SUSPENDED

Natural Killer (NK) Cells in Combination With Interleukin-2 (IL-2) and Transforming Growth Factor Beta (TGFbeta) Receptor I Inhibitor Vactosertib in Cancer

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Conditions

Colorectal CancerHematologic MalignancyRectum CancerAcute Myeloid LeukemiaMyelodysplastic SyndromesAcute Lymphoblastic LeukemiaChronic Myeloid LeukemiaChronic Lymphocytic LeukemiaHodgkin LymphomaNon Hodgkin LymphomaMyeloproliferative SyndromePlasma Cell MyelomaGastric CancerEsophageal CancerEsophagus CancerGastric Cancer, MetastaticUnresectable Esophageal CancerMetastatic Esophageal Cancer

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

One of the ways that cancer grows and spreads is by avoiding the immune system.NK cells are immune cells that kill cancer cells, but are often malfunctioning in people with colorectal cancer and blood cancers. A safe way to give people with colorectal cancer and blood cancers fresh NK cells from a healthy donor has recently been discovered. The purpose of this study is to show that using two medicines (vactosertib and IL-2) with NK cells will be safe and will activate the donor NK cells. NK cells and vactosertib are experimental because they are not approved by the Food and Drug Administration (FDA). IL-2 (Proleukin®) has been approved by the FDA for treating other cancers, but the doses used in this study are lower than the approved doses and it is not approved to treat colorectal cancer or blood cancers.

Official Title

A Phase Ib Study to Evaluate Safety and Persistence of ex Vivo Expanded Universal Donor NK Cells in Combination With IL-2 and TGFbeta Receptor I Inhibitor Vactosertib in Patients With Locally Advanced/Metastatic Colorectal Cancer, Gastric/Esophageal Cancer, and Relapsed/Refractory Hematologic Malignancies

Quick Facts

Study Start:2022-09-09
Study Completion:2026-06-01
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:SUSPENDED

Study ID

NCT05400122

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * Subjects must have one of the following:
  2. * Histologically confirmed locally advanced or metastatic colon or rectal adenocarcinoma
  3. * Histologically confirmed locally advanced or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma
  4. * Relapsed or refractory hematologic malignancy
  5. * Acute myeloid leukemia with measurable residual disease (MRD) relapse
  6. * MRD relapse is defined as presence of ≥ 1 in 10-4 nucleated cells per European LeukemiaNet 2021 guidance \[49\]: (1) conversion of MRD negativity to MRD positivity, independent of the MRD technique, or (2) increase of MRD ≥1 log10 between any two positive samples measured in the same tissue (PB or BM) in patients with MRD-Low Level
  7. * Patients will be eligible if they have declined or are ineligible for standard treatment options and if there is no standard approach to curative therapy per NCCN guidelines. Patients with solid tumors must have had progression on at least one standard line of therapy.
  8. * Hematologic malignancies in the relapsed or refractory setting can include:
  9. * Acute myeloid leukemia
  10. * Myelodysplastic syndrome
  11. * Acute lymphoblastic leukemia
  12. * Chronic myeloid leukemia
  13. * Chronic lymphocytic leukemia
  14. * Non Hodgkin Lymphoma
  15. * Hodgkin Lymphoma
  16. * Myeloproliferative syndromes
  17. * Plasma cell myeloma
  18. * Subjects must have recovered from acute toxicities of prior chemotherapy or stem cell transplant. Any prior non-hematologic vital organ toxicity (cardiac, pulmonary, hepatic, renal) of previous therapy must have resolved to grade 1 or less. Exceptions: Alopecia; subjects with chemotherapy-induced sensory neuropathy must have grade ≤ 3
  19. * Age ≥18 years. Because no dosing or adverse event data are currently available on the use of NK cells in subjects ≤18 years of age, children are excluded from this study.
  20. * Eastern Cooperative Oncology Group (ECOG) Performance status ≤2
  21. * Subjects must have normal organ and marrow function as defined below:
  22. * Serum total bilirubin \<2 mg/dl. If known Gilbert syndrome, total bilirubin must be \<3mg/dl
  23. * Aspartate aminotransferase (AST) \< 2.5 X institutional upper limit of normal
  24. * Alanine Aminotransferase (ALT) \< 2.5 X institutional upper limit of normal
  25. * Pulmonary function (DLCO) \>40% of the expected value corrected for alveolar volume and hemoglobin
  26. * Serum Creatinine ≤ 1.5 X institutional upper limit of normal
  27. * Hemoglobin ≥ 7.5 g/dL
  28. * Absolute neutrophil count ≥ 1,250/mcL for colorectal cancer (CRC) patients or ≥ 1,000/mcL for patients with hematologic malignancies unless patient has bone marrow involvement of hematological malignancy
  29. * Platelet count ≥ 50,000/mcL; unless patient has bone marrow involvement of hematological malignancy
  30. * For patients with bone marrow involvement of hematologic malignancy, transfusion of blood products may be used to meet hemoglobin and platelet thresholds
  31. * Women of child-bearing potential and men must agree to use adequate contraception (double barrier method of birth control or abstinence) 4 weeks prior to study entry and for the duration of study participation. Women of child-bearing potential must have documented negative pregnancy test prior to start of lymphodepleting regimen. Child-bearing potential is defined by institutional standard.
  32. * Subjects must have the ability to understand and the willingness to sign a written informed consent document.
  33. * Subjects must have at least 3 weeks between last cytotoxic anti-neoplastic medication and initiation of preparative regimen.
  1. * Subjects receiving any other investigational agents
  2. * Subjects requiring systemic corticosteroid therapy (10mg or less of prednisone or equivalent doses of other systemic steroids are permitted).
  3. * Subjects for whom a potential 29-day delay in treatment will interfere with their potential therapeutic options
  4. * Patients with active, untreated malignant involvement of the central nervous system (CNS) should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. If clinical suspicion for CNS involvement, head imaging will be necessary to document absence of active CNS involvement in patients with colorectal or esophagogastric cancer. Patients with hematologic malignancies who have undergone treatment for malignant involvement of the CNS must have no clinical evidence of residual CNS disease prior to study enrollment.
  5. * History of allergic reactions to fludarabine or cyclophosphamide
  6. * Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  7. * Pregnant or breastfeeding women are excluded from this study because cytotoxic agents used as part of the lymphodepleting regimen have the potential for teratogenic or abortifacient effects. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with lymphodepleting chemotherapy, breastfeeding should be discontinued if the mother participates in the trial. These potential risks may also apply to other agents used in this study.
  8. * HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with chemotherapeutic agents. In addition, these patients are at increased risk of lethal infections when treated with marrow suppressive therapy.
  9. * Chronic active untreated hepatitis B or C infection. (Assessments should include Hepatitis B Surface Ab, Hepatitis B Surface Ag, Hepatitis B Core Ab - Total, Hepatitis B Core Ab, IGM, Hepatitis C Ab).
  10. * Recipients of previous allogeneic transplants who have rash involving more than 10% body surface area attributed to graft versus host disease (GVHD). Stem cell transplant recipients will be excluded if they are still receiving immunosuppression including steroids for GVHD or have active GVHD in any organ (except for 10% BSA of skin, not requiring treatment).
  11. * Subject who is taking prohibited medications when using vactosertib as following (refer to APPENDIX III). A minimal washout period of 5 half-lives for the following drugs is recommended prior to the first dosing.
  12. * Concurrent use of drugs or foods that are known strong CYP3A4 inhibitors including but not limited to grapefruit juice, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, voriconazole. The topical use of these medications (if applicable), such as 2% ketoconazole cream, may be allowed.
  13. * Concurrent use of drugs that are known potent CYP3A4 inducers including but not limited to phenytoin, rifampin, St. John's wort.
  14. * Concurrent use of drugs that are CYP3A4, CYP1A2, CYP2B6 substrates with narrow therapeutic indices including but not limited to theophylline, astemizole, cisapride, cyclosporine, dihydroergotamine, ergotamine, sirolimus, tacrolimus, terfenadine (astemizole, cisapride, and terfenadine have been withdrawn from the US market).
  15. * Concurrent use of drugs that are sensitive CYP3A4, CYP1A2, CYP2B6 substrates including but not limited to efavirenz, darunavir, dasatinib, everolimus, lopinavir, midazolam, sirolimus, ticagrelor.
  16. * QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 12-lead ECGs

Contacts and Locations

Principal Investigator

Benjamin Tomlinson, MD
PRINCIPAL_INVESTIGATOR
University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Study Locations (Sites)

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
Cleveland, Ohio, 44106
United States

Collaborators and Investigators

Sponsor: David Wald

  • Benjamin Tomlinson, MD, PRINCIPAL_INVESTIGATOR, University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-09-09
Study Completion Date2026-06-01

Study Record Updates

Study Start Date2022-09-09
Study Completion Date2026-06-01

Terms related to this study

Additional Relevant MeSH Terms

  • Colorectal Cancer
  • Hematologic Malignancy
  • Rectum Cancer
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
  • Acute Lymphoblastic Leukemia
  • Chronic Myeloid Leukemia
  • Chronic Lymphocytic Leukemia
  • Hodgkin Lymphoma
  • Non Hodgkin Lymphoma
  • Myeloproliferative Syndrome
  • Plasma Cell Myeloma
  • Gastric Cancer
  • Esophageal Cancer
  • Esophagus Cancer
  • Gastric Cancer, Metastatic
  • Unresectable Esophageal Cancer
  • Metastatic Esophageal Cancer