Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Rare Diseases

Syndrome

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

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

Hematologic Neoplasms

Anti-Infective Agents

Dermatologic Agents

Antibodies

Cyclosporine

Cyclosporins

Immunoglobulins

Immunoglobulins, Intravenous

Mesna

Participant with high-risk hematologic malignancies undergoing Hematopoietic Cell Transplantation, who do not have a suitable Human Leukocyte Antigen -matched related/sibling donor, Matched Unrelated Donor or Killer immunoglobulin receptors ligand mismatched haploidentical donor identified, will receive a single UCB unit.

Intervention: Preparative Regimen

Patients requiring two UCB units will be eligible for UCBT01 on the observational arm.

Intervention: Preparative Regimen

Fludarabine (75 mg/m2), fractionated total body irradiation (TBI) (12.0 Gy), and cyclophosphamide (120mg/kg) with mesna. Fludarabine will be given once a day at 25 mg/m2 for three days on day -10 to day -8, TBI will be given twice a day at 150 cGy for four days on day -7 to day -4, and cyclophosphamide will be given once a day for at 60mg/kg for two days on day -3 and day -2.

Post-transplantation immunosuppression with cyclosporine and MMF will begin on day -3. Cord Blood infusion will occur on day 0 and G-CSF will start on day +1.

Amr Qudeimat, 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), matched unrelated donor (MURD) or killer-immunoglobulin receptors (KIR) ligand mismatched haploidentical donor identified, will receive an umbilical cord blood transplantation (UCBT) using a myeloablative preparative regimen.

The preparative regimen includes fludarabine (75 mg/m2), fractionated total body irradiation (TBI) (10.0 Gy), and cyclophosphamide (120mg/kg) with mesna. Fludarabine will be given once a day at 25 mg/m2 for three days on day -10 to day -8, TBI will be given twice a day at 150 cGy for four days on day -7 to day -4, and cyclophosphamide will be given once a day for at 60mg/kg for two days on day -3 and day -2. Post-transplantation immunosuppression with cyclosporine and MMF will begin on day -3. Cord Blood infusion will occur on day 0 and G-CSF will start on day +1.

The primary objectives is to estimate the event-free survival (EFS) at one-year post-transplant for research participants with high-risk hematologic malignancies undergoing hematopoietic cell transplantation (HCT) using single unit umbilical cord blood (UCB).

Secondary objectives are:

* Describe the clinical outcome of patients undergoing a double unit UCBT.
* Estimate the incidence and severity of acute and chronic graft versus host disease (GVHD) of patients enrolled in the research arm.
* Estimate the incidence and time to neutrophil and platelet engraftment among patients enrolled in the research arm.
* Estimate the incidence of transplant related mortality (TRM) and transplant related morbidity in the first 100 days after transplantation among patients enrolled in the research

Exploratory Objectives are:

* Assess the relationship between pre-transplant minimal residual disease (MRD) with transplant outcomes.
* Record immune reconstitution parameters, including chimerism analysis, quantitative lymphocyte subsets, T cell receptor excision circle (TREC) and spectratyping. Immunophenotyping and functional assays of T, B and NK cells and lymphocytes will also be evaluated.
* Evaluate the determinants of engraftment.

Umbilical Cord Blood Transplantation In Patients With Hematologic Malignancies Using A Myeloablative Preparative Regimen

Estimate EFS for research participants at one-year post transplant by using single unit umbilical cord blood. The event is defined as relapse, graft failure, death due to any cause. The number of participants who did not experience any of those events (relapse, graft failure, death due to any cause) at year 1 post-transplant was given.

For patients enrolled in the observational arm (undergoing a double unit UCBT), the number of patients engrafted was given.

The number of observational arm patients who relapsed was given.

The number of observational arm patients who died was given.

The number of patients with TRM within the first 100 days post transplant was given.

The number of participants with incidence of acute GVHD by grade was given. Participants are graded on a scale from 1 to 4, with 1 being mild and 4 being severe.

Due to the small sample size, cumulative incidence analysis was not done. The incidence of chronic GVHD was evaluated using NIH Consensus Global Severity Scoring. The number of patients with incidence of chronic GVHD by severity was provided.

Platelet engraftment was defined as platelet count ≥20,000/mm\^3 for 3 consecutive tests performed on different days with no platelet transfusions in the preceding 7 days. Neutrophil engraftment will be defined as achieving ANC ≥ 500/mm3 for 3 consecutive tests performed on different days with evidence of donor cell engraftment. Descriptive statistics are provided.

TRM is death occurring in patients in continuous complete remission. The numbers of patients with TRM was given.

Any patient who had adverse events listed either as probable or definite in the first 100 days post-transplant are counted as transplant related morbidity. The number of patients with transplant-related morbidity was given.

The Hartwell Foundation

Assisi Foundation

St. Jude Children's Research Hospital

Participant with high-risk hematologic malignancies undergoing Hematopoietic Cell Transplantation, who do not have a suitable Human Leukocyte Antigen -matched related/sibling donor, Matched Unrelated Donor or Killer immunoglobulin receptors ligand mismatched haploidentical donor identified, will receive a single UCB unit.

Intervention: Preparative Regimen

Preparative Regimen: Fludarabine (75 mg/m2), fractionated total body irradiation (TBI) (12.0 Gy), and cyclophosphamide (120mg/kg) with mesna. Fludarabine will be given once a day at 25 mg/m2 for three days on day -10 to day -8, TBI will be given twice a day at 150 cGy for four days on day -7 to day -4, and cyclophosphamide will be given once a day for at 60mg/kg for two days on day -3 and day -2.

Post-transplantation immunosuppression with cyclosporine and MMF will begin on day -3. Cord Blood infusion will occur on day 0 and G-CSF will start on day +1.

Research Arm

Patients requiring two UCB units will be eligible for UCBT01 on the observational arm.

Intervention: Preparative Regimen

Preparative Regimen: Fludarabine (75 mg/m2), fractionated total body irradiation (TBI) (12.0 Gy), and cyclophosphamide (120mg/kg) with mesna. Fludarabine will be given once a day at 25 mg/m2 for three days on day -10 to day -8, TBI will be given twice a day at 150 cGy for four days on day -7 to day -4, and cyclophosphamide will be given once a day for at 60mg/kg for two days on day -3 and day -2.

Post-transplantation immunosuppression with cyclosporine and MMF will begin on day -3. Cord Blood infusion will occur on day 0 and G-CSF will start on day +1.

Observation Arm

Observational Arm

Total

Age, Continuous

Sex: Female, Male

Race/Ethnicity, Customized

Event Free Survival (EFS) for Research Participants

Number of Observational Arm Participants Engrafted

Number of Observational Arm Patients Who Relapsed

Number of Deaths of Observational Arm Patients

Patients requiring two UCB units will be eligible for UCBT01 on the observationalal arm.

Intervention: Preparative Regimen

Preparative Regimen: Fludarabine (75 mg/m2), fractionated total body irradiation (TBI) (12.0 Gy), and cyclophosphamide (120mg/kg) with mesna. Fludarabine will be given once a day at 25 mg/m2 for three days on day -10 to day -8, TBI will be given twice a day at 150 cGy for four days on day -7 to day -4, and cyclophosphamide will be given once a day for at 60mg/kg for two days on day -3 and day -2.

Post-transplantation immunosuppression with cyclosporine and MMF will begin on day -3. Cord Blood infusion will occur on day 0 and G-CSF will start on day +1.

Number of Observational Arm Patients With Transplant-related Mortality (TRM)

Patients requiring two UCB units will be eligible for UCBT01 on the observational arm.

Intervention: Preparative Regimen Preparative Regimen: Fludarabine (75 mg/m2), fractionated total body irradiation (TBI) (12.0 Gy), and cyclophosphamide (120mg/kg) with mesna. Fludarabine will be given once a day at 25 mg/m2 for three days on day -10 to day -8, TBI will be given twice a day at 150 cGy for four days on day -7 to day -4, and cyclophosphamide will be given once a day for at 60mg/kg for two days on day -3 and day -2.

Post-transplantation immunosuppression with cyclosporine and MMF will begin on day -3. Cord Blood infusion will occur on day 0 and G-CSF will start on day +1.

Number of Participants With Acute GVHD

Number of Participants With Chronic GVHD

Days to Platelets ≥20,000

Days to ANC ≥500

Those patients who did not reach engraftment are not included in the results provided below.

Time to Engraftment of Research Arm Participants

Incidence of Transplant-related Mortality (TRM)

The Number of Participants With Transplant-related Morbidity

Overall Study

Immune System Diseases

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Lymphosarcoma

Cytarabine

Venetoclax

Rituximab

Abatacept

Plerixafor

Treosulfan

Preparative chemotherapy before allogeneic HSCT

* Fludarabin
* Cytarabine
* Venetoclax
* Daratumomab
* Vecanoid
* treosulfan
* fludarabine
* thiophosphomide
* Venetoclax
* Plerixafor
* abatacept
* tocilizumab
* rituximab
* HSCT from the haploidentical donor, ex vivo depleted of alpha/beta T lymphocytes

Preparative chemotherapy before allogeneic HSCT

* Fludarabin
* Cytarabine
* Venetoclax
* Daratumomab
* Vecanoid Condition
* treosulfan
* fludarabine
* thiophosphomide
* Venetoclax
* Plerixafor GVHD prophylaxis
* abatacept
* tocilizumab
* rituximab
* HSCT from the haploidentical donor, ex vivo depleted of alpha/beta T lymphocytes

Preparative regimen

Larisa Shelikhova

Zhanna Shekhovtsova

Zhanna Shekhovtsova, MD

Eugene Pashanov, PhD

Michael Maschan, PhD

The purpose of this study is to evaluate the safety and efficiency of personalized targeted therapy in combination with high-dose chemotherapy as part of a preparative regimen before T-depleted allogeneic hematopoietic stem cell transplantation in children with chemoresistant acute leukemias

The outcome of hematopoietic stem cell transplantation (HSCT) in a cohort of children with chemorefractory leukemia is poor. The incidence of relapse exceeds 50% and survival varies from 10 to 40%. Additional attempts at remission induction with various combinations of chemotherapy are unlikely to improve the outcome and will contribute to toxicity.

The hypothesis of the study is that personalized targeted therapy combined with high-dose chemotherapy may improve the outcome of allogeneic HSCT in a cohort of pediatric patients with refractory leukemia.

Bcl-2, CD38, CD184 were chosen as potential targets due to frequent expression in pediatric acute leukemias, availability of marketed targeted therapies venetoclax, daratumumab and prelixafor, and expected non-overlapping toxicity profile of these agents and the conditioning regimen.

Personalized Targeted Preparative Regimen Before T-depleted Allogeneic HSCT in Children With Chemoresistent Acute Leukemias

A Phase I-II Pilot Clinical Trial of Safety and Efficacy of Personalized Targeted Preparative Regimen With Allogeneic TcRαβ/CD19-depleted Hematopoietic Stem Cell Transplantation and Posttransplant Donor T- Cells Infusion in Children With Chemoresistаnt Acute Leukemia.

Proportion of patients with hematologic remission at time points

Proportion of patients with MRD negativity at time points

Proportion of patients with allergic/ anaphylaxis reaction toxicity stage \> 3 according to CTCAE 5.0

Proportion of patients with target molecule on blast cells: CD38 and/or CD 184 and/or Bcl2

Proportion of patients with early immune recovery: T-cell, NK- cell, B-cell \>determined numbers

Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Heart and Blood Diseases

Carcinoma

Carcinoma, Renal Cell

Multiple Myeloma

Neoplasms, Plasma Cell

Lymphoma, Non-Hodgkin

Hodgkin Disease

Neoplasms, Glandular and Epithelial

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Adenocarcinoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Hodgkin Lymphoma

Anti-Arrhythmia Agents

Vasodilator Agents

Analgesics

Alemtuzumab

Pentostatin

Antineoplastic Agents, Immunological

Adenosine

Enzyme Inhibitors

Days - 8 through -6: pentostatin 4 mg/m2/24 hr as a continuous intravenous infusion (CIVI) (total cumulative dose, 12 mg/m2 over 3 days)

Days - 5 through - 1: alemtuzumab 20 mg per dose intravenously over 8 hours daily for 5 doses (total cumulative dose, 100 mg)

Followed by Allogeneic hematopoietic stem cell transplantation, related or unrelated donor, on day 0. Patients also receive cyclosporine intravenous (IV) continuously beginning on day -2, continuing (IV or orally) until day 100, followed by a taper.

Days - 8 through -6: pentostatin 4 mg/m2/24 hr as a continuous intravenous infusion (CIVI) (total cumulative dose, 12 mg/m2 over 3 days)

Days - 5 through - 1: alemtuzumab 20 mg per dose intravenously over 8 hours daily for 5 doses (total cumulative dose, 100 mg)

Infusion of related or unrelated donor peripheral blood progenitor cells on day 0.

Allogeneic hematopoietic stem cell transplantation

Andrew M Yeager, MD

This study tests the hypothesis that a purely immunosuppressive preparative regimen allows engraftment of related or unrelated allogeneic hematopoietic stem cells in subjects with high-risk malignancies, without causing the post-transplant myelosuppression (e.g., neutropenia, thrombocytopenia) that occurs with currently used reduced-intensity (nonmyeloablative) preparative regimens. This study incorporates both safety and efficacy endpoints and evaluates a novel preparative regimen of alemtuzumab plus continuous-infusion pentostatin, two immunosuppressive agents with different mechanisms of action, in recipients of related or unrelated allogeneic hematopoietic stem cell transplantation.

Primary Objectives of the study:

* To determine the efficacy of a preparative regimen of pentostatin and alemtuzumab plus related or unrelated allogeneic peripheral blood stem cell transplantation (PBSCT) in inducing durable donor lymphohematopoietic cell chimerism (defined as at least 50% donor cells in the peripheral blood) by 100 days after PBSCT (day +100) in subjects with high-risk malignancies who are at high risk for morbidity and mortality with conventional intensive pre-transplant conditioning regimens.
* To determine the safety of a preparative regimen of pentostatin and alemtuzumab plus related or unrelated allogeneic PBSCT, as measured by the non-relapse mortality at day +100 in the study subject population.

Pentostatin and Alemtuzumab as a Preparative Regimen for Allogeneic Peripheral Blood Stem Cell Transplantation

Phase II Related or Unrelated Allogeneic Hematopoietic Cell Transplantation for High-Risk Malignancies, Using a Preparative Regimen of Pentostatin (Nipent®) and Alemtuzumab (Campath®)

The number of participants with donor hematopoietic engraftment at day 100 is reported in the data table, and the actuarial probability is calculated using the Kaplan-Meier product-limit estimate statistic, as reported in the statistical analysis section below.

The primary safety outcome is indicated by the number of participants who died at or before Day 100 after transplant for any reason other than relapse of disease (Leukemia, Lymphoma, Hodgkin's disease, Hematologic Neoplasms, Multiple Myeloma, Renal Cell Carcinoma).

National Cancer Institute (NCI)

University of Arizona

Adverse event data was collected and entered into the AZCC database which is password protected. The safety population is defined to be all participants who completed at least 1 day of treatment.

Pentostatin and Alemtuzumab as a Preparative Regimen for Allogeneic \[related or unrelated\] Hematopoietic SCT.

Pentostatin: 4 mg/m2/24 hour IV continuously over 72 hours on days -8 to -6. Alemtuzumab: 20 mg per dose IV over 8 hours on days -5 to -1. Patients then received infusion of related or unrelated donor peripheral blood progenitor cells on day 0. Patients also receive cyclosporine IV continuously beginning on day -2, continuing (IV or orally) until day 100, followed by a taper.

Preparative Regimen of Pentostatin and Alemtuzumab

Age, Categorical

United States

Region of Enrollment

We did not meet criteria to stop the study because of nonrelapse mortality (safety endpoint). However, we stopped accrual to the study because of failure to meet minimal criteria for engraftment (efficacy endpoint).

Andrew M. Yeager, MD

All participants who completed treatment and underwent allogeneic transplant.

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
Umbilical Cord Blood Transplantation In Patients With Hematologic Malignancies Using A Myeloablative Preparative Regimen	NCT01328496	Hematologic Mal... Disorder Relate... Hematopoietic M...	Preparative Reg...	- 21 Years	St. Jude Children's Research Hospital
Personalized Targeted Preparative Regimen Before T-depleted Allogeneic HSCT in Children With Chemoresistent Acute Leukemias	NCT04000698	Refractory Acut... Refractory Acut...	Preparative reg...	- 25 Years	Federal Research Institute of Pediatric Hematology, Oncology and Immunology
Personalized Targeted Preparative Regimen Before T-depleted Allogeneic HSCT in Children With Chemoresistent Acute Leukemias	NCT04000698	Refractory Acut... Refractory Acut...	Preparative reg...	- 25 Years	Federal Research Institute of Pediatric Hematology, Oncology and Immunology
Umbilical Cord Blood Transplantation In Patients With Hematologic Malignancies Using A Myeloablative Preparative Regimen	NCT01328496	Hematologic Mal... Disorder Relate... Hematopoietic M...	Preparative Reg...	- 21 Years	St. Jude Children's Research Hospital
Pentostatin and Alemtuzumab as a Preparative Regimen for Allogeneic Peripheral Blood Stem Cell Transplantation	NCT00698685	Leukemia Lymphoma Hodgkin's Disea... Hematologic Neo... Multiple Myelom... Carcinoma, Rena...	Pentostatin Alemtuzumab Allogeneic hema...	18 Years - 75 Years	University of Arizona
Stem Cell Transplant for Juvenile Myelomonocytic Leukemia (JMML)	NCT00167219	Juvenile Myelom...	Stem Cell Trans... Preparative Reg...	- 18 Years	Masonic Cancer Center, University of Minnesota

Spots Global Cancer Trial Database for preparative regimen