Moxetumomab + Rituximab/Ruxience for Hairy Cell Leukemia

Overseen By Robert J Kreitman, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Investigational agents, High dose estrogen

Disqualifiers: Brain metastases, Active infection, Uncontrolled hypertension, others

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

Compensation: Varies

Number of Visits: 2

Duration: Up to 32 weeks

18 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you've had chemotherapy, immunotherapy, or radiotherapy within 4 weeks, or rituximab/Ruxience within the last 3 months before starting the trial.

What data supports the effectiveness of the drug Moxetumomab Pasudotox-tdfk for treating hairy cell leukemia?

Moxetumomab pasudotox has been shown to be effective for patients with relapsed or refractory hairy cell leukemia, achieving a durable complete response in about 30% of patients in a phase III trial. It is approved by the FDA for patients who have not responded to at least two prior treatments. ^{1 2 3 4 5}

What safety data exists for Rituximab and its biosimilars?

Rituximab and its biosimilars, like HLX01, have been studied for safety in various conditions, including lymphoma. Studies show that the safety profile of Rituximab is generally comparable to its biosimilars, with a similar incidence of treatment-related adverse events. ^{6 7 8 9 10}

How is the drug Moxetumomab Pasudotox-tdfk unique for treating hairy cell leukemia?

Moxetumomab Pasudotox-tdfk is unique because it is a first-in-class drug that targets CD22 on cancer cells, leading to their death, and is specifically approved for patients with hairy cell leukemia who have not responded to at least two prior treatments. It offers a new option for achieving durable remission in patients who have relapsed or are refractory to other therapies. ^{1 2 3 4 11}

What is the purpose of this trial?

Background: Hairy cell leukemia (HCL) is a rare, slow-growing blood cancer in which the bone marrow makes too many of certain white blood cells. The antibody Rituximab/Ruxience binds to a protein in cancerous white blood cells and is often used to treat HCL. Researchers want to see if combining it with the drug Moxetumomab pasudotox-tdfk (also called Lumoxiti) can fight HCL better. Objective: To test the safety of Moxetumomab pasudotox taken with Rituximab/Ruxience for people with HCL or HCL variant. Eligibility: People age 18 years and older with HCL or HCL variant that has not responded to standard therapy Design: Participants will be screened with: Medical history Physical exam Blood, heart, and urine tests Test of blood oxygen levels Review of bone marrow. This can be from previous test results or a new sample. Scans Exercise test Participants will get the study drugs in up to 8 cycles. A cycle will last about 28 days. The study drugs will be given through a plastic tube in a vein. In the first week of cycle 1, participants will have: 1 visit to get Rituximab or Ruxience for 7.5 hours 3 visits to get Lumoxiti for 30 minutes per infusion In the first week of cycles 2-8, participants will have: 1. visit to get Rituximab/Ruxience for 2-4 hours and Lumoxiti for 30 minutes 2. visits to get Lumoxiti for 30 minutes per infusion Participants will be asked to drink lots of water and take aspirin during the cycles. They will get drugs to minimize allergic reactions. Participants will repeat screening tests at visits throughout the cycles and 1 follow-up visit. They may have an eye exam. ...

Research Team

Robert J Kreitman, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

Adults over 18 with Hairy Cell Leukemia (HCL) or its variant, who haven't responded to standard therapy. They must have certain blood count levels, be Pseudomonas-immunotoxin naive, and have adequate organ function. Participants should not be pregnant or breastfeeding and must use effective contraception. Those with a history of certain medical conditions like heart disease are excluded.

Inclusion Criteria

Total bilirubin less than or equal to 1.5 mg/dL, unless consistent with Gilbert s (ratio between total and direct bilirubin > 5)

Patients must be Pseudomonas-immunotoxin naive.

Ability of subject to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

I have Hepatitis B but am under treatment and my viral load is low.

Patients with corrected QT interval (Frederica) elevation > 500 msec (manually over-read by medically qualified person) based on at least two separate 12-lead ECGs.

I have a history of blood clots and a genetic condition that makes my blood clot more easily.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Multiple visits for medical history, physical exam, and tests

Treatment

Participants receive Moxetumomab pasudotox-tdfk and Rituximab/Ruxience in up to 8 cycles, each lasting about 28 days

Up to 32 weeks

1 visit for Rituximab/Ruxience and 3 visits for Lumoxiti in the first week of each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 follow-up visit

Long-term follow-up

Participants are monitored for long-term safety and response durability

Approximately 11 months

Treatment Details

Interventions

• Moxetumomab Pasudotox-tdfk
• Rituximab
• Ruxience

Trial Overview The trial is testing the safety of combining Moxetumomab pasudotox-tdfk (Lumoxiti) with Rituximab/Ruxience in patients with relapsed HCL. The treatment involves up to eight cycles of these drugs administered intravenously, along with medications to prevent allergic reactions and instructions for hydration and aspirin intake.

Participant Groups

Group I: Moxetumomab - Dose Expansion 40 mcg/kg Experimental Treatment 7 Interventions

Arm 1 and Arm 2 Moxetumomab Pasudotox-tdfk + Ruxience

Group II: Moxetumomab - Dose Escalation 30 mcg/kg Experimental Treatment 7 Interventions

Arm 1 Moxetumomab Pasudotox-tdfk + Rituximab

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Moxetumomab pasudotox is a new and promising treatment for patients with relapsed/refractory hairy cell leukemia, but there is limited practical guidance on its administration.

Effective nursing care during treatment includes monitoring for side effects, managing hydration, and being vigilant for serious adverse reactions, ensuring patient safety throughout the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moxetumomab Pasudotox: Clinical Experience in Relapsed/Refractory Hairy Cell Leukemia. Feurtado, J., Kreitman, RJ.[2021]

Moxetumomab pasudotox (Lumoxiti®) is an effective treatment for adults with relapsed or refractory hairy cell leukaemia, achieving a durable complete response in about one-third of patients in a pivotal phase III trial.

The treatment has a manageable safety profile, with common side effects like nausea and headache, and serious adverse events such as haemolytic uraemic syndrome are generally reversible with proper monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moxetumomab Pasudotox in Hairy Cell Leukaemia: A Profile of Its Use. Kang, C.[2021]

Moxetumomab pasudotox is an FDA-approved treatment for relapsed or refractory hairy cell leukemia, based on a pivotal phase III study demonstrating its efficacy in this rare cancer.

The treatment targets the CD22 protein on B-cells, and while it can lead to durable remission, practitioners should be aware of common adverse effects and management strategies as its use becomes more widespread.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moxetumomab pasudotox: A first-in-class treatment for hairy cell leukemia. Fancher, KM., Lally-Montgomery, ZC.[2019]

In a study of 40 patients with low-grade or follicular B-cell non-Hodgkin's lymphoma, the combination of Rituxan (Rituximab) and CHOP chemotherapy resulted in a high overall response rate of 95%, with 55% achieving complete remission.

The combination therapy showed promising safety, with common side effects being manageable, and it also indicated potential for clearing minimal residual disease, as evidenced by the conversion of the bcl-2 translocation from positive to negative in several patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. Czuczman, MS., Grillo-López, AJ., White, CA., et al.[2022]

In a review of 49,927 reports from the Spanish Pharmacovigilance System, rituximab was associated with common adverse reactions such as white cell disorders, hypotension, dyspnoea, and pneumonitis, with white cell disorders typically developing around 21 days after treatment.

Trastuzumab was primarily linked to cardiac failure, with many cases occurring alongside other medications, reinforcing the known safety profiles of both drugs as consistent with findings from large clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-marketing safety of antineoplasic monoclonal antibodies: rituximab and trastuzumab. González, V., Salgueiro, E., Jimeno, FJ., et al.[2015]

A meta-analysis of 18 randomized controlled trials involving 11,234 patients found that adding cetuximab to chemotherapy or chemoradiotherapy increases the risk of severe hematologic toxicity events (HTEs), particularly in colorectal cancer and nonsmall cell lung cancer (NSCLC).

Specifically, cetuximab was linked to a higher incidence of grade 3 leucopenia/neutropenia and anemia in colorectal cancer patients, with relative risks of 1.16 and 2.67, respectively, indicating that certain patient groups, like those with K-ras wild type, may be more susceptible to these adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematologic toxicity assessment in solid tumor patients treated with cetuximab: a pooled analysis of 18 randomized controlled trials. Cui, R., Chu, L., Liu, ZQ., et al.[2016]

A phase 3 study involving 407 treatment-naïve patients with diffuse large B-cell lymphoma demonstrated that HLX01, a biosimilar to rituximab, has comparable efficacy to the reference drug, with overall response rates of 94.1% for HLX01 and 92.8% for rituximab, falling within the pre-defined equivalence margin.

The safety profiles of HLX01 and rituximab were similar, with nearly identical rates of treatment-emergent adverse events (99.5% vs. 99.0%) and serious adverse events (34.0% vs. 32.5%), confirming that HLX01 is a safe alternative to rituximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 3 study of rituximab biosimilar HLX01 in patients with diffuse large B-cell lymphoma. Shi, Y., Song, Y., Qin, Y., et al.[2021]

In a pooled analysis of 150 patients with HIV-associated aggressive B-cell non-Hodgkin lymphoma, those treated with R-EPOCH showed significantly better event-free survival (EFS) and overall survival (OS) compared to those receiving R-CHOP, particularly in patients with a CD4 count ≥100/μL.

Patients with CD4 counts <50/μL experienced a much higher rate of treatment-related deaths (37% vs 6%), indicating that lower immune function increases the risk of lethal toxicity during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pooled analysis of AIDS malignancy consortium trials evaluating rituximab plus CHOP or infusional EPOCH chemotherapy in HIV-associated non-Hodgkin lymphoma. Barta, SK., Lee, JY., Kaplan, LD., et al.[2022]

References

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

Moxetumomab Pasudotox: Clinical Experience in Relapsed/Refractory Hairy Cell Leukemia. [2021]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Moxetumomab Pasudotox in Hairy Cell Leukaemia: A Profile of Its Use. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Moxetumomab pasudotox: A first-in-class treatment for hairy cell leukemia. [2019]

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

Hairy Cell Leukemia Treatment Approved. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Moxetumomab pasudotox for the treatment of relapsed and/or refractory hairy cell leukemia. [2020]

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

Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. [2022]

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

Post-marketing safety of antineoplasic monoclonal antibodies: rituximab and trastuzumab. [2015]

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

Hematologic toxicity assessment in solid tumor patients treated with cetuximab: a pooled analysis of 18 randomized controlled trials. [2016]

9. England pubmed.ncbi.nlm.nih.gov

A phase 3 study of rituximab biosimilar HLX01 in patients with diffuse large B-cell lymphoma. [2021]

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

Pooled analysis of AIDS malignancy consortium trials evaluating rituximab plus CHOP or infusional EPOCH chemotherapy in HIV-associated non-Hodgkin lymphoma. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Development of Recombinant Immunotoxins for Hairy Cell Leukemia. [2021]