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.
PRIMARY OBJECTIVES: I. Describe toxicities attributable to 90Y-DOTA-anti-CD25 basiliximab radioimmunotherapy by dose level in patients treated under this regimen. II. Determine the maximum tolerated dose/recommended phase II dose (MTD/RP2D) of 90Y-DOTA-antiCD25 basiliximab radioimmunotherapy with fixed doses of organ sparing TMLI (12 Gy), fludarabine and melphalan (FM100) as conditioning regimen for allogeneic hematopoietic cell transplantation (HCT) for treatment of high-risk acute leukemias or myelodysplastic syndrome (MDS) in patients who are not eligible for standard myeloablative regimens. SECONDARY OBJECTIVES: I. Evaluate the safety of the regimen, at each dose level, by assessing the following: Ia. Type, frequency, severity, attribution, time course and duration of adverse events, including acute/chronic graft versus host disease (GVHD), infection and delayed engraftment. II. Estimate overall survival (OS), event-free survival (EFS), GVHD relapse free survival (GRFS), cumulative incidence (CI) of relapse/progression, and non-relapse mortality (NRM) at 100 days, 1 year and 2 years. III. Describe biodistribution, pharmacokinetics and organ dosimetry of 90Y-DOTA-basiliximab. OUTLINE: This is a dose-escalation study of 90Y-DOTA-anti-CD25 basiliximab. Patients receive cold basiliximab intravenously (IV), 111In-DOTA-anti-CD25 basiliximab IV, 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 allogeneic hematopoietic stem cell transplantation (AHSCT) on day 0. After completion of study treatment, patients are followed up for up to 2 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
7
Undergo AHSCT
Given IV
Given IV
Given IV
Given IV
Given IV
Undergo TMLI
Undergo TMLI
Given IV
City of Hope Medical Center
Duarte, California, United States
Maximum tolerated dose/recommended phase II dose of 90Y-DOTA-antiradioimmunotherapy
Time frame: 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.
Time frame: Up to 30 days post-transplant
Overall survival
Survival estimates will be calculated using the Kaplan-Meier method.
Time frame: From start of protocol therapy to death, or last follow-up, whichever comes first, assessed up to 2 years
Event-free survival
Survival estimates will be calculated using the Kaplan-Meier method.
Time frame: From start of protocol therapy to death, relapse/progression, or last follow-up, whichever comes first, assessed up to 2 years
Relapse/progression
The cumulative incidence of relapse/progression will be calculated as competing risks.
Time frame: From start of therapy up to 2 years post stem cell infusion
Graft versus host disease and relapse free survival
The event is relapse/progression, acute grade 3 or 4 graft versus host disease (GVHD), or chronic GVHD requiring systemic therapy. Death without relapse/progression, acute grade 3 or 4 GVHD or chronic GVHD requiring systemic therapy is considered a competing risk. Surviving patients with no history of relapse/progression or GVHD are censored at time of last follow-up.
Time frame: From start of therapy up to 2 years post-transplant
Complete remission (CR) proportion at day +30
Time frame: From the start of therapy to the time of biopsy proven CR, assessed at 30 days
Non-relapse mortality
The cumulative incidence of non-relapse will be calculated as competing risks.
Time frame: From start of therapy until non-disease related death, or last follow-up, whichever comes first, assessed up to 2 years
Incidence of Infection
Microbiologically documented infections will be reported by site of disease, date of onset, severity and resolution, if any. These data will be captured via case report form and will be collected from day 0 until 100 days post-transplant.
Time frame: Up to 100 days post-transplant
Incidence of toxicities/adverse events
Will only collect the highest grade of toxicities that meet grade 3, 4, or 5 per Bearman Scale and CTCAE v 4.03 from day -9 to day -1, from day 0 to day +30, and again from day +31 to +100 post-transplant.
Time frame: Up to 100 days -post-transplant
Neutrophil recovery
Measured from stem cell infusion to the first to three consecutive days with neutrophil count greater than 0.5x10\^9/l.
Time frame: From stem cell infusion up to 3 days
Incidence of acute graft versus host disease (GVHD) of grades 2-4 and 3-4
The cumulative incidence of acute GVHD will be calculated as competing risks.
Time frame: From date of stem cell infusion to document/biopsy proven acute GVHD onset date, assessed up to 100 days
Incidence of chronic GVHD
The cumulative incidence of chronic GVHD will be calculated as competing risks.
Time frame: From approximately 80-100 days post-transplant to the documented/biopsy proven chronic GVHD onset date
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