phosphate

Undergo single fraction of reduced intensity conditioning (RIC) regimen of 200 cGy TBI without shielding on day -1

total-body irradiation

Initiated in patients on the day -5. Cyclosporine will be administered orally or intravenously at 2 mg/kg/dose every 12 hours for 2-hour period. Cyclosporine will continue until day +100

cyclosporine

Given at 1g intravenously or orally twice daily from day -5 to +100, or as clinically indicated.

mycophenolate mofetil

Following RIC, on day T+0, dimethylsulphoxide will be removed from the cord blood cells and given as transplant.

umbilical cord blood transplantation

The total dosage of hMSC will be 2x10\^6cells/kg (+/-20%).

mesenchymal stem cell transplantation

Leland Metheny, MD

This clinical trial studies intra-osseous donor umbilical cord blood and mesenchymal stromal cell co-transplant in treating patients with hematologic malignancies. Giving low doses of chemotherapy and total-body irradiation before a co-transplant of donor umbilical cord blood and mesenchymal stromal cells into the bone (intra-osseous) helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil at the time of transplant may stop this from happening.

PRIMARY OBJECTIVES:

I. To estimate the feasibility of combining intra-osseous umbilical cord blood (UCB) hematopoietic stem cells and human mesenchymal stromal cells (hMSC) following reduced intensity conditioning (RIC).

SECONDARY OBJECTIVES:

I. To estimate the time to engraftment of intra-osseous (IO) UCB transplant combined with hMSC following RIC.

II. To estimate the safety profile of IO UBC transplant combined with hMSC.

OUTLINE:

REDUCED INTENSITY CONDITIONING: Patients receive cyclophosphamide intravenously (IV) over 2 hours on day -6 and fludarabine phosphate IV on days -6 to -2 and undergo total body irradiation (TBI) on day -1.

GRAFT-VERSUS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive cyclosporine orally (PO) or IV over 2 hours every 12 hours on beginning on days -5 to 100 with taper beginning on day 100 and mycophenolate mofetil IV or PO twice daily (BID) on days -5 to 100.

TRANSPLANT: Patients undergo intra-osseous UCB and hMSC co-transplant on day 0.

After completion of study treatment, patients are followed up at days 28 and 100, and then at 6, 9, and 12 months.

Intra-Osseous Co-Transplant of UCB and hMSC

Intra-osseous Co-transplant of Cord Blood and Mesenchymal Stromal Cells: A Feasibility Study

Primary graft failure is defined by \<10% BM cellularity in bone marrow biopsies. Failure in more than 30% of patients will indicate unfeasibility of treatment

Primary graft failure is defined by \<500 ANC cell/ul in bone marrow biopsies. Failure in more than 30% of patients will indicate unfeasibility of treatment

Primary graft failure is defined by hematopoietic recovery with \<10% donor cell chimerism. Failure in more than 30% of patients will indicate unfeasibility of treatment

Primary graft failure is defined by hematopoietic recovery with \<40% donor cell chimerism. Failure in more than 30% of patients will indicate unfeasibility of treatment

The rate of neutrophil recovery and median time of recovery will be estimated using the methods of Kaplan and Meier.

The rate of platelet recovery and median time of recovery will be estimated using the methods of Kaplan and Meier.

The median time of neutrophil recovery will be estimated using the methods of Kaplan and Meier.

The median time of platelet recovery will be estimated using the methods of Kaplan and Meier.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Donor Bone Marrow Derived Mesenchymal Stem Cells in Controlling Heart Failure in Patients With Cardiomyopathy Caused by Anthracyclines	NCT02962661	Cardiomyopathy Heart Failure Hematopoietic a... Malignant Solid...	Best Practice Laboratory Biom... Mesenchymal Ste... Mesenchymal Ste...	18 Years - 80 Years	M.D. Anderson Cancer Center
MV-NIS Infected Mesenchymal Stem Cells in Treating Recurrent Ovarian, Primary Peritoneal or Fallopian Tube Cancer	NCT02068794	Fallopian Tube ... Fallopian Tube ... Fallopian Tube ... Fallopian Tube ... Fallopian Tube ... Fallopian Tube ... Malignant Ovari... Ovarian Clear C... Ovarian Endomet... Ovarian Mucinou... Ovarian Seromuc... Ovarian Serous ... Ovarian Transit... Ovarian Undiffe... Primary Periton... Recurrent Fallo... Recurrent Ovari... Recurrent Prima...	Laboratory Biom... Mesenchymal Ste... Oncolytic Measl...	18 Years -	Mayo Clinic
Intra-Osseous Co-Transplant of UCB and hMSC	NCT02181478	Acute Lymphobla... Acute Myelogeno... Myelodysplastic... Myelofibrosis Relapsed Non-Ho... Refractory Non-... Hodgkin Lymphom... Refractory Hodg... Relapsed Chroni... Refractory Chro... Lymphoid Malign... Chronic Myeloge...	cyclophosphamid... fludarabine pho... total-body irra... cyclosporine mycophenolate m... umbilical cord ... mesenchymal ste...	18 Years - 75 Years	Case Comprehensive Cancer Center

Spots Global Cancer Trial Database for mesenchymal stem cell transplantation