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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining Moxetumomab pasudotox-tdfk (Lumoxiti) and Rituximab/Ruxience is effective and safe for treating hairy cell leukemia (HCL), a rare blood cancer. Researchers are investigating whether this combination can better target cancerous white blood cells than current treatments. Individuals with HCL or a variant unresponsive to standard treatments might be suitable for this trial. Participants will receive the treatment in cycles and undergo regular health checks to monitor safety and effectiveness. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

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.

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

Research has shown that Moxetumomab pasudotox-tdfk, also known as Lumoxiti, is approved by the FDA for adults with hairy cell leukemia (HCL) who have tried at least two other treatments. This approval indicates it has been tested for safety in people. In these studies, the treatment was generally well-tolerated, although some people experienced side effects.

Rituximab, another treatment often used for HCL, has also been shown in studies to be generally well-tolerated. Common side effects include fever, chills, and weakness, but these are usually manageable.

In this trial, both Moxetumomab and Rituximab have proven safety records from previous studies and use. Participants can expect regular check-ups to manage any side effects that might occur. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for Hairy Cell Leukemia, like chemotherapy or the monoclonal antibody Rituximab, work by broadly suppressing the immune system or specifically targeting CD20 on B-cells. But Moxetumomab Pasudotox-tdfk is different because it targets CD22, a molecule found on the surface of cancerous B-cells. This unique mechanism allows it to deliver a toxin directly into the cancer cells, potentially reducing side effects and increasing effectiveness. Researchers are excited about the combination with Rituximab or its biosimilar, Ruxience, as these combinations may enhance the treatment's efficacy by using complementary mechanisms to attack the cancer more comprehensively.

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

Research shows that Rituximab/Ruxience can help treat hairy cell leukemia (HCL) by attaching to a protein on cancer cells, enabling the immune system to destroy them. In this trial, participants will receive Moxetumomab pasudotox-tdfk, also known as Lumoxiti, which is approved for patients whose HCL has returned after other treatments. It targets a different protein on the cancer cells, called CD22, and delivers a toxin to kill the cells. By combining these two drugs in the trial, researchers aim to attack the cancer cells in different ways, potentially improving treatment results. Early research on this combination appears promising, but more studies are needed to fully understand its effectiveness. ^{1 6 7 8 9}

Who Is on the Research Team?

Robert J Kreitman, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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 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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03805932?cond=%22Hairy%20Cell%20Leukemia%22&intr=%22analgesics,%20non-narcotic%22&viewType=Table&rank=1&tab=results

Study Results | Moxetumomab Pasudotox-tdfk (Lumoxiti ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

2. clinicalstudies.info.nih.gov clinicalstudies.info.nih.gov/protocoldetails.aspx?id=19-C-0042&&query=a

Protocol Details A Phase I Study of Moxetumomab Pasudotox-tdfk (Lumoxiti (TM)) and either Rituximab (Rituxan (R)) or Ruxience for Relapsed Hairy Cell Leukemia. This study is ...

3. cancer.gov cancer.gov/clinicaltrials/NCI-2019-00464

Moxetumomab Pasudotox-tdfk (Lumoxiti(TM)) and Either ... 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 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03805932

NCT03805932 | Moxetumomab Pasudotox-tdfk (Lumoxiti ... 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.

5. jhoponline.com jhoponline.com/2019-fourth-annual-oncology-guide-to-new-fda-approvals/lumoxiti-moxetumomab-pasudotox-tdfk-first-cd22-directed-cytotoxin-fda-approved-for-relapsed-or-refractory-hairy-cell-leukemia

Lumoxiti (Moxetumomab Pasudotox-tdfk) First CD22 ... “Lumoxiti fills an unmet need for patients with hairy cell leukemia whose disease has progressed after trying other FDA-approved therapies,” said Richard Pazdur ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2019.37.15_suppl.7014

Pooled safety summary for patients treated with the CD22- ... Background: Moxetumomab pasudotox-tdfk was FDA-approved in 2018 for the treatment of adults with relapsed/refractory hairy cell leukemia (HCL) ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6964124/

Contextualizing the Use of Moxetumomab Pasudotox in the ... In September 2018, the U.S. Food and Drug Administration approved Moxe for the treatment of relapsed/refractory HCL after ≥2 prior therapies. Moxe is undergoing ...

8. cancernetwork.com cancernetwork.com/view/hairy-cell-leukemia-drug-moxetumomab-pasudotox-tdfk-to-be-withdrawn-in-the-united-states-market

Hairy Cell Leukemia Drug Moxetumomab Pasudotox-tdfk ... The FDA approved moxetumomab pasudotox for patients with relapsed/refractory hairy cell leukemia who had received at least 2 prior systemic ...

9. ahdbonline.com ahdbonline.com/issues/2019/march-2019-vol-12-tenth-annual-payers-guide/lumoxiti-moxetumomab-pasudotox-tdfk-first-cd22-directed-cytotoxin-approved-for-relapsed-or-refractory-hairy-cell-leukemia

Lumoxiti (Moxetumomab Pasudotox-tdfk) First CD22 ... “Lumoxiti fills an unmet need for patients with hairy cell leukemia whose disease has progressed after trying other FDA-approved therapies,” said Richard Pazdur ...