RECRUITING

225Ac-DOTA-Anti-CD38 Daratumumab Monoclonal Antibody With Fludarabine, Melphalan and Total Marrow and Lymphoid Irradiation as Conditioning Treatment for Donor Stem Cell Transplant in Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia and Myelodysplastic Syndrome

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Conditions

Acute Lymphoblastic LeukemiaAcute Myeloid LeukemiaMyelodysplastic Syndrome

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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

This phase I trial tests the safety, side effects, best dose, and effectiveness of 225Ac-DOTA-Anti-CD38 daratumumab monoclonal antibody in combination with fludarabine, melphalan and total marrow and lymphoid irradiation (TMLI) as conditioning treatment for donor stem cell transplant in patients with high-risk acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) and myelodysplastic syndrome (MDS). Daratumumab is in a class of medications called monoclonal antibodies. It binds to a protein called CD38, which is found on some types of immune cells and cancer cells. Daratumumab may block CD38 and help the immune system kill cancer cells. Radioimmunotherapy is treatment with a radioactive substance that is linked to a monoclonal antibody, such as daratumumab, that will find and attach to cancer cells. Radiation given off by the radioisotope my help kill the cancer cells. Chemotherapy drugs, such as fludarabine and melphalan, 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. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. TMLI is a targeted form of body radiation that targets marrow, lymph node chains, and the spleen. It is designed to reduce radiation-associated side effects and maximize therapy effect. Actinium Ac 225-DOTA-daratumumab combined with fludarabine, melphalan and TMLI may be safe, tolerable, and/or effective as conditioning treatment for donor stem cell transplant in patients with high-risk AML, ALL, and MDS.

Official Title

Phase I Study of Escalating Doses of 225Ac-DOTA-Anti-CD38 Daratumumab Monoclonal Antibody Added to the Conditioning Regimen of Fludarabine, Melphalan and Organ Sparing Total Marrow and Lymphoid Irradiation (TMLI) as Conditioning for Allogeneic Hematopoietic Cell Transplantation in Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia and Myelodysplastic Syndrome

Quick Facts

Study Start:2025-01-18
Study Completion:2028-05-19
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT06287944

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. * Documented informed consent of the participant and/or legally authorized representative
  2. * Assent, when appropriate, will be obtained per institutional guidelines
  3. * ≥ 60 years. Note: Patients ≥ 18 years and \< 60 years with HCT-comorbidity index (CI) ≥ 2 are also included
  4. * Karnofsky performance status ≥ 70
  5. * Eligible patients will have a histopathological confirmed diagnosis of hematologic malignancy in one of the following categories :
  6. * Acute myelogenous leukemia:
  7. * Patients with de novo or secondary disease in unfavorable risk group including poor risk cytogenetics according to National Comprehensive Cancer Network (NCCN) guidelines for AML i.e., monosomal karyotype, -5,5q-,-7,7q-,11q23-non t(9;11), inv (3), t(3;3), t(6;9), t(9;22) and complex karyotypes (≥ 3 unrelated abnormalities), or all patient in intermediate risk groups accept patients with FLT3-NPM1+ disease, OR
  8. * Patients with a complete morphological remission (CR) with minimal residual disease (MRD)-positive status by flow cytometry (≥ 0.1% by flow cytometry) or cytogenetic after at least 2 prior induction therapies, OR
  9. * Patients with chemosensitive active disease defined as at least 50% reduction in their blast count after last treatment
  10. * Myelodysplastic syndrome in high-intermediate (int-2) and high-risk categories per Revised International Prognostic Scoring System- (IPSS-R)
  11. * Acute lymphocytic leukemia
  12. * Patients with de novo or secondary disease according to NCCN guidelines for ALL hypoploidy (\< 44 chromosomes); t(v;11q23): MLL rearranged; t(9;22) (q34;q11.2); complex cytogenetics (5 or more chromosomal abnormalities); high white blood cell (WBC) at diagnosis (≥ 30,000 for B lineage or ≥ 50,000 for T lineage); iAMP21loss of 13q, and abnormal 17p, OR
  13. * Patients with a complete response (CR) with MRD-positive status by flow cytometry (≥ 0.1% by flow cytometry) or cytogenetics after at least 2 prior induction therapies, OR
  14. * Patients with chemosensitive active disease defined as at least 50% reduction in their blast count after last treatment
  15. * A pretreatment measured creatinine clearance (absolute value) of ≥ 60 ml/minute (To be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
  16. * Patients must have a serum bilirubin ≤ 2.0 mg/dl (To be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
  17. * Patients must have a serum glutamic oxaloacetic transaminase (SGOT) ≤ 2.5 times the institutional upper limits of normal (To be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
  18. * Patients must have a serum glutamic pyruvic transaminase (SGPT) ≤ 2.5 times the institutional upper limits of normal (To be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
  19. * Ejection fraction measured by echocardiogram or multigated acquisition scan (MUGA) ≥ 50% (To be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
  20. * Diffusion capacity of the lung for carbon monoxide (DLCO) \> 50% predicted (To be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
  21. * Forced expiratory volume in 1 second (FEV1) \> 50% predicted (To be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
  22. * Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of protocol therapy
  23. * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)
  24. * DONOR SPECIFIC CRITERIA: All candidates for this study must have an human leukocyte antigen (HLA) (A, B, C, and DR) identical sibling who is willing to donate mobilized peripheral blood stem cells (preferred) or bone marrow, or have a 10/10 (A, B, C, DR and DQ) allele matched unrelated donor. DQ or DP mismatch is allowed per discretion of the principal investigator. City of Hope (COH) standards of practice (SOP) (B.001.11) will be used for allogeneic donor evaluation, selection, and consent. Donor screening will be in compliance with all requirements of Food and Drug Administration (FDA) regulation 21 CFR Part 1271 including donor screening for COVID-19 exposure or infection
  1. * Patients who had a prior allogeneic transplant
  2. * All patients with prior radiation treatment to the lung, liver, and kidney
  3. * Patients who have received prior radiopharmaceutical therapy
  4. * Inclusion of other patients with previous radiation exposure will be determined based on the radiation oncologist medical doctor (MD) principal investigator (PI) evaluation and judgement
  5. * For patients with leukemia or MDS: Patients may not have received more than 3 prior regimens, where the regimen intent was to induce remission
  6. * Receiving any other investigational agents or concurrent biological, intensive chemotherapy or radiation therapy for the previous 2 weeks from conditioning
  7. * Patients should have discontinued all previous intensive therapy, chemotherapy, or radiotherapy for 2 weeks prior to commencing therapy on this study. Note: Low dose chemotherapy or maintenance chemotherapy given within 7 days of planned study enrollment is permitted. These include hydroxyurea, 6-meraptopurine, oral methotrexate, vincristine, oral etoposide, and tyrosine kinase inhibitors (TKIs). FLT-3 inhibitors can also be given up to 3 days before conditioning regimen
  8. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
  9. * Patients with other active malignancies are ineligible for this study, other than non-melanoma skin cancers
  10. * Patients should not have any uncontrolled illness including ongoing or active bacterial, viral or fungal infection
  11. * The recipient has a medical problem or neurologic/psychiatric dysfunction which would impair his/her ability to be compliant with the medical regimen and to tolerate transplantation or would prolong hematologic recovery which in the opinion of the investigator (treating physician) would place the recipient at unacceptable risk
  12. * Females only: Pregnant or breastfeeding
  13. * Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
  14. * Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Contacts and Locations

Principal Investigator

Jeffrey Y Wong
PRINCIPAL_INVESTIGATOR
City of Hope Medical Center

Study Locations (Sites)

City of Hope Medical Center
Duarte, California, 91010
United States

Collaborators and Investigators

Sponsor: City of Hope Medical Center

  • Jeffrey Y Wong, PRINCIPAL_INVESTIGATOR, City of Hope Medical 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 Date2025-01-18
Study Completion Date2028-05-19

Study Record Updates

Study Start Date2025-01-18
Study Completion Date2028-05-19

Terms related to this study

Additional Relevant MeSH Terms

  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndrome