Neoplasms

Blood and Lymph Conditions

All Conditions

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Philadelphia Chromosome

Leukemia, Myeloid, Chronic-Phase

Neoplasms by Histologic Type

Hematologic Diseases

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Translocation, Genetic

Chromosome Aberrations

Myeloid Leukemia

Chronic Graft Versus Host Disease

Chronic Myeloid Leukemia

Chronic Myeloproliferative Disorders

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Bosutinib

Nilotinib

Dasatinib

Tyrosine Kinase Inhibitors

Imatinib Mesylate

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Subjects who have been prescribed or administered bosutinib (Bosulif) for treatment of chronic-phase CML for less than 12 months.

Subjects who have been prescribed or administered dasatinib (Sprycel) for treatment of chronic-phase CML for less than 12 months.

Subjects who have been prescribed or administered imatinib (Gleevec) for treatment of chronic-phase CML for less than 12 months.

Subjects who have been prescribed or administered nilotinib (Tasigna) for treatment of chronic-phase CML for less than 12 months.

Subjects will be enrolled into this group if they are receiving bosutinib per standard of care. This is an observational study and no interventions will be made.

Subjects will be enrolled into this group if they are receiving dasatinib per standard of care. This is an observational study and no interventions will be made.

Subjects will be enrolled into this group if they are receiving imatinib per standard of care. This is an observational study and no interventions will be made.

Imatinib

Subjects will be enrolled into this group if they are receiving nilotinib per standard of care. This is an observational study and no interventions will be made.

Daniel Crona, PharmD, PhD

The purpose of this prospective, single-institution observational study is to evaluate associations between the pharmacokinetic (PK) parameters for tyrosine kinase inhibitors (TKIs) used to treat chronic phase chronic myeloid leukemia (CML) and clinical outcomes for up to 12 months. The study aims to identify associations between TKI clearance and/or exposure with demographic and clinical patient characteristics, CML milestones, medication toxicities, medication adherence, and germline genetic variants.

Because this is an observational study, standard-of-care therapy will not be altered during the course of participation. Blood samples will be collected at each study visit (up to 6 visits) over the course of 12 months to evaluate TKI concentrations, and PK parameters. Blood will also be collected during the first visit to isolate DNA for next generation sequencing (NGS). Demographic information will be collected at baseline, while clinical and medication adherence information will be collected at baseline and then throughout the study.

There will be no direct benefit to you for your participation. Risks are minor, but could include bruising, vein irritation, lightheadedness/dizziness, and/or infection from blood draws, as well as potential loss of confidentiality.

This study is a prospective, single-institution observational study designed to evaluate associations between the pharmacokinetic (PK) parameters (e.g., clearance and exposure) for four tyrosine kinase inhibitors (TKIs) used to treat chronic phase CML with key clinical milestones in CML, as well as associations between TKI PK and medication-induced toxicities and medication adherence. The four TKIs to be evaluated in this study include bosutinib, dasatinib, imatinib, or nilotinib, while the key clinical milestones for CML include complete hematologic response (CHR) at one month, early molecular response (EMR) at 3 months and 6 months, and major molecular response (MMR) at 9 months and 12 months. A total of 150 subjects will be enrolled in the study. The enrolled study subjects will have been prescribed one of these four TKIs by a UNC medical oncologist or advanced practice provider for their diagnosed chronic phase CML. Research personnel will identify potential research subjects using data from the Carolina Data Warehouse, and pharmacy prescription claims data. Research personnel will contact patients regarding study participation in-person in clinic or over the telephone to receive informed consent.

For patients who are newly initiated on a TKI, assessment procedures will occur as close to monthly time points as possible (baseline, 1,3,6,9 12, 15, etc) with at least 30 days between draws for time points at and after 3 months. For the blood collection at 1 month, there will be a +/- 2 week window. Each patient will be enrolled in the study for a maximum of 6 different study visit days, for a total of 12 total months. If a participant changes treatment to a new TKI of interest, the participant may be followed for an additional 12 months. Active participation in the study is expected to last approximately one year for these subjects. Subjects may also be identified and enrolled after having already been initiated on TKI therapy, in which case, the duration since initiation of their TKI will be 12 total months and they will enter at the closes study time point. If enrolled subjects require a change of therapy, they will restart their participation under the new TKI at baseline and be followed for an additional 12 months. Subjects who complete the 12-month study duration and subsequently change therapy may continue participation under the new TKI and restart their participation at baseline.

All study visits will align with standard-of-care follow-up appointments such that no additional research only visits to the UNCMC are required of the subjects. Up to seventy-two hours prior to each visit, one member of the study personnel will telephone (or email, if unreachable by telephone) the subject to remind them to take their medication the days prior to their study visit, but not the day of their study visit prior to blood sample collections. Subjects will also be reminded to record the exact time and date of the two doses prior to their study visit date. Subjects may resume their normal TKI dosing regimen after completion of the study visit, at the discretion of the treating provider.

At each clinic visit, the subject will have two blood samples drawn, and will be required to complete a series of surveys (Appendices D, E). Each blood sampling will collect approximately 4mL of peripheral blood, for a total of approximately 8mL of blood per study visit. Each subject will also have an additional 4mL of blood collected once at their first study visit for DNA extraction. The first research blood sample will be collected at the beginning of the clinic visit alongside the routine blood draws and processed according to the procedures listed in Appendix C. Surveys will then be administered during the visit, and lab results and clinical data will be collected. Prior to discharge, a final research blood sample will be drawn. Phlebotomy will be performed by trained phlebotomists, nurses, or physicians in the UNCMC. Blood samples will be processed per protocol by the study personnel as trained by PI or co-investigators. A detailed summary of clinic visit procedures can be found in Appendices A and B.

For subjects enrolled on the same day as their first study visit, blood samples will be drawn at the end of the study visit. All subsequent study visits will take place as described above.

For all study subjects, two blood samples will be taken at each study visit. These samples will be used to quantify TKI concentrations in the plasma. Later, the TKI concentration/time information will be used in PK analyses that will estimate clearance and exposure. Additionally, during the subject's first study, an additional blood sample will be obtained to isolate DNA for NGS. Throughout the study, all blood samples will be collected by a phlebotomist or nurse.

Precision Dosing of Tyrosine Kinase Inhibitors in CML Patients

Preliminary Evaluation of TKI Exposure-response Relationships in Real World Patients (RWPs) With Chronic Myelogenous Leukemia (CML)

TKI exposure/clearance will be evaluated by measuring levels of TKI in the blood during the 12 month study period. BCR-ABL transcripts at 12 months will be compared against the TKI levels.

CHR at 1 month, defined as complete normalization of peripheral blood counts with leukocyte count \< 10 x 1E9/L, platelet count \< 450 x 1E9/L, no immature cells (such as myelocytes, promyelocytes, no blasts in peripheral blood, and no signs and symptoms of disease with disappearance of palpable splenomegaly.

Incidence of EMR at 3 and 6 months, defined as BCR-ABL transcript ≤ 10%, will be evaluated, and will be compared against TKI levels at 3 and 6 months.

Incidence of MMR at 9 and 12 months, defined as BCR-ABL transcript ≤ 0.1%, will be evaluated, and will be compared against TKI levels at 9 and 12 months.

BCR-ABL transcripts will be obtained at each time point. The Log10 change in BCR-ABL transcripts will be evaluated, and will be compared against TKI levels at each time point.

Subject adherence will be evaluated at each time point during standard-of-care study visits. The Wilson's 3-item Adherence Score (WAS) tool will be administered to each subject at each visit in survey form. The WAS tool provides a score from 0-100 (0, worst; 100, best) to evaluate adherence to medications in the last 30 days.

Associate TKI exposure/clearance with subject-reported toxicity assessments. Medication-induced toxicity assessments will be conducted at each study visit using the validated MD Anderson Symptom Inventory for CML (MDASI-CML) tool. The MDASI-CML tool asks subjects to rate symptom severity in the last 24 hours on a 0-10 scale (0, not present; 10, as bad as one can imagine). The MDASI-CML also evaluates symptom interference with daily activities in the same manner.

UNC Lineberger Comprehensive Cancer Center

KDS-1001 is infused on Day 1 of each 14 day cycle. Patients will receive 6 cycles of KDS-1001 treatment.

Cycles 1-6 (14 days per cycle)

1 x 109/KDS-1001 cells/infusion administered on day 1 of each cycle

KDS-1001

Caitlyn Campbell

Lynn Volk

Lindsay Rein, MD

This open label, non-randomized, prospective phase I study is designed to evaluate if the addition of natural killer cell therapy (KDS-1001) to tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia (CML) patients with persistent or recurrent molecular residual disease (MRD) after at least one year of TKI therapy will allow patients to achieve RT-PCR negativity (MRD negative). This may have implications for future TKI cessation studies.

IIT PH1 KDS-1001 in Patients With CML

A Phase I Trial of Incorporating Natural Killer (K-NK) Cells for Patients With Chronic Myeloid Leukemia (CML) and Molecular Residual Disease After Tyrosine Kinase Inhibitor (TKI) Therapy

At least one (1) log reduction in IS OR negative to at least MR4.5 via PCR-based testing

Number of adverse events as measured by self report

Kiadis Pharma

Assistant Professor of Medicine, Hematologic Malignancies & Cell Therapy

Immune System Diseases

Syndrome

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Hematologic Neoplasms

Leukemia, Lymphocytic, Chronic, B-Cell

Preleukemia

Myelodysplastic Syndromes

Lymphoma

Precancerous Conditions

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Leukemia, B-Cell

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Lymphocytic Leukemia

Acute Graft Versus Host Disease

Lymphosarcoma

Myeloablative conditioning (Flu/Cy/TBI) followed by CD3/19/34 selected stem cell graft.

Stem Cell Transplantation

Minocher M Battiwalla, M.D.

Background:

- People who have some kinds of cancer can benefit from donated bone marrow stem cells. These stem cells help produce healthy bone marrow and slow or stop the spread of abnormal cells. However, stem cells transplants do not always work. Also, they may have serious side effects that can cause illness or death. The Bone Marrow Stem Cell Transplant Program is studying methods to make stem cell transplant procedures safer and more effective.

Objectives:

- To test a new procedure that may improve the success and decrease the side effects of stem cell transplants.

Eligibility:

* Individuals 10 to 75 years of age who have a life-threatening illness that may require a stem cell transplant.
* Healthy siblings who are able to provide stem cells for transplant.

Design:

* Participants will be screened with a medical history, physical exam, and blood and urine tests.
* Donor procedures:
* Stem cell donors will start by having apheresis to donate white blood cells.
* Donors will receive filgrastim shots for 5 days to help move stem cells into the blood for collection.
* Donors will have another round of apheresis to donate the stem cells for transplant.
* Recipient procedures:
* Before the transplant, recipients will have radiation twice a day for 3 days and chemotherapy for 7 days.
* After the radiation and chemotherapy, recipients will receive the stem cells provided by the donor.
* After the transplant, recipients will receive the white blood cells provided by the donor.
* Recipients will be monitored closely for 4 months to study the success of the transplant. They will have more followup visits at least yearly thereafter.
* Recipients will have a research apheresis prior to transplant and at 3 months.

Peripheral blood stem cell transplant research carried out by the NHLBI BMT Unit focus on transplant techniques designed to decrease graft versus host disease (GVHD), increase the graft-versus-leukemia (GVL) effect and reduce the risk of post-transplant graft rejection.

Through incremental transplant clinical trials we have shown that by controlling the stem cell (CD34+ cell) and T lymphocyte (CD3+ cell) dose, severe GVHD can be reduced whilst beneficial GVL effects can be preserved. We found that T cell depleted transplants using the Nexell/Baxter Isolex 300i system and subsequently, the Miltenyi CD34+ CliniMACs system to obtain high CD34+ doses depleted of lymphocytes were safe to administer and associated with less severe acute GVHD and promising response rates and overall survival. Our previous trials have helped us to create the transplant environment (significant lymphodepletion and minimal post transplant immunosuppression) that make for an ideal platform for adoptive cellular immunotherapy

This protocol is designed to evaluate the safety and efficacy of an improved ex vivo graft manipulation procedure using the Miltenyi CliniMACs CD 34, 3 and 19 selection system in HLA-matched sibling allogeneic peripheral blood stem cell transplant. The manipulation of the graft is the primary research intervention and all other aspects of clinical management on this protocol are the standard of care. The target CD34+ dose range will be 3 times 10(6)/kg to 10 times 10(6)/kg and the target CD3+ dose range will be 5 x 10(4)/kg to 1 times 10(6)/kg. The technique will preserve greater numbers of NK cells. Once we demonstrate adequacy of engraftment in the first ten recipients, we plan an amendment to permit further use of this protocol to serve as a platform for several planned adoptive cellular therapy initiatives.

The protocol will accrue up to 44 subjects aged 10-75 with a hematological malignancy and their HLA-matched sibling donors, in whom allogeneic stem cell transplantation from an HLA-matched sibling would be routinely indicated. Diagnostic categories will include acute and chronic leukemia, myelodysplastic syndromes, lymphomas, multiple myeloma and myeloproliferative syndromes.

Subjects will receive a myeloablative conditioning regimen of cyclophosphamide (120 mg/kg total), fludarabine (125 mg/m(2) total) and total body irradiation (1200 cGy with lung shielding to 600 cGy), followed by an infusion of a stem cell product prepared using the Miltenyi CliniMACS system for CD34, 3 \& 19 selection. Older subjects will receive a lower dose of irradiation (600 cGy) without lung shielding to reduce the regimen intensity.

The overall objective is to assess the feasibility of using this system as a platform for cellular immunotherapy initiatives. The primary study endpoint will be overall survival at day plus 200. Non-relapse mortality at day plus 200 will be monitored for safety. Secondary endpoints will be standard transplant outcome variables such as non-hematologic toxicity, incidence and severity of acute and chronic GVHD and relapse of disease.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Precision Dosing of Tyrosine Kinase Inhibitors in CML Patients	NCT03885830	CML, Chronic Ph... CML (Chronic My... CML - Philadelp... Chronic Myeloid... Chronic Myeloid...	Bosutinib Dasatinib Imatinib Nilotinib	18 Years -	UNC Lineberger Comprehensive Cancer Center
IIT PH1 KDS-1001 in Patients With CML	NCT04808115	CML (Chronic My...	KDS-1001	-	Duke University
Improving Blood Stem Cell Collection and Transplant Procedures	NCT01517035	Myelodysplastic... Chronic Myeloge... Acute Lymphobla... CML (Chronic My... CLL (Chronic Ly...	Stem Cell Trans...	2 Years - 80 Years	National Institutes of Health Clinical Center (CC)
Improving Blood Stem Cell Collection and Transplant Procedures	NCT01517035	Myelodysplastic... Chronic Myeloge... Acute Lymphobla... CML (Chronic My... CLL (Chronic Ly...	Stem Cell Trans...	2 Years - 80 Years	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for cml (chronic myelogenous leukemia