Radioimmunotherapy + Chemotherapy for Leukemia

Recruiting in Palo Alto (17 mi)

Overseen by Jeffrey Y Wong

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: City of Hope Medical Center

Must not be taking: Investigational agents

Disqualifiers: Transplant, Active malignancies, Uncontrolled illness, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests a combination of a special antibody with radiation, chemotherapy, and targeted radiation therapy. It is aimed at patients with high-risk leukemia or myelodysplastic syndrome who can't have standard treatments. The treatment targets cancer cells directly and prepares the body for a stem cell transplant.

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.

What data supports the effectiveness of the treatment Radioimmunotherapy + Chemotherapy for Leukemia?

Research shows that radioimmunotherapy, which combines targeted radiation with antibodies, has been effective in treating blood cancers like B-cell lymphomas, achieving high response rates. Although specific data for leukemia is limited, similar treatments have shown promise in related conditions, suggesting potential effectiveness. ^{1 2 3 4 5}

Is radioimmunotherapy generally safe for humans?

Studies on radioimmunotherapy, such as those using 90Y-ibritumomab tiuxetan, have shown that while there are some side effects like blood-related issues, they are generally manageable and the treatment is considered safe for certain types of lymphoma. ^{1 4 5 6 7}

What makes the treatment 90Y-DOTA-anti-CD25 Basiliximab unique for leukemia?

This treatment combines radioimmunotherapy, which uses a radioactive substance attached to an antibody to target cancer cells, with chemotherapy drugs like Fludarabine and Melphalan. The unique aspect is the use of 90Y-DOTA-anti-CD25 Basiliximab, which specifically targets the CD25 protein on leukemia cells, potentially offering a more precise attack on the cancer compared to traditional chemotherapy alone. ^{2 5 8 9 10}

Research Team

Jeffrey Y Wong

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• 90Y-DOTA-anti-CD25 Basiliximab (Radioactive Agent)
• Allogeneic Hematopoietic Stem Cell Transplantation (Procedure)
• Basiliximab (Monoclonal Antibodies)
• Fludarabine Phosphate (Chemotherapy Drugs)
• Melphalan (Chemotherapy Drugs)
• Total Lymphoid Irradiation (Radiation)
• Total Marrow Irradiation (Radiation)

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.

Participant Groups

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+

Robert Stone

City of Hope Medical Center

Chief Executive Officer since 2014

Juris Doctorate from the University of Chicago, Bachelor's degree in Political Science from the University of Redlands

Sumanta (Monty) Pal

City of Hope Medical Center

Chief Medical Officer since 2023

MD

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. England 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. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Review of clinical radioimmunotherapy. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Recent progress in radioimmunotherapy for cancer. [2005]

4. England 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. [2020]

5. England 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. [2018]

6. United States 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. [2016]

7. England pubmed.ncbi.nlm.nih.gov

Consolidation with 90 Yttrium-ibritumomab tiuxetan after bendamustine and rituximab for relapsed follicular lymphoma. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Biokinetics and dosimetry of 188Re-anti-CD20 in patients with non-Hodgkin's lymphoma: preliminary experience. [2015]

9. United States 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. [2015]

10. United States pubmed.ncbi.nlm.nih.gov

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