Neoplasms

Blood and Lymph Conditions

All Conditions

Diseases and Abnormalities at or Before Birth

Symptoms and General Pathology

Rare Diseases

Leukemia

Congenital Abnormalities

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Hematologic Diseases

Chromosome Aberrations

Chromosome Disorders

Neoplasms by Histologic Type

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Cytarabine

Daunorubicin

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Dose escalation of selinexor with fixed doses of daunorubicin and cytarabine.

Induction Therapy may be followed by Consolidation Phase and Maintenance Phase as outlined in the Detailed Description and Intervention Descriptions.

Induction: Oral selinexor on days 1, 3, 8, 10, 15 and 17.

* Dose Level 2: 80 mg twice weekly.
* Dose Level 1 (starting dose): 60 mg twice weekly.
* Dose Level -1: 40 mg twice weekly.

Consolidation: Selinexor same dose as induction (days 1,3,8,10) unless dose limiting toxicity (DLT) dictates a dose reduction.

Maintenance: Selinexor at the same dose as induction on days 1 and 8 a 21 day cycle. They will continue for a maximum of 12 months.

Selinexor

Induction: Daunorubicin 60 mg/m\^2/day (days 1-3).

Consolidation: Daunorubicin 45 mg/m\^2/day (days 1-2).

Induction: Cytarabine 100 mg/m\^2/day (days 1-7).

Consolidation: Cytarabine 100 mg/m\^2/day (continuous infusion on days 1-5).

Kendra Sweet, M.D.

The main purpose of this study is to determine the safety of combining selinexor with daunorubicin and cytarabine. The maximal tolerated dose (MTD) of selinexor with daunorubicin and cytarabine will also be established.

Induction Therapy - Dose escalation of selinexor with Daunorubicin and cytarabine at fixed doses.

Consolidation Phase - Patients who are in complete remission (CR) or complete remission with incomplete count recovery (CRi) by day ≤70 and have recovered from any previous non- hematologic toxicity to baseline or grade ≤1 by day ≤70 following induction chemotherapy may go on to receive consolidation therapy for up to 2 cycles. The consolidation treatment phase will include up to two courses of therapy (28 day cycles) as follows:

Daunorubicin 45mg/m\^2/day (days 1-2) Cytarabine 100mg/m\^2/day (continuous infusion on days 1-5) Selinexor same dose as induction (days 1,3,8,10) unless dose limiting toxicity (DLT) dictates a dose reduction. Selinexor will be given 2 hours prior to daunorubicin on day 1.

A second cycle of consolidation therapy using the same doses as above will be administered, at the investigators discretion, between 28 and 42 days following initiation of the first consolidation treatment, after peripheral blood counts have recovered to CR, CRi levels, and after recovery from any non-hematologic toxicity to baseline or grade ≤1. Dose escalation of Selinexor will not occur during the consolidation phase.

Maintenance Phase - Patients who remain in CR, CRi after up to 2 cycles of consolidation and are not eligible for allogeneic stem cell transplant will be eligible for the maintenance phase of treatment after recovery from any previous non-hematologic toxicity to baseline or grade ≤1. Maintenance therapy will consist of:

Selinexor at the same dose as induction on days 1 and 8 of a 21 day cycle. They will continue for a maximum of 12 months.

Expansion Phase - Once the MTD has been established, there will be an expansion phase to enroll an additional 13 subjects at the MTD to better characterize the safety profile and tolerability.

A Study of Selinexor in Combination With Daunorubicin and Cytarabine for Untreated AML

A Phase 1 Investigator Sponsored Study of Selinexor in Combination With Daunorubicin and Cytarabine in Patients With Previously Untreated Poor-Risk Acute Myeloid Leukemia

MTD / Recommended Phase II Dose (RP2D) of selinexor with daunorubicin and cytarabine. Dose Limiting Toxicity (DLT): Non-hematologic - Any grade 3-4 drug-related non-hematologic toxicity, with the following exceptions: Nausea/vomiting or diarrhea adequately controlled with antiemetics/antidiarrheals; Infection or febrile neutropenia adequately controlled with antibiotics; Liver function abnormalities (without clinical symptoms) that recover to baseline or grade 0-1 within 7 days; Grade 3-4 electrolyte or metabolic laboratory abnormalities that are not considered clinically significant by the treating investigator/physician and that recover to baseline or grade 0-1 within 7 days; Alopecia. Hematologic - Grade 3-4 neutropenia and/or thrombocytopenia (thought to be due to marrow hypoplasia and NOT leukemic burden) that does not recover to grade ≤2 by day 56.

A CR designation requires that the patient achieve the morphologic leukemia-free state and have an absolute neutrophil count of more than 1,000/μL and platelets of 100,000/μL. A CRi designation requires that the patient achieve the morphologic leukemia-free state with incomplete recovery of neutrophils (\<1,000/μL) or platelets (\<100,000/μL).

Disease free survival is measured from the time measurement criteria are met for CR/CRi until the first date that relapse is objectively documented.

Time to progression is a secondary endpoint that will be measured as the time from when the patient started treatment to the time the patient is first recorded as having relapsed, or the date of death if the patient dies due to causes other than disease progression.

Overall survival is a secondary endpoint that will be measured as time from the start of treatment until death from any cause, or the last date the patient was known to be alive.

Karyopharm Therapeutics Inc

H. Lee Moffitt Cancer Center and Research Institute

Immune System Diseases

Infections

Respiratory Tract (Lung and Bronchial) Diseases

Nervous System Diseases

Skin and Connective Tissue Diseases

Preleukemia

Leukemia, Myelomonocytic, Juvenile

Myelodysplastic Syndromes

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Influenza, Human

Hematologic Neoplasms

Neoplasm, Residual

Neurofibromatoses

Neurofibromatosis 1

Neurofibroma

Monosomy

Lymphoma

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Nerve Sheath Neoplasms

Neoplasms, Nerve Tissue

Syndrome

Neoplastic Syndromes, Hereditary

Neurocutaneous Syndromes

Heredodegenerative Disorders, Nervous System

Neurodegenerative Diseases

Genetic Diseases, Inborn

Peripheral Nervous System Diseases

Neuromuscular Diseases

Neoplastic Processes

Bone Marrow Diseases

Myeloproliferative Disorders

Myelodysplastic-Myeloproliferative Diseases

Aneuploidy

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Neurofibromatosis

Neurofibromatosis Type 1

Lymphosarcoma

Chronic Myeloproliferative Disorders

Myelodysplastic/myeloproliferative Disease

Antirheumatic Agents

Anticonvulsants

Nootropic Agents

Fludarabine

Fludarabine phosphate

Rituximab

Melphalan

Levetiracetam

Busulfan

Antineoplastic Agents, Immunological

Antineoplastic Agents, Alkylating

Alkylating Agents

Patients will be treated on the most medically appropriate regimen with a preference for Flu/TBI Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.

Flu/Bu/Mel will the preference for patients with JMML or infants with leukemia.

Fludarabine 25mg/m2 IV on days -8 to -6 or days -4 to -2. 40mg/m2 IV on days -5 to -2.

Busulfan 82.1 mg\*hr/L IV on days -5 to -2 or days -8 to -5

200 mg/m2 intravenous given once on day-1

As seizures have occurred following high dose busulfan, all patients will be treated with Keppra beginning day -6 and continuing until day -1 per institutional guidelines.

Margaret MacMillan

This is a phase II, open-label, prospective study of T cell receptor alpha/beta depletion (α/β TCD) peripheral blood stem cell (PBSC) transplantation for children and adults with hematological malignancies

MT2021-08T Cell Receptor Alpha/Beta Depletion PBSC Transplantation for Heme Malignancies

Phase II, Open-Label, Prospective Study of T Cell Receptor Alpha/Beta Depletion (A/B TCD) Peripheral Blood Stem Cell (PBSC) Transplantation for Children and Adults With Hematological Malignancies

For the purposes of data and safety monitoring, this study is classified as high risk (investigator initiated under an IND). Therefore the following requirements will be fulfilled:

* The Masonic Cancer Center Data and Safety Monitoring Council (DSMC) will review the study's progress at least quarterly.
* The PI will comply with at least twice yearly monitoring of the project by the Masonic Cancer Center monitoring services.
* The PI will oversee the submission of all reportable adverse events per the definition of reportable in Section 11.5 to the Masonic Cancer Center's SAE Coordinator, the University of Minnesota IRB, and the FDA.

Monitor median rate of engraftment by 42 days.

Determine the rate of graft failure by day 100 (defined as lack of achievement of an ANC \>=500/mL with associated pancytopenia)

Determine the incidence of non-relapse mortality (NRM) at 100 days and 1 year

Number of participants experiencing progression free survival at one year follow up

Masonic Cancer Center, University of Minnesota

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Study of Selinexor in Combination With Daunorubicin and Cytarabine for Untreated AML	NCT02403310	Leukemia Acute Myeloid L... AML	Selinexor Daunorubicin Cytarabine	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
MT2021-08T Cell Receptor Alpha/Beta Depletion PBSC Transplantation for Heme Malignancies	NCT05735717	Hematologic Mal... Acute Leukemia Remission Acute Myeloid L... Acute Lymphobla... AML TP53 Intrachromosoma... Cytogenetic Abn... CNS Leukemia Minimal Residua... Myelodysplasia Juvenile Myelom... Somatic Mutatio... PTPN11 Gene Mut... N-RAS Gene Ampl... Neurofibromatos... NF1 Mutation CBL Gene Mutati... Monosomy 7 Chromosome Abno... Fetal Hemoglobi...	Fludarabine Busulfan Melphalan Rituximab Levetiracetam	- 60 Years	Masonic Cancer Center, University of Minnesota

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