Flotetuzumab for CD123-Positive Hematological Malignancies

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: CNS involvement, Autoimmune disorders, others

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

Compensation: Varies

Number of Visits: 3

13 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial studies the best dose and side effects of flotetuzumab for the treatment of patients with blood cancers (hematological malignancies) that have spread to other places in the body (advanced) and have come back after a period of improvement (relapsed) or does not respond to treatment (refractory). Flotetuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, certain treatments like chemotherapy, radiation, and some immunotherapies must be stopped 14 days before starting the trial, and high-dose steroids must be stopped 3 days before. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the drug Flotetuzumab for CD123-positive hematological malignancies?

Research shows that targeting CD123, a marker found on certain cancer cells, can be effective in treating blood cancers. Other treatments targeting CD123, like IMGN632, have shown promise in killing cancer cells in lab studies, suggesting that Flotetuzumab might also be effective. ^{1 2 3 4 5}

What safety data exists for Flotetuzumab or similar treatments in humans?

The research on lintuzumab, a similar treatment, shows it was generally well tolerated in patients with certain blood cancers, with the most common side effect being temporary chills during the first infusion. ^{6 7 8 9 10}

How is the drug Flotetuzumab unique for treating CD123-positive hematological malignancies?

Flotetuzumab is unique because it targets CD123, a protein found on leukemia stem cells, which are often resistant to traditional treatments. This makes it a promising option for patients with certain blood cancers that overexpress CD123, offering a more targeted approach compared to conventional therapies. ^{1 2 3 5 11}

Research Team

Ibrahim Aldoss, MD

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for adults with advanced blood cancers expressing CD123 who have not responded to standard treatments or whose disease has returned. Eligible participants must meet specific health criteria, including organ function and blood counts, and agree to use effective birth control. Those with recent transplants, untreated autoimmune disorders, active infections, or certain other medical conditions are excluded.

Inclusion Criteria

Platelets >= 75,000/ul (without bone marrow involvement, performed within 14 days prior to day 1 of protocol therapy)

My Hodgkin lymphoma did not respond to PD-1/PD-L1 inhibitors or brentuximab vedotin.

My hairy cell leukemia didn't respond to or got worse after purine analog treatment.

Exclusion Criteria

I have had or been checked for brain involvement but am currently free of it.

I haven't had most cancer treatments in the last 2 weeks but some medications are exceptions.

I have not had major surgery or serious injury in the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Therapy

Patients receive flotetuzumab via continuous IV infusion on days 1-28. Additional cycles may be given based on response.

4-24 weeks

Continuous IV infusion

Consolidation Therapy

Patients who achieve certain responses receive flotetuzumab via continuous IV infusion on days 1-28 for up to 5 or 6 cycles.

4-24 weeks

Continuous IV infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Every 3 months

Treatment Details

Interventions

• Flotetuzumab

Trial Overview The trial is testing the optimal dose and side effects of flotetuzumab in patients with various hematological malignancies that express CD123. Flotetuzumab is a monoclonal antibody designed to inhibit cancer cell growth. The study includes supportive medications like acetaminophen and dexamethasone to manage potential reactions.

Participant Groups

Group I: Treatment (flotetuzumab) Experimental Treatment 6 Interventions

INDUCTION THERAPY: Patients receive flotetuzumab via continuous IV infusion on days 1-28. Patients who achieve SD/PR (Cohort A) or PR/CI (Cohort B), receive an additional induction cycle. Patients who achieve PR (Cohort A) or PR/CI/MMR (Cohort B) after cycle 2 re-induction, may continue induction therapy for up to 4 more cycles. CONSOLIDATION THERAPY: Patients who achieve CR/CRi/CRh/MLFS (Cohort A) or CR/MR (Cohort B) after cycle 1 or cycle 2 of induction therapy, receive flotetuzumab via continuous IV infusion on days 1-28 for up to 5 and 6 cycles, respectively, in the absence of disease progression or unacceptable toxicity. Patients with PR (Cohort A) or PR/CI/MMR (Cohort B) who have received up to 6 cycles of induction therapy may receive up to 2 cycles of consolidation therapy in the absence of disease progression or unacceptable toxicity.

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+

Findings from Research

CD123 is highly expressed in B acute lymphoblastic leukemia/lymphoma, with 89.6% of patients showing expression, making it a potential target for therapies like IMGN632.

IMGN632, a CD123-targeted antibody-drug conjugate, showed strong cytotoxic effects in vitro, eliminating over 90% of B acute lymphoblastic leukemia/lymphoma blasts at low concentrations while sparing normal lymphocytes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD123 expression patterns and selective targeting with a CD123-targeted antibody-drug conjugate (IMGN632) in acute lymphoblastic leukemia. Angelova, E., Audette, C., Kovtun, Y., et al.[2020]

Targeting the interleukin 3 receptor α chain (CD123) on leukemia stem cells has been explored as a treatment for various myeloid malignancies, but the success of these therapies has been limited, indicating a need for better patient selection criteria.

Understanding the patterns of CD123 expression and its biological significance is essential for improving the effectiveness of CD123-targeting therapies in hematologic malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting CD123 in hematologic malignancies: identifying suitable patients for targeted therapy. Patnaik, MM., Mughal, TI., Brooks, C., et al.[2021]

CD123, a receptor highly expressed in leukemic stem cells (LSCs) but not in normal stem cells, is a promising target for therapies aimed at treating refractory or relapsed leukemia, as it is linked to treatment response and prognosis.

Recent advancements in anti-CD123 therapies, including neutralizing antibodies and CAR-T cell therapies, show potential in effectively targeting LSCs, which could improve outcomes for patients with leukemia who do not respond to traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD123: A Novel Biomarker for Diagnosis and Treatment of Leukemia. Shi, M., Su, RJ., Parmar, KP., et al.[2020]

Pertuzumab is an effective treatment for metastatic HER2-positive breast cancer, especially when combined with trastuzumab and docetaxel, showing significant improvements in progression-free and overall survival in treatment-naive patients.

As a HER dimerization inhibitor, pertuzumab works differently than trastuzumab, allowing for a more complete blockade of HER2 signaling, and has a tolerable safety profile, making it a recommended first-line therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab for the treatment of human epidermal growth factor receptor type 2-positive metastatic breast cancer. Chung, C., Lam, MS.[2019]

In a comprehensive analysis of 65,099 patient-years of tocilizumab (TCZ) exposure, the rates of serious adverse events (SAEs) reported in postmarketing data were found to be similar to those observed in clinical trials and external comparator populations, indicating consistent safety profiles across different settings.

The study highlights that the rates of specific SAEs, such as serious hepatic events and myocardial infarctions, were comparable to those seen in anti-tumor necrosis factor (aTNF) treated rheumatoid arthritis patients, suggesting that TCZ's safety profile is in line with existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab in rheumatoid arthritis: a case study of safety evaluations of a large postmarketing data set from multiple data sources. Curtis, JR., Perez-Gutthann, S., Suissa, S., et al.[2019]

References

1. Italy pubmed.ncbi.nlm.nih.gov

CD123 expression patterns and selective targeting with a CD123-targeted antibody-drug conjugate (IMGN632) in acute lymphoblastic leukemia. [2020]

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

Targeting CD123 in hematologic malignancies: identifying suitable patients for targeted therapy. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

CD123 as a Biomarker in Hematolymphoid Malignancies: Principles of Detection and Targeted Therapies. [2020]

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

Rituximab Improves the Outcome of Patients With Grade 3 Follicular Lymphoma Receiving Anthracycline-Based Therapy. [2018]

5. United Arab Emirates pubmed.ncbi.nlm.nih.gov

CD123: A Novel Biomarker for Diagnosis and Treatment of Leukemia. [2020]

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

Complete remissions observed in acute myeloid leukemia following prolonged exposure to lintuzumab: a phase 1 trial. [2022]

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

Pertuzumab for the treatment of human epidermal growth factor receptor type 2-positive metastatic breast cancer. [2019]

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

Intravenous corticosteroids to reduce gemtuzumab ozogamicin infusion reactions. [2022]

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

Tocilizumab in rheumatoid arthritis: a case study of safety evaluations of a large postmarketing data set from multiple data sources. [2019]

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

Phase I study of the humanized anti-CD40 monoclonal antibody dacetuzumab in refractory or recurrent non-Hodgkin's lymphoma. [2021]

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

Flai (fludarabine, cytarabine, idarubicin) plus low-dose Gemtuzumab Ozogamicin as induction therapy in CD33-positive AML: Final results and long term outcome of a phase II multicenter clinical trial. [2019]