Clinical Research Directory

Pembrolizumab and Decitabine With or Without Venetoclax in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome That Is Newly-Diagnosed, Recurrent, or Refractory

This phase Ib trial studies the side effects and best dose of pembrolizumab and how well it works in combination with decitabine with or without venetoclax in treating patients with acute myeloid leukemia or myelodysplastic syndrome that is newly-diagnosed, has come back (recurrent), or does not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. This trial may help doctors find the best dose of pembrolizumab that can be safely given in combination with decitabine with or without venetoclax, and to determine what side effects are seen with this treatment.

HM2023-05: GTB-3650 Trike for High Risk MDS and R/R AML

This is a Phase I dose finding study of GTB-3650 (anti-CD16/IL-15/anti-CD33) Tri-Specific Killer Engager (TriKE®) for the treatment of select CD33-expressing refractory/relapsed myeloid malignancies in adults ≥ 18 years of age who are not a candidate for potentially curative therapy, including hematopoietic stem cell transplantation, and are refractory to, intolerant of, or ineligible for therapy options that are known to provide clinical benefit. The hypothesis is GTB-3650 TriKE will induce natural killer (NK) cell function by targeting malignant cells, as well as, CD33+ myeloid derived suppressor cells (MDSC) which contribute to a tumor induced immunosuppression. Because CD16 is the most potent activating receptor on NK cells, this single agent may induce a targeted antiCD33+ tumor response

Bleximenib in Combination With Standard Induction and Consolidation Therapy Followed by Maintenance for Treatment of Patients With Acute Myeloid Leukemia (AML)

The current standard of care treatment for adult patients with acute myeloid leukemia (AML) consists of chemotherapy and, if indicated, donor stem cell transplantation. Bleximenib blocks the interaction between a protein called menin and another protein called KMT2A in the leukemia cells. When this interaction is disrupted in AML with mutations in the NPM1 or KMT2A gene, bleximenib can cause leukemia cells to die. The main objective is to assess if treatment with bleximenib, when added to chemotherapy treatment will improve treatment outcome in adult participants with newly diagnosed AML who present with mutations in the NPM1 or KMT2A genes. This is a randomized, double-blind, placebo-controlled, phase 3 clinical trial. All of the participants will receive standard chemotherapy treatment, combined with either bleximenib or a placebo. A placebo is a substance that looks like the study medicine but has no active ingredients (e.g., a sugar pill). In a double blind trial neither the participant nor the doctor know if placebo or active study drug is given. After the end of the protocol treatment there will be an observational follow-up of 4 years from the time of inclusion of the last patient. The results of the different treatment groups will be compared. 875 previously untreated patients with AML with a specific change in the DNA of the leukemia cells (a KMT2A rearrangement or a NPM1 mutation) will be included. Participants must be 18 years or older and considered eligible for intensive chemotherapy.

Pemigatinib After Chemotherapy for the Treatment of Newly Diagnosed Acute Myeloid Leukemia

This phase I trial identifies the best dose and clinical benefit of giving pemigatinib following standard induction chemotherapy in patients with newly diagnosed acute myeloid leukemia. Pemigatinib selectively inhibits FGFR (fibroblast growth factor receptor) activity, a receptor that may contribute to the growth of leukemia cells. The genetic changes responsible for activating the growth of leukemia cells can be unique to each patient and can change during the course of the disease. Chemotherapy drugs, such as cytarabine and daunorubicin work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

MYELOMATCH: A Screening Study to Assign People With Myeloid Cancer to a Treatment Study or Standard of Care Treatment Within myeloMATCH (MyeloMATCH Screening Trial)

This MyeloMATCH Master Screening and Reassessment Protocol (MSRP) evaluates the use of a screening tool and specific laboratory tests to help improve participants' ability to register to clinical trials throughout the course of their myeloid cancer (acute myeloid leukemia or myelodysplastic syndrome) treatment. This study involves testing patients' bone marrow and blood for certain biomarkers. A biomarker (sometimes called a marker) is any molecule in the body that can be measured. Doctors look at markers to learn what is happening in the body. Knowing about certain markers can give doctors more information about what is driving the cancer and how to treat it. Testing patients' bone marrow and blood will show doctors if patients have markers that specific drugs can target. The marker testing in this study will let doctors know if they can match patients with a treatment study (myeloMATCH clinical trial) that tests treatment for the type of cancer they have or continue standard of care treatment with their doctor on the Tier Advancement Pathway (TAP).

Induction and Consolidation With Fludarabine, Cytarabine, Idarubicin, and Venetoclax for the Treatment of Acute Myeloid Leukemia

This phase II trial compares induction and consolidation therapy with fludarabine, cytarabine, idarubicin, and venetoclax to cytarabine and daunorubicin induction and cytarabine consolidation for the treatment of acute myeloid leukemia (AML). Patients with AML often receive induction and consolidation therapy. Induction therapy is given first to get the patient's AML under control (remission). Consolidation therapy is given after the cancer has disappeared following the initial therapy. Consolidation therapy is used to kill any cancer cells that may be left in the body. Chemotherapy drugs, such as fludarabine, cytarabine, idarubicin, and daunorubicin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving fludarabine, cytarabine, idarubicin, and venetoclax for induction and consolidation therapy may be more effective in treating AML.

Prophylactic and Therapeutic DLI-X for Leukemia Relapse After HCT

The primary objective of this proposal is to conduct the first-in-human randomized clinical trial evaluating prophylactic DLI-X (pro-DLI-X) for relapse prevention following matched sibling donor (MSD) or haploidentical (haplo) hematopoietic cell transplantation (HCT) in patients with hematologic malignancies. Additionally, the study aims to assess the safety and efficacy of therapeutic DLI-X (t-DLI-X) compared to t-DLI alone in patients with minimal residual disease (MRD+) or overt relapse post-alloHCT. For patients with CD19-positive lymphoid malignancies, the study will incorporate blinatumomab, while those with myeloid or CD19-negative lymphoid malignancies will receive t-DLI-X or t-DLI alone. We hypothesize that both pro-DLI-X and t-DLI-X, with or without blinatumomab, will demonstrate safety and superior efficacy by enhancing graft-versus-leukemia (GvL) effects mediated by natural killer (NK) cells, γδ T cells, and CD8+ T cells, while maintaining manageable and treatment-responsive graft-versus-host disease (GvHD).

A Study of BGB-11417 in Participants With Myeloid Malignancies

The study will determine the safety, tolerability, recommended Phase 2 dose (RP2D) and preliminary efficacy of BGB-11417 as monotherapy and in combination with azacitidine in participants with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)or MDS/myeloproliferative neoplasm (MPN) .

Xylitol Dental Wipes for the Reduction of Bloodstream Infection Risk in Children With Acute Myeloid Leukemia

This phase III trial compares the effect of xylitol dental wipes to dental wipes without xylitol for the reduction of bloodstream infection in children with acute myeloid leukemia (AML). Xylitol is a naturally occurring sugar compound found in fruits and vegetables. Xylitol has been shown to limit the growth of bacteria in the mouth, and to reduce cavities, plaque on the teeth, and inflammation of the gums. Treatment for AML includes chemotherapy. Patients receiving chemotherapy for AML have a risk of developing bloodstream infections. Bloodstream infections can make patients very sick, can contribute to delays in treatment, and can even cause death. In AML patients, bacteria or fungus (yeast) can sometimes enter the bloodstream from the mouth. Using xylitol dental wipes may help to reduce bloodstream infections in children being treated for AML.

A Study to Assess Adverse Events and How Intravenous (IV) Pivekimab Sunirine Moves Through the Body in Pediatric Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML)

Acute myeloid leukemia (AML) is an aggressive blood cancer, withwith few options for participants who relapse after treatment or who don't respond to treatment. This study will assess the adverse events and how pivekimab sunirine moves through the body in pediatric participants with relapsed or refractory (R/R) AML. Pivekimab sunirine is a drug being evaluated in the treatment of AML. This is an open label, single arm study, participants will be enrolled in 1 of the 3 cohorts based on their age and will receive pivekimab sunirine at a dose based on their weight. Around 18 pediatric participants with a diagnosis of AML will be enrolled in the study at approximately 30 sites around the world. Participants will receive intravenous (IV) pivekimab sunirine alone. The total study duration is approximately 28 months. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, and checking for side effects.

Venetoclax and HMA Treatment of Older and Unfit Adults With FLT3 Mutated Acute Myeloid Leukemia (AML) (A MyeloMATCH Treatment Trial)

This phase II MyeloMATCH treatment trial compares the usual treatment of azacitidine and venetoclax to the combination treatment of azacitidine, venetoclax and gilteritinib in treating older and unfit patients with acute myeloid leukemia and FLT3 mutations. Azacitidine is a drug that is absorbed into DNA and leads to the activation of cancer suppressor genes, which are genes that help control cell growth. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Gilteritinib is in a class of medications called kinase inhibitors. It works by blocking the action of a certain naturally occurring substance that may be needed to help cancer cells multiply. This study may help doctors find out if these different approaches are better than the usual approaches. To decide if they are better, the study doctors are looking to see if the study drugs lead to a higher percentage of patients achieving a deeper remission compared to the usual approach.

Tagraxofusp and Azacitidine With Venetoclax in Newly Diagnosed Secondary AML After Hypomethylating Agents

A treatment cycle is 28 days. Tagraxofusp will be administered at 9 mcg/kg IV over 15 minutes (-5 or +15 minutes) daily for 3 consecutive days (or 3 doses over a period not to exceed 10 days if postponement is required to allow for toxicity resolution), followed by azacitidine administered at 75 mg/m2 SQ or IV daily on Day 4 through Day 10. Venetoclax will begin on Day 4 and continue through Day 24 (21 consecutive days). A bone marrow biopsy (BM Bx) will be performed on Day 24 (+3 days) of Cycle 1. Subjects who do not achieve a CRm will proceed with the next cycle of Induction Phase study treatment, irrespective of hematologic laboratory values. Cycle 2+ will consist of tagraxofusp 9 mcg/kg IV over 15 minutes daily for 3 consecutive days (Day 1-3 or 3 doses over a period not to exceed 10 days if postponement is required to allow for toxicity resolution), azacitidine 75 mg/m2 SQ or IV on Day 1 through Day 7 or Days 1-7 or 1-5, 8-9 and venetoclax 400 mg daily Day 1 through Day 21. A bone marrow biopsy (BM Bx) will be performed on Day 21 (+3 days) of Cycle 2. If a CRm is obtained or maintained, the subject will move to or remain on the Continuation Phase. Subjects who do not achieve a marrow CR (CRm) after Cycle 2 will proceed with the next cycle of Induction Phase study treatment as described above, irrespective of hematologic laboratory values. If a CRm is obtained after Cycle 3 or 4, the subject will move to the Continuation Phase . If a CRm is not obtained after Cycle 4, study treatment will be discontinued and the subject will move to follow up. If per the investigator, the subject is receiving clinical benefit, study treatment may continue until toxicity or completion of 12 total cycles. A BM Bx will be performed at least every 3 cycles for these subjects.

A Study of Azacitidine and Venetoclax Versus a Stem Cell Transplant in People 65 Years and Older With Acute Myeloid Leukemia

The researchers are doing this study to find out if an allogeneic hematopoietic stem cell transplant (HSCT) or maintenance therapy with azacitidine and venetoclax is more effective at keeping AML from coming back (relapsing).

Bortezomib, Sorafenib Tosylate, and Decitabine in Treating Patients With Acute Myeloid Leukemia

This phase I trial studies the side effects and the best dose of bortezomib and sorafenib tosylate when given together with decitabine in treating patients with acute myeloid leukemia. Bortezomib and sorafenib tosylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving bortezomib and sorafenib tosylate together with decitabine may work better in treating acute myeloid leukemia.

Use of Electrical Bioimpedance in Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) Patients (Bioimpedance)

The goal of this project is to test non-invasive, painless skin electrical bioimpedance (BioZ) measurements as an adjunctive biomarker to standard bone marrow biopsies.

Safety and Efficacy of Ponatinib for Treatment of Pediatric Recurrent or Refractory Leukemias, Lymphomas or Solid Tumors

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and efficacy of ponatinib in children aged 1 to \< 18 years with advanced leukemias, lymphomas, and solid tumors.

A Vaccine (CMV-MVA Triplex Vaccine) for the Enhancement of CMV-Specific Immunity and the Prevention of CMV Viremia in Patients Undergoing Haploidentical Hematopoietic Stem Cell Transplant

This phase Ib trial tests the safety, side effects, and how well cytomegalovirus (CMV)-modified vaccinia Ankara (MVA) Triplex vaccine works in enhancing CMV-specific immunity and preventing CMV viremia in patients undergoing haploidentical hematopoietic stem cell transplant. Haploidentical stem cell transplantation (haploHCT) has advanced to become the predominant procedure for patients lacking a matched donor. Compared to matched related donor transplants, the rate of significant CMV infection is higher in patients undergoing a haploHCT. Significant CMV infection is associated with an increased risk of complications and death. Vaccination is the main preventative approach to limit complications and death in immunocompromised patients at high risk of post-stem cell transplant infections. CMV-MVA Triplex vaccine, is a CMV vaccine based on the attenuated poxvirus, modified vaccinia Ankara (MVA), developed to enhance CMV-specific immunity in both healthy stem cell transplant donors and stem cell transplant patients to prevent significant CMV infection post-stem cell transplant. Giving CMV-MVA triplex vaccine may be safe, tolerable and/or effective in enhancing cytomegalovirus (CMV)-specific immunity and preventing CMV viremia in patients undergoing a haploHCT.

Randomization for the Identification of Best Treatment Intensity for Less Fit Adults With Acute Myeloid Leukemia and Myeloid Neoplasms

This clinical trial studies whether less fit adults with acute myeloid leukemia (AML) or myeloid neoplasms are willing to let a computer program decide (randomization) whether they receive lower- or higher-intensity chemotherapy. Historically, treatment decision-making for patients with AML or myeloid neoplasms has divided patients into two categories, with patients considered fit receiving intensive "curative" chemotherapy, and patients considered unfit, such as older patients with a higher risk of early death from therapy, receiving non-intensive "palliative" therapy or no therapy. With the introduction of new treatment agents, it has become difficult to determine the difference between intensive and non-intensive therapy, especially for patients considered unfit for whom treatment-related side effects remain a concern. Treatment intensity is best identified through randomized trials but often patients are unwilling to undergo randomization due to preset beliefs. However, with improved supportive care and the awareness that new treatment agents may have similar risks as intensive therapy, it may be possible that more patients are willing to be randomized. This may help identify the best treatment intensity for less fit adults with AML or myeloid neoplasms, which may improve outcomes.

CD45RA Depleted Peripheral Stem Cell Addback for Viral or Fungal Infections Post TCRαβ/CD19 Depleted HSCT

The major morbidities of allogeneic hematopoietic stem cell transplant with non-human leukocyte antigen (HLA) matched siblings are graft vs host disease (GVHD) and life threatening infections. T depletion of the donor hematopoietic stem cell graft is effective in preventing GVHD, but immune reconstitution is slow, increasing the risk of infections. An addback of donor CD45RA (naive T cells) depleted cells may improve immune reconstitution and help decrease the risk of infections.

First-in-human (FIH) Trial of GEN3018 in Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML) or Higher-risk Myelodysplastic Syndrome (HR-MDS)

The drug that will be investigated in the trial is an antibody, GEN3018. Since this is the first trial of GEN3018 in humans, the main purpose is to evaluate safety. In addition to safety, the trial will determine the recommended GEN3018 dose(s) to be tested in a larger group of participants and assess preliminary anti-tumor activity of GEN3018. GEN3018 will be studied in refractory (resistant to treatment) or relapsed (disease has returned) acute myeloid leukemia (also known as R/R AML) and refractory or relapsed higher-risk myelodysplastic syndrome (also known as R/R HR-MDS). The trial consists of 2 parts: 1. Part 1 Dose Escalation will test increasing doses of GEN3018 to identify a safe dose level to be tested in the next part 2. Part 2 Dose Refinement will further test the GEN3018 dose(s) determined from the Dose Escalation. Up to 78 participants may be treated in this trial (up to 60 participants in Part 1; up to 18 participants in Part 2). For an individual participant in the trial, the estimated treatment duration will be up to 1 year. Participation in the trial will require regular scheduled visits to the site. At site visits, there will be various tests (such as blood draws) to monitor whether the treatment is safe and effective. Participants will also be contacted every 3 months after treatment ends to monitor how they are doing. All participants in the trial will receive active drug (ie, GEN3018); no one will be given placebo.

Motixafortide for MRD Sensitization in AML

This is a pilot phase I study evaluating the effect of motixafortide on determination of measurable residual disease (MRD) level in patients with acute myeloid leukemia (AML) who have completed induction treatment. Consenting and eligible patients will undergo standard of care (SOC) bone marrow and peripheral blood assessments with SOC MRD assays, followed by a single injection of motixafortide. Ten to 14 hours after injection, the patient will undergo peripheral blood collection for the same applicable MRD tests

Phase III Study of Induction and Consolidation Chemotherapy With Venetoclax in Patients With Newly Diagnosed AML or MDS-EB-2

A Randomized, Placebo-Controlled Phase III Study of Induction and Consolidation Chemotherapy With Venetoclax in Adult Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome With Excess Blasts-2

Study of Individuals and Families With Aberrations in DDX41 or Similar Cancer Predisposition Variants

Background: Hereditary hematopoietic malignancy (HHM) syndromes are a group of inherited disorders that raises the risk of blood cancers. Many people with HHMs have changes in a gene (DDX41) that makes it more likely that they will develop myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), or other cancers. This natural history study will explore the link between HHM syndromes and these diseases. Objective: To study the link between HHM and MDS/AML. Eligibility: People aged 1 month and older with HHM. Relatives with HHM are also needed. Design: Participants aged 3 years and older will have 1 initial clinic visit with the option to follow-up annually. They will undergo these procedures: They will have a physical exam with blood and urine tests. They may give samples of saliva, stool, nails, and skin. Their ability to do normal activities will be reviewed. Some may have a bone marrow biopsy: A tissue sample will be drawn from inside a bone. They may answer questions about their health and family medical history. Participants younger than 3 years, and those who cannot come to the clinic, will be contacted by phone or email. Their samples may be collected locally and sent to researchers. For participants who have changes in their DDX41 gene: Researchers will contact them or their primary care provider once a year for 10 years. Researchers will check on participants health and collect any new test results. Some may be asked to send new samples. Participants who do not have changes in their DDX41 gene may be contacted yearly, or less often, for 10 years. Some participants may be asked to return to the clinic if needed.

90Y-DOTA-anti-CD25 Basiliximab, Fludarabine, Melphalan, and Total Marrow and Lymphoid Irradiation for the Treatment of High-Risk Acute Leukemia or Myelodysplastic Syndrome

This phase I trial is to find out the best dose, possible benefits and/or side effects of 90Y-DOTA-anti-CD25 basiliximab given together with fludarabine, melphalan, and total marrow and lymphoid irradiation (TMLI) in treating patients with high-risk acute leukemia or myelodysplastic syndrome. 90Y-DOTA-anti-CD25 basiliximab is a monoclonal antibody, called basiliximab, linked to a radioactive agent called 90Y-DOTA. Basiliximab attaches to CD25 positive cancer cells in a targeted way and delivers 90Y-DOTA to kill them. Fludarabine and melphalan are common chemotherapy drugs used to prepare the bone marrow to receive transplanted cells. TMLI is a different type of targeted radiation therapy used to prepare the bone marrow to receive transplanted cells. Giving 90Y-DOTA-anti-CD25 basiliximab together with fludarabine, melphalan, and TMLI may help prepare the bone marrow to receive the transplanted cells for improved transplant outcomes in patients with acute leukemia or myelodysplastic syndrome.