Symptoms and General Pathology

All Conditions

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Syndrome

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

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Neoplasms by Histologic Type

Hematologic Diseases

Bone Marrow Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Adults with Refractory or Relapsed Acute Myelogenous Leukemia (AML) treated with preparative regimen and Intravenous Recombinant Human IL-15 (rhIL-15)

Fludarabine 25 mg/m\^2 x 5 days start day -6, Cyclophosphamide 60 mg/kg x 2 days on day -5 and -4 (\*if \< 4 months from prior transplant, omit day -4 dose)

Preparative Regimen

IL-15 at assigned dose (0.25, 0.5, 0.75 1, 2 and 3 mcg/kg for 3 to 6 patients) intravenously (IV) over 30 minutes once a day beginning day +1 and continuing for 12 doses

Intravenous Recombinant Human IL-15 (rhIL-15)

Jeffrey S Miller, MD

This is a single center, "modified standard design" dose escalation study designed to determine the maximum tolerated, minimum efficacious dose (MTD/MED) of IL-15 (Intravenous Recombinant Human IL-15) and incidence of donor natural killer (NK) cell expansion by day +14 when given after haploidentical donor NK cells in patients with relapse or refractory acute myelogenous leukemia (AML).

Once the MTD/MED for IL-15 is determined, this cohort will be expanded to a total of 19 patients. The primary goal of this extended phase will be to establish a correlation of the clinical endpoint, CRp defined as leukemic clearance (\< 5% marrow blast and no peripheral blood blasts) and neutrophil recovery without platelet recovery, with in vivo expansion.

Patients achieving a complete remission and neutrophil recovery (ANC \> 500) for at least 4 weeks will be considered for allogeneic transplant to prolong remission independent of this study.

All patients, including those who go on to transplant, will be followed to determine disease free survival, treatment related mortality, and time to relapse.

Haploidentical Donor Natural Killer Cell Infusion With IL-15 in Acute Myelogenous Leukemia (AML)

Haploidentical Donor Natural Killer (NK) Cell Infusion With Intravenous Recombinant Human IL-15 (rhIL-15) in Adults With Refractory or Relapsed Acute Myelogenous Leukemia (AML)

Determine the maximum tolerated, minimum efficacious dose (MTD/MED) of recombinant human IL-15; dose limiting toxicity (DLT) occurring during the first 42 days after the NK cell infusion; MED = if 2 of 3 patients or 4 of 6 patients has an in vivo NK cell count \>2500, then dose escalation with cease as it will be in the range of a biologic dose which may achieve the goal of in vivo expansion without pushing IL-15 doses higher to toxicity.

defined by measuring an absolute circulating donor-derived NK cell count of \>100 cells/μl in the patient's peripheral blood by day +14 after the NK cell infusion.

In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation.

defined as leukemia clearance (\< 5% marrow blasts and no peripheral blood blasts) and neutrophil recovery without platelet recovery.

Masonic Cancer Center, University of Minnesota

Immune System Diseases

Leukemia, Myelomonocytic, Juvenile

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Hematologic Neoplasms

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Myeloproliferative Disorders

Chronic Disease

Disease Attributes

Myelodysplastic-Myeloproliferative Diseases

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Graft Versus Host Disease

Lymphosarcoma

Chronic Myeloid Leukemia

Chronic Myeloproliferative Disorders

Myelodysplastic/myeloproliferative Disease

Analgesics

Etoposide

Immunomodulating Agents

Etoposide phosphate

Interleukin-2

Clofarabine

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Enzyme Inhibitors

Analgesics, Non-Narcotic

Antimetabolites

Patients with ALL, CML, JMML, MDS, or NHL with bone marrow relapse after stem cell transplant.

Patients with ALL, CML, JMML , MDS, or NHL with primary induction failure and persistent disease; or participants with relapsed ALL, CML, JMML, MDS, or NHL with persistent disease after re-induction

All participants will receive a 4 day regimen of chemotherapy (clofarabine, cyclophosphamide, and etoposide) followed by an infusion of HLA partially matched family member donor NK cells processed through the use of the investigational CliniMACS device. Interleukin-2 (IL-2) will be given three times per week post-infusion for a minimum of 2 weeks. IL-2 administration will continue until donor NK cells are no longer detectable in the recipient, and, at that time, will be discontinued

NK Cell Infusion

All participants will receive a 4 day regimen of chemotherapy (clofarabine, cyclophosphamide, and etoposide) followed by an infusion of HLA partially matched family member donor NK cells processed through the use of the investigational CliniMACS device. Interleukin-2 (IL-2) will be given three times per week post-infusion for a minimum of 2 weeks. IL-2 administration will continue until donor NK cells are no longer detectable in the recipient, and, at that time, will be discontinued.

Immunotherapy

Miltenyi Biotec CliniMACS device

Interleukin-2 (IL-2)

Wing Leung, MD, PhD

The prognosis of pediatric patients with hematologic malignancies whose disease is primarily refractory or those who experience a chemotherapy resistant bone marrow relapse is extremely poor. When new agents or chemotherapeutic regimens are unable to induce remission in this patient population, hematopoietic stem cell transplant (HSCT) is also a poor alternative. Thus, in this very high risk group, additional attempts at remission induction with various combinations of chemotherapy alone will unlikely improve outcome and will contribute to overall toxicity. Alternative therapies are needed in these patients with chemotherapy resistant disease.

Immunotherapy with natural killer (NK) cell infusion has the potential to decrease toxicity and induce hematologic remission. NK cells can kill target cells, including leukemia cells, without prior exposure to those cells. In patients undergoing allogeneic HSCT, several studies have demonstrated the powerful effect of NK cells against leukemia. Furthermore, NK cell infusions in patients with primary refractory or multiple-relapsed leukemia have been shown to be well tolerated and void of graft-versus-host disease effects. In this high risk group, complete leukemic remission has been observed in several of these patients after NK cell infusion.

With the current technology available at St. Jude, we have developed a procedure to purify NK cells from adult donors. This protocol will assess the safety of chemotherapy and IL-2 administration to facilitate transient NK-cell engraftment in research participants who have chemotherapy refractory hematologic malignancies including acute lymphoblastic leukemia, chronic myelogenous leukemia, juvenile myelomonocytic leukemia, myelodysplastic syndrome, or non-Hodgkin's lymphoma. In this same cohort, we will also intend to explore the efficacy of NK cells infused in those participants who have chemotherapy refractory disease.

This study will evaluate the persistence, phenotype and function of donor NK cells as well as exploring the efficacy of the infusion in research participants with chemotherapy refractory hematologic malignancies.

Pilot Study of Haploidentical Natural Killer Cell Infusions for Poor Prognosis Non-AML Hematologic Malignancies

Assisi Foundation

St. Jude Children's Research Hospital

Graft vs Host Disease

Homologous Wasting Disease

Anti-Infective Agents

Mycophenolic Acid

Tacrolimus

Busulfan

Calcineurin Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antitubercular Agents

Conditioning:

fludarabine 180 mg/m2 busulfan 8-14 mg/kg per os

GVHD prophylaxis:

cyclophosphamide 50 mg/kg day+3, +4 tacrolimus 0.03 mg/kg from day+5 to 100 mycophenolate mofetil 30 mg/kg from day+5 to 35

Conditioning:

fludarabine 180 mg/m2 busulfan 8-14 mg/kg per os ruxolitinib 5 mg tid days -7 to -2

GVHD prophylaxis:

cyclophosphamide 50 mg/kg day+3, +4 ruxolitinib 5 mg tid days +5 to +21 ruxolitinib 5 mg bid days +22 to +150

Ruxolitinib administered during conditioning 5 mg tid before allogeneic hematopoietic stem cell transplantation, 5 mg tid days 5-21 and 5 mg bid days 22-150 after transplantation instead of tacrolimus and MMF.

Ruxolitinib

Tacrolimus 0.03 mg/kg adjusted to concentrations 5-15 ng/ml from day+5 to +100

Mycophenolate mofetil 30 mg/kg from day +5 to +35

Mycophenolate Mofetil

This is multicenter investigator-initiated randomized open-label phase II clinical trial to compare prophylaxis of graft versus host disease treated with tacrolimus and mycophenolate mofetil versus ruxolitinib after post-transplant cyclophosphamide.

In total 128 patients will be included in the study. After inclusion into the study and performing of transplantation patients will be randomized in 1:1 proportion in two arms (64 patients per arm): arm A will include patients who will be treated with cyclophosphamide and ruxolitinib for GVHD prophylaxis; arm B will include patients who will be treated with cyclophosphamide, tacrolimus and MMF for GVHD prophylaxis. After the end of the treatment patients will be followed-up during two years.

PTCy and Ruxolitinib vs PTCy, Tacrolimus and MMF in MUD and Haploidentical HSCT

A Randomized, Multicenter, Open-label Phase II Trial to Compare Prophylaxis of Graft Versus Host Disease With Tacrolimus and Mycophenolate Mofetil Versus Ruxolitinib After Post-transplant Cyclophosphamide

Proportion of patients with acute GVHD II-IV grade

Cumulative incidence of patients with mortality without hematological relapse of malignancy

Cumulative incidence of patients with relapse

Cumulative incidence of patients with moderate and severe chronic GVHD according to NIH 2015 criteria

Kaplan-Meier estimate of death from all causes

Kaplan-Meier estimate of death or relapse

Toxicity assessment is based on NCI CTC AE 5.0 grades. Veno-occlusive disease incidence and severity assessment is based on EBMT criteria 2016. Transplant-associated microangiopathy incidence assessment is based on Cho et al. criteria. All toxicity measurements will be aggregated as severity scores.

Cumulative incidence of patients with primary or secondary graft failure defined by the absence of donor chimerism.

Number of patients with bacteremia before engraftment, bacteremia after engraftment, severe sepsis (presence of multiple organ failure), pneumonia, soft tissue infection, invasive mycosis (probable or proven invasive aspergillosis, candidaemia, zygomycosis), reactivation of cytomegalovirus, other opportunistic viral infections

St. Petersburg State Pavlov Medical University

RM Gorbacheva Research institute scientific director

Control group of all eligible patients who received an HSCT from a haploidentical donor without ATIR administration between 1 January 2006 and 30 June 2013

Control group of eligible patients who received an HSCT from a fully matched unrelated donor between 1 January 2010 and 31 December 2012

Control group of eligible patients who received an HSCT from a 1-locus mismatched unrelated donor between 1 January 2010 and 31 December 2012

Control group of eligible patients who received a double umbilical cord blood transplantation between 1 January 2010 and 31 December 2012

Jeroen Rovers, MD

Study CR-AIR-006 is a part of the ATIR clinical development plan and will provide control data for patients treated with ATIR in clinical studies (e.g. study CR-AIR-007).

Transplant-Related Mortality in Patients Undergoing a Peripheral Blood Stem Cell Transplantation or an Umbilical Cord Blood Transplantation

An Observational Cohort Study on Transplant-Related Mortality in Patients Receiving Either a Hematopoietic Stem Cell Transplantation Without ATIR or an Umbilical Cord Blood Transplantation

Kiadis Pharma

Diseases and Abnormalities at or Before Birth

Nutritional and Metabolic Diseases

Nervous System Diseases

Gland and Hormone Related Diseases

Anemia, Sickle Cell

Anemia

Metabolic Diseases

Thalassemia

Immunologic Deficiency Syndromes

Anemia, Aplastic

Metabolism, Inborn Errors

Adrenoleukodystrophy

Genetic Diseases, Inborn

Sickle Cell Anemia

Aplastic Anemia

X-linked Adrenoleukodystrophy

Adrenomyeloneuropathy

The CliniMACS CD34 Reagent System is a medical device that is used in vitro to select and enrich CD34+ cells from heterogeneous hematologic cell populations for transplantation in cases where this is clinically indicated.

CliniMACS CD34 Reagent System

Erin Arbuckle

Joanne Kurtzberg, MD

The objective of this study is to make T-cell depleted stem cells from a family member who is a half match (haplo-identical) available on an expanded access basis to patients receiving one or two unrelated cord blood transplants who are at a higher risk of not engrafting in a safe amount of time. The purpose of the related stem cells is the give the bone marrow a "jump start" towards recovery. Ultimately, the cord blood cells will grow and permanently rescue the bone marrow.

The primary purpose of the study is to provide expanded access of T-cell depleted haplo-identical stem cells for patients receiving allogeneic transplantation from a related haplo-identical donor and an unrelated, umbilical cord blood (UUCB) unit(s) for the treatment of high risk malignancies and non-malignant disorders. The T-cell depleted haplo-identical stems cells are intended to facilitate early, short-term myeloid engraftment with the primary goal of minimizing early infections and other non-relapse mortality while the UUCB cells engraft as the durable and permanent graft. Patients with high risk or refractory malignancies, or non-malignant disorders amenable to stem cell transplantation therapy but lacking conventional related or unrelated donors will be eligible for this protocol.

Expanded Access to T-cell Depleted Haplo-Identical Stem Cells for Patients Receiving Haplo-Identical and Unrelated Cord Blood Transplants

A Compassionate Release Protocol: Expanded Access to T-cell Depleted Haplo-Identical Stem Cells for Patients Receiving Allogeneic Transplantation Using a Related Haplo-Identical Donor and Unrelated, Umbilical Cord Blood Donor(s) for the Treatment of High Risk Malignancies or Non-Malignant Disorders Requiring Allogeneic Transplantation

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Haploidentical Donor Natural Killer Cell Infusion With IL-15 in Acute Myelogenous Leukemia (AML)	NCT01385423	Acute Myelogeno... Myelodysplastic...	Preparative Reg... Intravenous Rec...	18 Years -	Masonic Cancer Center, University of Minnesota
Pilot Study of Haploidentical Natural Killer Cell Infusions for Poor Prognosis Non-AML Hematologic Malignancies	NCT00697671	Acute Lymphobla... Chronic Myeloge... Juvenile Myelom... Myelodysplastic... Non-Hodgkin's L...	NK Cell Infusio... Immunotherapy Miltenyi Biotec... Interleukin-2 (... Clofarabine Cyclophosphamid... Etoposide	- 18 Years	St. Jude Children's Research Hospital
PTCy and Ruxolitinib vs PTCy, Tacrolimus and MMF in MUD and Haploidentical HSCT	NCT04669210	Graft-versus-ho... Stem Cell Trans... Acute Myeloid L... Acute Lymphoid ...	Ruxolitinib Tacrolimus Mycophenolate M...	18 Years - 70 Years	St. Petersburg State Pavlov Medical University
Transplant-Related Mortality in Patients Undergoing a Peripheral Blood Stem Cell Transplantation or an Umbilical Cord Blood Transplantation	NCT02188290	Acute Myeloid L... Acute Lymphobla... Myelodysplastic...		18 Years - 65 Years	Kiadis Pharma
Expanded Access to T-cell Depleted Haplo-Identical Stem Cells for Patients Receiving Haplo-Identical and Unrelated Cord Blood Transplants	NCT01881334	Hematologic Mal... Inborn Errors o... Immune Deficien...	CliniMACS CD34 ...	- 65 Years	Duke University
Transplant-Related Mortality in Patients Undergoing a Peripheral Blood Stem Cell Transplantation or an Umbilical Cord Blood Transplantation	NCT02188290	Acute Myeloid L... Acute Lymphobla... Myelodysplastic...		18 Years - 65 Years	Kiadis Pharma

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