Targeted treatment for high-risk acute leukemia and myelodysplastic syndrome

Phase I Study of Escalating Doses of 90Y-DOTA-Anti-CD25 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 Leukemia or Myelodysplastic Syndrome

This study is testing a new targeted treatment for people with high-risk acute leukemia or myelodysplastic syndrome to see if it can safely help them by killing cancer cells and improving their chances for a successful bone marrow transplant.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 60 Years and up
• Sex: All
• Sponsor: City of Hope Medical Center (other)
• Drugs / interventions: chemotherapy, radiation, methotrexate, basiliximab, fludarabine
• Locations: 1 site (Duarte, California)
• Trial ID: NCT05139004 on ClinicalTrials.gov

What this trial studies

This phase I trial investigates the safety and effectiveness of a targeted therapy using 90Y-DOTA-anti-CD25 basiliximab, combined with fludarabine, melphalan, and total marrow and lymphoid irradiation (TMLI) for patients with high-risk acute leukemia or myelodysplastic syndrome. The study aims to determine the maximum tolerated dose of the treatment and assess its side effects, overall survival, and other key outcomes. By using a monoclonal antibody linked to a radioactive agent, the approach seeks to selectively target and kill cancer cells while preparing the bone marrow for transplantation.

Who should consider this trial

Good fit: Ideal candidates include patients aged 60 and older with high-risk acute leukemia or myelodysplastic syndrome who are not eligible for standard myeloablative regimens.

Not a fit: Patients with low-risk leukemia or those who are candidates for standard myeloablative conditioning regimens may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve transplant outcomes and survival rates for patients with high-risk hematologic malignancies.

How similar studies have performed: While this approach is innovative, similar targeted therapies have shown promise in other studies, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

* 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)
* Patients must have a serum bilirubin =\< 2.0 mg/dl (performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
* Serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) =\< 2.5 times the institutional upper limits of normal (performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
* Ejection fraction measured by echocardiogram or multigated acquisition scan (MUGA) \>= 50% (performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
* Diffusion capacity of the lung for carbon monoxide (DLCO) and forced expiratory volume in 1 second (FEV1) \> 50% predicted (performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
* 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

  * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)

Exclusion Criteria:

* 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
* All patients with prior radiation treatment to the lung, liver, and kidney will be excluded. For other scenarios of prior radiation treatment, up to 2000 cGy at 2 Gy per day will be allowed. Inclusion of patients with previous radiation exposure will be determined based on the radiation oncologist medical doctor (MD) evaluation and judgment
* 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

Where this trial is running

Duarte, California

• City of Hope Medical Center — Duarte, California, United States (RECRUITING)

Study contacts

• Principal investigator: Jeffrey Y Wong — City of Hope Medical Center

Conditions: Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Myelodysplastic Syndrome, Secondary Acute Myeloid Leukemia