Radioimmunotherapy + Chemotherapy for Leukemia

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: Investigational agents

Disqualifiers: Transplant, Active malignancies, Uncontrolled illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 15 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment plan for individuals with high-risk acute leukemia or myelodysplastic syndrome. The study combines a special antibody linked to a radioactive agent (radioimmunotherapy) with traditional chemotherapy and a specific type of radiation therapy to determine if it better prepares the bone marrow for cell transplants. Participants must have a confirmed diagnosis of these blood disorders and some remaining cancer cells after initial treatments. The main goal is to identify the optimal dose and assess any benefits or side effects of this new combination therapy. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial requires that participants stop intensive therapy, chemotherapy, or radiotherapy for 2 weeks before starting the study. However, low dose or maintenance chemotherapy like hydroxyurea and certain other medications are allowed within 7 days of enrollment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that 90Y-DOTA-anti-CD25 basiliximab is safe and tolerable. A previous study found it was well-received by patients with relapsed or hard-to-treat peripheral T-cell lymphoma (PTCL), meaning it did not cause severe side effects.

Fludarabine phosphate has been used and studied in over 3,000 patients with various types of cancer. Common side effects include low white blood cell counts, but these effects usually resolve over time.

Melphalan is another common chemotherapy drug. Studies confirm that its safety is well understood, with side effects similar to other treatments.

This trial is in an early phase, focusing on finding the best dose and understanding side effects. A data safety and monitoring board will oversee the trial to ensure patient safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for leukemia because it combines radioimmunotherapy with chemotherapy, offering a potentially powerful dual approach. Unlike traditional treatments, this therapy uses 90Y-DOTA-anti-CD25 basiliximab, which is a radio-labeled antibody targeting CD25 on leukemia cells. This targets the cancer cells directly, possibly increasing effectiveness while minimizing damage to healthy cells. Additionally, the combination of fludarabine and melphalan with targeted radiation could enhance the overall cancer-killing ability, offering hope for improved outcomes.

What evidence suggests that this trial's treatments could be effective for leukemia?

Research has shown that 90Y-DOTA-anti-CD25 basiliximab, which participants in this trial may receive, targets specific cancer cells and delivers radiation directly to destroy them. Early studies indicated that this method was safe and manageable for patients with similar conditions, such as high-risk Hodgkin lymphoma. Fludarabine, another treatment option in this trial, has demonstrated an overall success rate of up to 80.2% in some studies, effectively treating certain blood cancers. When used in high doses, Melphalan, also part of this trial, has resulted in a high rate of complete response, meaning many patients see their cancer disappear or significantly shrink. Together, these treatments aim to prepare the bone marrow for a transplant, potentially improving outcomes for patients with acute leukemia or myelodysplastic syndrome. ^{1 2 3 4 6}

Who Is on the Research Team?

Jeffrey Y Wong

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with high-risk acute leukemia or myelodysplastic syndrome who are not candidates for intensive treatment due to age or comorbidities. Participants must have CD25 positive cancer cells, adequate organ function, and agree to birth control measures. Those with more than three prior treatments, uncontrolled infections, recent intensive therapies, or unable to comply with study procedures are excluded.

Inclusion Criteria

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

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)

I am able to care for myself but may not be able to do active work.

Exclusion Criteria

I do not have any uncontrolled illnesses or infections.

I have had a stem cell transplant using my own or donor cells.

I have had 3 or fewer treatments aimed at curing my condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cold basiliximab, 111In-DOTA-anti-CD25 basiliximab, and 90Y-DOTA-anti-CD25 basiliximab, along with fludarabine, melphalan, and TMLI, followed by allogeneic hematopoietic stem cell transplantation

15 days

Daily visits for treatment administration

Follow-up

Participants are monitored for safety, effectiveness, and adverse events, including GVHD and infections

Up to 2 years

Regular follow-up visits, frequency not specified

Long-term follow-up

Participants are monitored for overall survival, event-free survival, and relapse/progression

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• 90Y-DOTA-anti-CD25 Basiliximab
• Allogeneic Hematopoietic Stem Cell Transplantation
• Basiliximab
• Fludarabine Phosphate
• Melphalan
• Total Lymphoid Irradiation
• Total Marrow Irradiation

Trial Overview The trial tests a combination of the radioactive antibody 90Y-DOTA-anti-CD25 basiliximab with chemotherapy drugs fludarabine and melphalan, plus total marrow and lymphoid irradiation (TMLI). It aims to determine the best dose and assess potential benefits and side effects in preparation for stem cell transplantation.

How Is the Trial Designed?

Group I: Treatment (90Y-basiliximab, fludarabine, melphalan, TMLI) Experimental Treatment 9 Interventions

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.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a phase 2 trial involving 71 elderly patients with untreated diffuse large B-cell lymphoma, fractionated radioimmunotherapy using 90Y-epratuzumab tetraxetan showed a promising 2-year event-free survival rate of 75%, indicating its potential as a consolidation treatment after initial chemotherapy.

However, the treatment was associated with significant toxicity, including severe thrombocytopenia in 84% of patients and neutropenia in 79%, highlighting the need for careful monitoring and further studies to assess the balance between efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consolidation anti-CD22 fractionated radioimmunotherapy with 90Y-epratuzumab tetraxetan following R-CHOP in elderly patients with diffuse large B-cell lymphoma: a prospective, single group, phase 2 trial. Kraeber-Bodere, F., Pallardy, A., Maisonneuve, H., et al.[2019]

In a study of 9 patients with recurrent follicular lymphoma, treatment with 4 cycles of FCR followed by radioimmunotherapy (90Y-RIT) showed long-term efficacy, with 67% overall and progression-free survival rates at 7.5 years.

The treatment was generally safe, with the most common severe side effects being hematologic, and no unexpected toxicities were reported, making it a viable option for patients aged 60-75.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long term efficacy and safety of Fludarabine, Cyclophosphamide and Rituximab regimen followed by (90)Y-ibritumomab tiuxetan consolidation for the treatment of relapsed grades 1 and 2 follicular lymphoma. Pisani, F., Sciuto, R., Dessanti, ML., et al.[2020]

The study developed (177)Lu-CHX-A"-DTPA-Rituximab, a radioimmunotherapy agent that effectively targets CD20 antigens in B-cell lymphomas, showing over 95% radiochemical purity and significant binding to Raji cells in vitro.

Biodistribution studies in SCID mice demonstrated good tumor uptake of the agent, indicating its potential as a promising treatment for non-Hodgkin's lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and Preclinical Evaluation of (177)Lu-CHX-A"-DTPA-Rituximab as a Radioimmunotherapeutic Agent for Non-Hodgkin's Lymphoma. Kameswaran, M., Pandey, U., Dhakan, C., et al.[2015]

In a study of 24 patients with relapsed follicular lymphoma (FL), consolidation therapy with 90 Yttrium-ibritumomab tiuxetan (90 Y-IT) after re-induction with bendamustine and rituximab (BR) resulted in a 2-year progression-free survival (PFS) rate of 59%, indicating its potential effectiveness as a treatment option.

While hematological toxicities were the main adverse events observed, they were generally acceptable, and the overall survival rate after consolidation was high at 95%, suggesting that 90 Y-IT consolidation is a safe and promising strategy for achieving durable remission in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consolidation with 90 Yttrium-ibritumomab tiuxetan after bendamustine and rituximab for relapsed follicular lymphoma. Miura, K., Tsujimura, H., Masaki, Y., et al.[2021]

Radioimmunotherapy combines targeted monoclonal antibodies with radioactive isotopes to effectively treat indolent B-cell lymphoma, achieving 20-40% complete response rates and 60-80% overall response rates with mild toxicity.

Current research aims to expand the use of radioimmunotherapy to other CD20+ diseases and solid tumors, exploring enhancement methods to improve response rates, with early-stage trials already underway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of clinical radioimmunotherapy. Pohlman, B., Sweetenham, J., Macklis, RM.[2022]

The study established that (188)Re-anti-CD20, a targeted radiopharmaceutical, can deliver an absorbed dose of 0.75 Gy to the total body, which aligns with the recommended dosage for treating non-Hodgkin's lymphoma (NHL).

These promising dosimetric results support further clinical evaluation of (188)Re-anti-CD20 to assess its safety, toxicity, and efficacy in patients with NHL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biokinetics and dosimetry of 188Re-anti-CD20 in patients with non-Hodgkin's lymphoma: preliminary experience. Torres-García, E., Ferro-Flores, G., Arteaga de Murphy, C., et al.[2015]

Radioimmunotherapy has shown significant success in treating chemotherapy-resistant B-cell lymphomas, achieving high complete remission rates, especially when combined with stem-cell transplants.

While solid tumors have been more challenging to treat, regional administration methods have yielded promising results, particularly for small tumor burdens, highlighting the need for ongoing research to improve targeting and administration techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent progress in radioimmunotherapy for cancer. Meredith, RF., LoBuglio, AF., Spencer, EB.[2005]

Radioimmunotherapy (RIT) is a promising treatment for tumors, particularly effective against B-cell non-Hodgkin lymphoma (NHL), with two agents, Zevalin and Bexxar, approved for use.

Both Zevalin and Bexxar target the CD20 antigen on B cells, achieving notable clinical outcomes with complete response rates of 20%-40% and overall response rates of 60%-80% in patients with indolent B-cell NHL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radioimmunotherapy as a therapeutic option for Non-Hodgkin's lymphoma. Macklis, RM.[2019]

In a phase 1 study involving 17 adults with relapsed or refractory B-cell acute lymphoblastic leukaemia, the radioimmunotherapy (90)Y-DOTA-epratuzumab was found to be well tolerated, with no maximum tolerated dose reached during the trial.

The most common serious side effects included pancytopenia and infections, particularly at the highest dose level, but overall, the treatment showed a favorable safety profile, leading to a recommended dose for future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

(90)Y-labelled anti-CD22 epratuzumab tetraxetan in adults with refractory or relapsed CD22-positive B-cell acute lymphoblastic leukaemia: a phase 1 dose-escalation study. Chevallier, P., Eugene, T., Robillard, N., et al.[2018]

In a study of 60 patients with symptomatic or bulky follicular lymphoma, a combination of short-course chemoimmunotherapy (CHOP-R) followed by radioimmunotherapy (RIT) led to a significant increase in complete response (CR) rates, from 40% after CHOP-R to 82% after RIT, as assessed by imaging.

The study found that patients who did not achieve a complete metabolic response on PET imaging after CHOP-R had a higher risk of relapse, highlighting the importance of early PET assessment in predicting treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of short-course CHOP-R followed by 90Y-ibritumomab tiuxetan and extended rituximab in previously untreated follicular lymphoma. Jacobs, SA., Swerdlow, SH., Kant, J., et al.[2016]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05139004

90Y-DOTA-anti-CD25 Basiliximab, Fludarabine, Melphalan ... 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, ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-05555

90Y-DOTA-anti-CD25 Basiliximab, Fludarabine, Melphalan ... 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, ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9153018/

Anti-CD25 radioimmunotherapy with BEAM autologous ... 90Y-antiCD25 aTac-BEAM AHCT was safe and tolerable in patients with high-risk R/R HL. aTac-BEAM AHCT was associated with favorable outcomes ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05139004?cond=%22Acute%20Leukemia%22&intr=%22chelating%20agents%22&viewType=Table&rank=3

90Y-DOTA-anti-CD25 Basiliximab, Fludarabine, Melphalan, and ... It identifies the role of the intervention that participants receive. Types of arms include experimental arm, active comparator arm, placebo comparator arm, ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11415869/

Yttrium-90 anti-CD25 BEAM conditioning for autologous ... Based on biodistribution data, a 90Y-basiliximab/DOTA dose of 0.6 mCi/kg delivers lower radiation doses to vital organs including the heart, lungs, kidneys, ...

6. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05139004/90y-dota-anti-cd25-basiliximab-fludarabine-melphalan-and-total-marrow-and-lymphoid-irradiation-for-the-treatment-of-high-risk-acute-leukemia-or-myelodysplastic-syndrome

90Y-DOTA-anti-CD25 Basiliximab, Fludarabine, Melphalan ... 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 ...