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

Antirheumatic Agents

All Drugs and Chemicals

Anti-Infective Agents

Analgesics

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Aldesleukin

Interleukin-2

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Analgesics, Non-Narcotic

Fludarabine Day -6 to -2 and Cyclophosphamide Day -5 and -4. On Day 0 PNK-007 at 4 varying dose levels followed by Human recombinant Interleukin-2 (rhIL-2) every other day, Day 0 to Day 10.

PNK-007

Human recombinant Interleukin-2 (rhIL-2)

Solveig Ericson, MD

This study will find the highest acceptable treatment dose of cord blood, culture expanded natural killer (NK) cells, a kind of immune cell, in patients with relapsed and/or refractory acute myeloid leukemia.

The NK cells will be given with chemotherapy and Recombinant human interleukin 2 (rhIL-2) to help the NK cells expand in the body. The safety of this treatment will be studied and researchers want to learn if NK cells will help in treating the AML.

The primary objective of the study is to assess safety and determine the maximum tolerated dose of PNK-007 in subjects with relapsed and/or refractory acute myeloid leukemia (AML). The secondary objective is to explore the potential clinical efficacy by day 42.

Treatment plan includes conditioning with cyclophosphamide and fludarabine. PNK-007 will administered IV followed by a total of six Recombinant human interleukin 2 (rhIL-2) injections to support the NK cells in the body.

Subjects will be followed for up to 24 months.

A Safety Study of Human Cord Blood Derived, Culture Expanded Natural Killer Cell (PNK-007) Infusion With Subcutaneous Recombinant Human IL-2 (rhIL-2) in Adults With Relapsed and/or Refractory Acute Myeloid Leukemia (AML)

A Phase 1, Multicenter, Open-Label, Dose Escalating Safety Study of Human Cord Blood Derived, Culture Expanded Natural Killer Cell (PNK-007) Infusion With Subcutaneous Recombinant Human IL-2 (RHIL-2) in Adults With Relapsed and/or Refractory Acute Myeloid Leukemia (AML).

Number and severity of adverse events within 28 days of administration.

The maximum dose safely administered for the treatment of patients with AML.

CRp is defined as leukemia clearance (\< 5% marrow blasts and no circulating peripheral blasts) and neutrophil recovery but with incomplete platelet recovery.

CR is defined as leukemia clearance (\< 5% marrow blasts, no circulating peripheral blasts) in conjunction with normal values for absolute neutrophil count (\> 1000/μL) and platelet count (\> 100,000/μL), and independence from red cell transfusion.

Celularity Incorporated

Cytarabine

Antimetabolites

Antiviral Agents

Dose-escalation Phase

* Schedule A:
* Schedule B:

Expansion Phase

* Schedule A:
* Schedule B:

Dose-escalation Phase

* Schedule A: vosaroxin injection (dose-escalation from 10 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (24-hour CIV infusion of 400 mg/m2/day × 5 days)
* Schedule B: vosaroxin injection (dose-escalation from 70 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (2-hour intravenous \[IV\] infusion of 1 g/m2/day × 5 days)

Expansion Phase The MTD determined in the dose-escalation phase was used in the expansion phase.

* Schedule A: 80 mg/m2 vosaroxin on Days 1 and 4 in combination with cytarabine (24-hour CIV infusion at 400 mg/m2/day × 5 days)
* Schedule B: 90 mg/m2 vosaroxin (dose-escalation) on Days 1 and 4 in combination with cytarabine (2 hour IV infusion at 1 g/m2/day × 5 days)

Voreloxin injection and cytarabine

Sunesis Medical Monitor, MD

This study will evaluate the safety and tolerability of voreloxin (vosaroxin) injection in combination with cytarabine in patients with relapsed or refractory acute myeloid leukemia.

An open-label, Phase 1b/2 study using a dose-escalation design with expansion at the maximum tolerated dose (MTD) using 2 dosing schedules:

During the Schedule A dose-escalation phase, patients with relapsed or refractory acute myeloid leukemia (AML) enrolled in cohorts of at least 3 patients to identify the MTD. Begin with a starting dosing regimen of vosaroxin of 10 mg/m2 on Days 1 and 4 of each cycle in combination with a 24-hour continuous intravenous (CIV) infusion of cytarabine 400 mg/m2/day × 5 days. If none of the 3 patients or 1 of 6 patients experience a dose-limiting toxicity (DLT) at the vosaroxin starting dose, dose-escalate vosaroxin. If 2 of 6 patients experienced a DLT at the vosaroxin starting dose, reduce the dose of cytarabine to reduced to 200 mg/m2 (only case in which the cytarabine could have been reduced). The vosaroxin dose escalated following a modified Fibonacci schema.

For Schedule B dose-escalation phase, patients with relapsed or refractory AML enrolled in cohorts of at least 3 patients to identify the MTD. Begin with a starting dose regimen of vosaroxin of 70 mg/m2 on Days 1 and 4 in combination with cytarabine as a 2-hour infusion of 1 g/m2/day × 5 days. No reductions of cytarabine allowed in Schedule B. If none of the 3 patients or 1 of 6 patients experienced a DLT in the first cohort of Schedule B, escalate the dose of vosaroxin. If DLTs occurred in 2 of 6 patients during the starting dose, reduce the vosaroxin dose to 50 mg/m2.

For both Schedules, the highest dose at which fewer than 2 of 6 patients experienced a DLT during induction became the MTD and the recommended future dose.

Once the MTD of vosaroxin was determined for Schedule A, first relapse patients were enrolled in the expansion phase at that dose level to obtain additional safety and efficacy information. When the MTD of vosaroxin was determined for Schedule B, first relapse patients and patients with primary refractory disease were enrolled in the expansion phase at that dose level to characterize the safety and efficacy profile in this population.

Safety and Tolerability Study of Voreloxin and Cytarabine Combination in Acute Myeloid Leukemia in Humans

Phase 1b/2, Open-Label, Multicenter, Dose-Escalating, Clinical Study of the Safety, Tolerability, and PK and PD Profiles of Voreloxin Injection in Combination With Cytarabine in Patients With Relapsed or Refractory AML

Patients were treated in cohorts with escalating doses of vosaroxin administered in combination with cytarabine in Schedule A, and with vosaroxin in escalating doses in Schedule B. For both Schedules, the highest dose at which fewer than 2 of 6 (\<0.33) patients experienced a dose-limiting toxicity (DLT) during induction became the MTD and the recommended future dose.

Complete remission (CR) plus CR with incomplete platelet recovery (CRp) per The IWG criteria for remission modified by Sunesis, assessed by investigator.

CR is defined as \>1000 Neutrophils (ul), \>100,000 Platelets (uL) and \<5 BM Blasts (%); CRp is defined as \>1000 Neutrophils (ul), \<=100,000 Platelets (uL) and \<5 BM Blasts (%); CRi is defined as \>1000 Neutrophils (ul), \<100,000 Platelets (uL) and \<5 BM Blasts (%); Investigators were to determine a response category for each patient by examination of bone marrow and blood counts at the time of hematologic recovery after induction or reinduction. Investigator assessment categories included CR, CRp, CRi (CR with morphologic CR with incomplete blood count recovery), PR (partial remission), treatment failure, and relapse.

Leukemia-free survival is censored at the last known alive date without report of relapse.

Overall survival is censored at the earlier of the cutoff date for analysis and the last date known to be alive for patients not known to have died.

Mortality of those patients enrolled in the study and receiving intervention

Sunesis Pharmaceuticals

Schedule A: vosaroxin injection (dose-escalation from 10 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (24-hour continuous IV \[CIV\] infusion of 400 mg/m2/day × 5 days)

Group 1 (Sch A, 10 to 90 mg/m2):

saroxin injection (dose-escalation from 70 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (2-hour intravenous \[IV\] infusion of 1 g/m2/day × 5 days)

Group 2 (Sch B, 70 to 90 mg/m2):

Group 3 (Sch A, First Relapse, 80 mg/m2)

Schedule B: vosaroxin injection (dose-escalation from 70 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (2-hour intravenous \[IV\] infusion of 1 g/m2/day × 5 days)

Group 4 (Sch B, First Relapse, 90 mg/m2):

Group 5 (Sch B, Primary Refractory, 90 mg/m2):

Group 1 (Sch A, 10 to 90 mg/m2)

Group 3 (Sch A, First Relapse, 80 mg/m2):

Group 4 (Sch B, First Relapse, 90 mg/m2)

Total

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Further study is needed to confirm the results due to limited sampling size. Statistical fields are not included here because no statistical testings were performed to compare any of the treatment groups. No p-values or odds ratios were reported.

Mike Johnston, Senior Director Regulatory Affairs

Vosaroxin injection 10 mg/m2 on Days 1 and 4 in combination with cytarabine (24-hour continuous IV \[CIV\] infusion of 400 mg/m2/day × 5 days)

Sch A, Cohort 10mg/m2

Vosaroxin injection 20 mg/m2 on Days 1 and 4 in combination with cytarabine (24-hour continuous IV \[CIV\] infusion of 400 mg/m2/day × 5 days)

Sch A, Cohort 20mg/m2

Vosaroxin injection 34 mg/m2 on Days 1 and 4 in combination with cytarabine (24-hour continuous IV \[CIV\] infusion of 400 mg/m2/day × 5 days)

SchA, Cohort 34mg/m2

Vosaroxin injection 50 mg/m2 on Days 1 and 4 in combination with cytarabine (24-hour continuous IV \[CIV\] infusion of 400 mg/m2/day × 5 days)

Sch A, Cohort 50mg/m2

Vosaroxin injection 70 mg/m2 on Days 1 and 4 in combination with cytarabine (24-hour continuous IV \[CIV\] infusion of 400 mg/m2/day × 5 days)

Sch A, Cohort 70mg/m2

Vosaroxin injection 80 mg/m2 on Days 1 and 4 in combination with cytarabine (24-hour continuous IV \[CIV\] infusion of 400 mg/m2/day × 5 days)

Sch A, Cohort 80mg/m2

Vosaroxin injection 90 mg/m2 on Days 1 and 4 in combination with cytarabine (24-hour continuous IV \[CIV\] infusion of 400 mg/m2/day × 5 days)

Sch A, Cohort 90mg/m2

Schedule B: vosaroxin injection 70 mg/m2 on Days 1 and 4 in combination with cytarabine (2-hour intravenous \[IV\] infusion of 1 g/m2/day × 5 days).

Sch B, Cohort 70 mg/m2

Sch B, Cohort 80mg/m2

Sch B, Cohort 90mg/m2

Patients experiencing a dose-limiting toxicity (DLT) during induction when treated with escalating doses of vosaroxin administered in combination with cytarabine on Days 1 and 4 in Schedule A, and with vosaroxin in escalating doses administered on Days 1 and 4 in Schedule B.

Incidence of Dose-Limiting Toxicity (DLT) to Determine Maximum Tolerated Dose in Schedule A and Schedule B of Dose Escalation Phase (Group 1 and Group 2)

All treated set which includes all enrolled patients who received any IMP.

Remission Rates (CR+CRp)

Leukemia-free Survival (LFS)

Overall Survival

30 Days

60 Days

Dose Escalation Phase Schedule A: vosaroxin injection (dose-escalation from 10 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (24-hour continuous IV \[CIV\] infusion of 400 mg/m2/day × 5 days)

Dose Escalation Phase Schedule B: vosaroxin injection (dose-escalation from 70 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (2-hour intravenous \[IV\] infusion of 1 g/m2/day × 5 days)

Expansion Phase: Schedule A: 80 mg/m2 vosaroxin on Days 1 and 4 in combination with cytarabine (24-hour CIV infusion at 400 mg/m2/day × 5 days)

Expansion Phase: Schedule B: 90 mg/m2 vosaroxin (dose-escalation) on Days 1 and 4 in combination with cytarabine (2 hour IV infusion at 1 g/m2/day × 5 days)

Expansion Phase Schedule B: 90 mg/m2 vosaroxin (dose-escalation) on Days 1 and 4 in combination with cytarabine (2 hour IV infusion at 1 g/m2/day × 5 days)

Group 5 (Sch B, Primary Refractory, 90 mg/m2)

All Cause Mortality

Overall Study

Immune System Diseases

Lymphoma

Hematologic Neoplasms

Leukemia, T-Cell

Leukemia, B-Cell

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Leukemia, Lymphoid

Lymphosarcoma

Patients will initially be consented for procurement of blood for generation of the transduced T-cells.

Three dose levels will be evaluated and a possible dose level -1 in case of unexpected toxicity at dose level 1. Each patient will receive one T cell infusion.

Each patient will receive one T cell infusion.

CD70.CAR Dose Levels / Cell Dose (transduced cells):

Dose Level -1: 3 x 10\^5 cells/kg Dose Level 1 (starting dose level): 1 x 10\^6 cells/kg Dose Level 2: 3 x 10\^6 cells/kg Dose Level 3: 1 x 10\^7 cells/kg

\*First three patients treated on the study will be adults 18 years of age or older.

Treatment Arm A

Bilal Omer, MD

This study is for patients that have lymph gland disease called Hodgkin or non-Hodgkin Lymphoma or T/NK-lymphoproliferative disease and the patients condition has come back or has not gone away after treatment, including the best treatment we know for these diseases.

Some patients with Lymphoma or T/NK-lymphoproliferative disease show signs of virus that is sometimes called Epstein Barr virus (EBV). This virus causes mononucleosis or glandular fever ("mono") before or at the time of their diagnosis. EBV is found in the cancer cells of up to half the patients with Hodgkin's and non-Hodgkin Lymphoma. This suggests that the EBV plays a role in causing Lymphoma. The cancer cells (in lymphoma) and some immune system cells infected by EBV are able to hide from the body's immune system and escape destruction.

T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including cells infected with viruses and tumor cells. T cells have been used to treat patients with cancers. T cells, that have been trained to kill EBV infected cells can survive in blood and affect the tumor. We have treated over 80 people on studies using T cells to target these diseases. About half of those patients who had disease at the time they got the cells had responses including some patients with complete responses (meaning the cancer could no longer be detected).

We think that if T cells are able to last longer in the body, they may have a better chance of killing EBV and EBV infected tumor cells. Therefore, in this study we will add a new gene to the EBV T cells that can cause the cells to live longer called C7R. We know that T cells need substances called cytokines (substances such as proteins released by specific cells of the immune system) to survive and that the cells may not get enough cytokines after the cells are infused into the body. We have added the gene C7R that gives the cells a constant supply of cytokine and helps them to survive for a longer period of time.

The purpose of this study is to find the largest safe dose of C7R-EBV T cells, and additionally to evaluate how long they can be detected in the blood and what affect they have on the cancer.

Patients will be enrolled to this study in two treatment groups: C7R-EBVSTs without lymphodepletion (Group A) and C7R-EBVSTs with lymphodepletion (Group B). The investigators will enroll patients into group B if limited expansion and clinical effectiveness is seen in Group A.

Patients will give blood to make C7R EBV T cells. These cells will be kept frozen until they are given to the patient.

The lines are made using a special process. To make the VSTs donor cells are mixed with small pieces of proteins, called peptides that are identical to proteins from EBV. First unwanted cells are separated from the donor blood. The unwanted cells have CD45RA on their surface and can be identified and removed from the product leaving behind only the T cells that contain a small number of VSTs. The cells are then stimulated with the peptides to make them grow. After about 9 days the growth of the VSTs starts to slow down and they are stimulated a second time (and possibly a third) with peptides together with cells from the donor that have been modified to help train the T cells to kill cells that are infected with EBV as well as a cell line (called ULCL) that helps the T-cells to grow. ULCL is made by infecting lymphocytes with EBV that has been made non-infectious by deleting a part of its DNA. ULCL is irradiated before use so that it cannot grow. Once enough VSTs are made they are frozen and tested to make sure they can recognize virus infected cells but not normal cells.

To get the C7R to be made by the T-cell, a gene is inserted into the T-cell. This is done using certain parts of a virus (known as a retrovirus). A retrovirus is a type of virus that inserts a copy of its own genetic material into the DNA of a different host cell. The retrovirus can carry the gene into the T cells. Patients that have received cells with a new gene in them will be followed for a total of 15 years in order to see if there are any long term side effects of gene transfer. Gene transfer is the insertion of genetic material into a cell.

Patients that enroll on this study will be assigned a dose of C7 R EBV T cells. The assigned dose of cells is based on body weight and height. In Group A, in this study patients will receive the C7 R EBV T cells. If in Group B, along with the C7R EBV T cells, patients will and may also receive cyclophosphamide and fludarabine. These two drugs are standard chemotherapy medicines and may be given before the T cells to make space in the blood for the T cells to grow after the patient has received them.

If in Group B, patients may receive cyclophosphamide and fludarabine, these drugs will be given intravenously (through an i.v. needle inserted in the vein or the central line) for 2 days and then fludarabine alone on the third day (Day -4, -3, -2) before the infusion. On Day 0, patients will be given an injection of C7 R EBV T cells into the vein through an IV line at the assigned dose.

Before receiving the T cell infusion, patients may be given a dose of Benadryl (diphenhydramine) and Tylenol (acetaminophen). The infusion will take between 1 and 10 minutes. Patients will be monitored in the clinic or hospital for about 2 hours. The treatment will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital or Houston Methodist Hospital. Patients should plan to stay in Houston for at least 2 weeks after the infusion to be monitored for side effects.

Patients will have follow-up visits with the clinic after the infusion (at scheduled visits weeks 2 and 6, and nursing follow up at weeks 1, 2, 4 and 6 after the infusion, and at months 3, 6, 9, and 12 after the infusion. The patients will also have nursing follow up annually for the next 15 years, and scheduled disease evaluations after the T-cell injection (at week 6 +/- 2 weeks after the infusion and then as clinically needed).

After disease re-evaluation, if the disease has not gotten worse, or if in the future it seems that patients might benefit and have not had a severe side effect caused by the infusion of the C7R EBV T cells, the patients may be eligible to receive one additional dose of the T cells. The dose will be at the same dose level as the first infusion and separated by at least 4 weeks to make sure there are no severe side effects between infusions. Patients that receive an additional dose of C7R EBV T-cells, should plan to stay in Houston for at least 2 weeks after the infusion to be monitored for side effects.

Medical tests before treatment--

Before being treated, patients receive a series of standard medical tests:

1. Physical exam
2. Blood tests to measure blood cells, kidney and liver function
3. Measurements of the tumor by routine imaging studies. Imaging studies that have been used in the past will be used to best assess the tumor (Computer Tomogram (CT) or Magnetic Resonance Imaging (MRI), and Positron Emission Tomography (PET/CT) and/or Bone Scan).

Medical tests during and after treatment--

Patients will receive standard medical tests while receiving the infusions and afterwards:

1. Physical exams
2. Blood tests to measure blood cells, kidney and liver function
3. Measurements of the tumor by routine imaging studies approximately 6 weeks after the infusion.
4. Tumor biopsy of an accessible tumor between 2-4 weeks after the infusion and as clinically indicated thereafter.

To learn more about the way the C7R EBV T cells are working and how long they last in the body, an extra amount of blood will be obtained on the day that chemotherapy starts, on the day of the T-cell infusion(s) and at the end of the T-cell infusion(s). Blood will also be obtained at 1, 2, 4, 6 weeks after the T-cell infusion(s) and every 3 months for the 1st year. Blood will then be obtained annually for the next 15 years and possibly at additional time points. The amount of blood taken will be based on weight with up to a maximum of 60 mL (12 teaspoons) of blood to be obtained at any one time. For children, the total amount of blood drawn will not be more than 3 mL (less than 1 teaspoon) per 2 lbs (1 kg) of body weight on any one day. This volume is considered safe, but may be decreased if the patient is anemic (have a low red blood cell count).

CHIMERIC ANTIGEN RECEPTOR TREATMENT TARGETING CD70 (SEVENTY)

1. Dose-limiting toxicity (CTCAE v5.0) is defined as any grade 3 or 4 non-hematologic toxicities (including allergic reactions and ICANS) that fails to return to Grade 2 within 72 hours or any grade 5 toxicity (additional assessment criteria may apply).

1. Response rate by International Working Group Criteria for AML and disease specific response criteria for patients with other hematological malignancies.

The response rate for AML is calculated as the overall complete response rate (CRMRD- + CR + CRi)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Safety Study of Human Cord Blood Derived, Culture Expanded Natural Killer Cell (PNK-007) Infusion With Subcutaneous Recombinant Human IL-2 (rhIL-2) in Adults With Relapsed and/or Refractory Acute Myeloid Leukemia (AML)	NCT02781467	Leukemia, Myelo...	PNK-007 Cyclophosphamid... Fludarabine Human recombina...	18 Years - 70 Years	Celularity Incorporated
A Safety Study of Human Cord Blood Derived, Culture Expanded Natural Killer Cell (PNK-007) Infusion With Subcutaneous Recombinant Human IL-2 (rhIL-2) in Adults With Relapsed and/or Refractory Acute Myeloid Leukemia (AML)	NCT02781467	Leukemia, Myelo...	PNK-007 Cyclophosphamid... Fludarabine Human recombina...	18 Years - 70 Years	Celularity Incorporated
Safety and Tolerability Study of Voreloxin and Cytarabine Combination in Acute Myeloid Leukemia in Humans	NCT00541866	Acute Myeloid L...	Voreloxin injec...	18 Years -	Sunesis Pharmaceuticals
CHIMERIC ANTIGEN RECEPTOR TREATMENT TARGETING CD70 (SEVENTY)	NCT06345027	Leukemia, Myelo... Leukemia, B-cel... Leukemia, T-Cel... Lymphoma	Treatment Arm A	- 75 Years	Baylor College of Medicine

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