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

NCT05139004 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 21016NCI-2021-05555P30CA033572
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Myelodysplastic Syndrome; Secondary Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose/recommended phase II dose of 90Y-DOTA-antiradioimmunotherapy

  Up to 30 days post stem cell infusion

• Incidence of toxicity

  Toxicity will be scored on both the Bearman Scale and National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5 Scale.

  Up to 30 days post-transplant

Secondary Outcomes (11)

• Overall survival

  From start of protocol therapy to death, or last follow-up, whichever comes first, assessed up to 2 years

• Event-free survival

  From start of protocol therapy to death, relapse/progression, or last follow-up, whichever comes first, assessed up to 2 years

• Relapse/progression

  From start of therapy up to 2 years post stem cell infusion

• Graft versus host disease and relapse free survival

  From start of therapy up to 2 years post-transplant

• Complete remission (CR) proportion at day +30

  From the start of therapy to the time of biopsy proven CR, assessed at 30 days

Study Arms (1)

Treatment (90Y-basiliximab, fludarabine, melphalan, TMLI)

EXPERIMENTAL

Patients receive cold basiliximab IV, 111In-DOTA-anti-CD25 basiliximab IV, and 90Y-DOTA-anti-CD25 basiliximab IV on day -15. Patients also receive palifermin IV on days -11 to -9, fludarabine phosphate IV on days -4 to -2, melphalan IV on day -2, and undergo TMLI on days -8 to -5 in the absence of disease progression or unacceptable toxicity. Patients then undergo AHSCT on day 0.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Biological: Basiliximab; Drug: Fludarabine Phosphate; Drug: Indium In 111-DOTA-Basiliximab; Drug: Melphalan; Biological: Palifermin; Radiation: Total Lymphoid Irradiation; Radiation: Total Marrow Irradiation; Biological: Yttrium Y 90 Basiliximab

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo AHSCT

Also known as: Allogeneic, Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT, Stem Cell Transplantation, Allogeneic

Treatment (90Y-basiliximab, fludarabine, melphalan, TMLI)

Basiliximab BIOLOGICAL

Given IV

Also known as: SDZ-CHI-621, Simulect

Treatment (90Y-basiliximab, fludarabine, melphalan, TMLI)

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586

Treatment (90Y-basiliximab, fludarabine, melphalan, TMLI)

Indium In 111-DOTA-Basiliximab DRUG

Given IV

Also known as: 111In-DOTA-Basiliximab

Treatment (90Y-basiliximab, fludarabine, melphalan, TMLI)

Melphalan DRUG

Given IV

Also known as: Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard, L-Sarcolysin, L-Sarcolysin Phenylalanine mustard, L-Sarcolysine, Melphalanum, Phenylalanine Mustard, Phenylalanine Nitrogen Mustard, Sarcoclorin, Sarkolysin, WR-19813

Treatment (90Y-basiliximab, fludarabine, melphalan, TMLI)

Palifermin BIOLOGICAL

Given IV

Also known as: Growth Factor, Recombinant Human Keratinocyte, Kepivance, Keratinocyte Growth Factor, Recombinant Human, Recombinant Human Keratinocyte Growth Factor, rhKGF, rhu Keratinocyte Growth Factor

Treatment (90Y-basiliximab, fludarabine, melphalan, TMLI)

Total Lymphoid Irradiation RADIATION

Undergo TMLI

Also known as: TLI

Treatment (90Y-basiliximab, fludarabine, melphalan, TMLI)

Total Marrow Irradiation RADIATION

Undergo TMLI

Treatment (90Y-basiliximab, fludarabine, melphalan, TMLI)

Yttrium Y 90 Basiliximab BIOLOGICAL

Given IV

Also known as: 90Y Basiliximab, Yttrium Y 90-DOTA-Basiliximab

Treatment (90Y-basiliximab, fludarabine, melphalan, TMLI)

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative
• Assent, when appropriate, will be obtained per institutional guidelines
• Age: \>= 60 years. Note: Patients \>= 18 years and \< 60 years are also included if they are not candidates for myeloablative conditioning regimens due to comorbidities
• Karnofsky performance status \>= 70
• Eligible patients will have a histopathological confirmed diagnosis of hematologic malignancy in one of the following categories which express CD25 as determined by immunohistochemistry:
• Acute myelogenous leukemia:
• Patients with de novo or secondary disease in unfavorable risk group including poor risk cytogenetics according to National Comprehensive Cancer Network (NCCN) guidelines for acute myeloid leukemia (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
• Patients with a complete morphological remission (CR) with minimal residual disease (MRD)-positive status by flow cytometry or cytogenetic
• Patients with chemosensitive active disease
• Acute lymphocytic leukemia:
• Patients with de novo or secondary disease according to NCCN guidelines for acute lymphocytic leukemia (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
• Patients with a complete morphological remission (CR) with MRD-positive status by flow cytometry or cytogenetics
• Patients with chemosensitive active disease
• Myelodysplastic syndrome in high-intermediate (int-2) and high-risk categories
• A pretreatment measured creatinine clearance (absolute value) of \>= 60 ml/minute (performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)

You may not qualify if:

• Autologous or allogeneic hematopoietic cell transplant
• Patients may not have received more than 3 prior regimens, where the regimen intent was to induce remission
• Receiving any other investigational agents or concurrent biological, intensive chemotherapy or radiation therapy for the previous 2 weeks from conditioning. Note: Receiving any other investigational agents or concurrent biological, intensive chemotherapy or radiation therapy for the previous 2 weeks from conditioning
• 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
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
• Patients with other active malignancies are ineligible for this study, other than non-melanoma skin cancers
• Patients should not have any uncontrolled illness including ongoing or active bacterial, viral or fungal infection
• 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 principal investigator would place the recipient at unacceptable risk
• Females only: Pregnant or breastfeeding
• 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
• 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)
• DONOR: Evidence of active infection
• DONOR: Medical or physical reason which makes the donor unlikely to tolerate or cooperate with growth factor therapy and leukapheresis
• DONOR: Factors which place the donor at increased risk for complications from leukapheresis or granulocyte-colony stimulating factor (G-CSF) therapy could be harvested for bone marrow (BM) if safer for the donor and if approved by principal investigator (PI)
• DONOR: Human immunodeficiency virus (HIV) positive

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Stem Cell Transplantation; Basiliximab; fludarabine phosphate; Indium; Melphalan; Fibroblast Growth Factor 7

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Metals, Heavy; Elements; Inorganic Chemicals; Metals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Fibroblast Growth Factors; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors

Study Officials

• Jeffrey Y Wong

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2021
• First Posted: December 1, 2021
• Study Start: July 19, 2022
• Primary Completion (Estimated): June 13, 2027
• Study Completion (Estimated): June 13, 2027
• Last Updated: July 8, 2025

Record last verified: 2025-07

Locations

US (1)