Belantamab Mafodotin for AL Amyloidosis

Recruiting at 4 trial locations

Overseen By Donglan Xia

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: University of Texas Southwestern Medical Center

Must be taking: Proteosome inhibitors, Alkylators, CD38 antibodies

Disqualifiers: Multiple myeloma, Corneal disease, Cardiovascular conditions, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing Belantamab mafodotin, a drug that targets and kills harmful cells, on patients with Relapsed Refractory AL Amyloidosis who have not responded to other treatments. The drug works by attaching to bad cells and delivering a toxic substance to eliminate them. Belantamab mafodotin is a newly approved treatment for certain types of cancer.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that patients must have completed other systemic therapy or investigational drugs more than 28 days before registration, which might imply a need to pause certain treatments. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Belantamab Mafodotin for AL Amyloidosis?

Belantamab, an anti-BCMA monoclonal antibody, is being investigated for AL amyloidosis, and similar drugs like daratumumab have shown promising results in treating this condition. Advances in AL amyloidosis treatment suggest that targeting specific proteins involved in the disease, like BCMA, could be effective. ^{1 2 3 4 5}

What makes the drug Belantamab Mafodotin unique for treating AL Amyloidosis?

Belantamab Mafodotin is unique because it targets BCMA (B-cell maturation antigen), which is a protein found on the surface of certain cells, including those involved in AL Amyloidosis. This targeted approach is different from traditional chemotherapy, which affects both healthy and diseased cells. ^{6 7 8 9 10}

Research Team

Larry Anderson, M.D.

Principal Investigator

UT Southwestern Medical Center

Eligibility Criteria

Adults over 18 with relapsed or refractory AL Amyloidosis, who have tried multiple treatments including a proteasome inhibitor and stem cell transplant. They must have an ejection fraction >35%, stable heart condition, measurable disease, and adequate organ function. Women of childbearing potential need a negative pregnancy test; men agree to contraception rules. Excludes those with recent major surgery, active infections, unstable health conditions, or hypersensitivity to the drug.

Inclusion Criteria

I cannot tolerate or did not respond to previous treatments.

I am a woman who can have children and have a negative pregnancy test taken within the last 3 days.

My AL Amyloidosis affects one or more of my organs.

Exclusion Criteria

My liver and bile ducts are currently stable.

I have a serious heart condition.

Presence of any comorbid or uncontrolled medical condition at screening, which in the opinion of the investigator would increase the potential risk to the subject

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Exploration (Escalation)

This phase will identify and select an appropriate dose of Belantamab mafodotin regarding safety and preliminary evaluation of hematological and organ response.

Up to 18 weeks

Visits every 8-12 weeks depending on dose cohort

Dose Cohort Expansion

This phase will further define the depth and durability of both hematological and organ response at the dose level found to be safe and effective in phase 1.

Up to 2 years

Visits every 4-12 weeks as determined by Part 1 recommended dosage

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years after the last dose

Treatment Details

Interventions

• Belantamab mafodotin (Monoclonal Antibodies)

Trial Overview The trial is testing different doses of Belantamab Mafodotin (1.9mg/kg or 2.5mg/kg) given every 4, 6 or 8 weeks for safety and effectiveness in treating AL Amyloidosis that has come back or hasn't responded to treatment.

Participant Groups

Group I: Cohort Dose Expansion for Part 2 Experimental Treatment 1 Intervention

Cohort Dose expansion for Part 2: Belantamab mafodotin Dose from1.0 mg/kg to 2.5mg/kg every 4 weeks, 6 weeks, 8 weeks, or 12 weeks as determined by Part 1 recommended dosage calculations.

Group II: Cohort (DL 0) for Part 1 Experimental Treatment 1 Intervention

Cohort (DL 0) for Starting Dose : 1.9 mg/kg Belantamab mafodotin intravenously every 8 weeks

Group III: Cohort (DL -3) for Part 1 Experimental Treatment 1 Intervention

Cohort (DL -3) for Dose De-escalation: 1.0 mg/kg Belantamab mafodotin intravenously every 12 weeks

Group IV: Cohort (DL -2) for Part 1 Experimental Treatment 2 Interventions

Cohort (DL -2) for Dose De-escalation: 1.4 mg/kg Belantamab mafodotin intravenously every 12 weeks

Group V: Cohort (DL -1) for Part 1 Experimental Treatment 2 Interventions

Cohort (DL -1) for Dose De-escalation : 1.9 mg/kg Belantamab mafodotin intravenously every 12 weeks

Group VI: Cohort (DL +1) for Part 1 Experimental Treatment 1 Intervention

Cohort (DL +1) for Dose Escalation: 2.5 mg/kg Belantamab mafodotin intravenously every 8 weeks

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

GlaxoSmithKline

Industry Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Findings from Research

The combination therapy of daratumumab, cyclophosphamide, bortezomib, and dexamethasone (daratumumab-CyBorD) has become the new standard-of-care for systemic light chain (AL) amyloidosis, showing high rates of hematologic and organ response.

Recent advancements in patient selection and induction regimens have significantly reduced the mortality associated with autologous stem cell transplant (ASCT), while new treatments like venetoclax are proving effective for patients with specific genetic abnormalities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in the treatment of light chain amyloidosis. Palladini, G., Milani, P.[2023]

In a study of 49 patients with relapsed/refractory AL amyloidosis treated with daratumumab, the overall hematologic response rate was 81%, with 64% achieving a very good partial response or better, indicating strong efficacy in this challenging patient population.

Daratumumab was found to be safe and well tolerated, with no patients discontinuing treatment due to toxicity, and it demonstrated significant cardiac and renal responses (74% and 73%, respectively), supporting its use in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab for relapsed AL amyloidosis-When cumulative real-world data precedes clinical trials: A multisite study and systematic literature review. Shragai, T., Gatt, M., Lavie, N., et al.[2021]

AL amyloidosis is a serious condition that can lead to cardiac emergencies, and understanding its pathophysiology is essential for effective treatment, particularly focusing on stabilizing light chains.

Recent advancements in treatment include the approval of daratumumab and ongoing investigations of novel therapies like isatuximab, belantamab, and elotuzumab, which target specific proteins on plasma cells, offering hope for improved management of this complex disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future Developments in Light Chain Amyloidosis Management. Rodriguez, M., Lenihan, D., Merlini, G.[2022]

In a phase II trial involving 31 patients with relapsed/refractory AL amyloidosis, 57% achieved a partial hematologic response or better after treatment with bendamustine and dexamethasone, indicating significant efficacy.

The treatment was well tolerated, with no grade 5 adverse events reported, although 65% of patients experienced grade 3-4 adverse events, primarily myelosuppression, fatigue, and nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine With Dexamethasone in Relapsed/Refractory Systemic Light-Chain Amyloidosis: Results of a Phase II Study. Lentzsch, S., Lagos, GG., Comenzo, RL., et al.[2021]

Gamma-tert-Butylaminopterin (gamma-tBAMT) was synthesized and shown to have similar inhibitory effects on dihydrofolate reductase (DHFR) as gamma-tert-butyl methotrexate (gamma-tBMTX), indicating potential as an effective treatment option.

In vivo studies demonstrated that gamma-tBAMT was nearly as potent as gamma-tBMTX against L1210 leukemia, but gamma-tBAMT was more effective than methotrexate and showed only partial cross-resistance in MTX-resistant cell lines, suggesting it may overcome some resistance mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methotrexate analogues. 25. Chemical and biological studies on the gamma-tert-butyl esters of methotrexate and aminopterin. Rosowsky, A., Freisheim, JH., Bader, H., et al.[2019]

Pemetrexed disodium is a multitargeted antifolate that works by inhibiting key enzymes involved in DNA synthesis, making it effective against various solid tumors, including breast cancer.

When combined with gemcitabine, pemetrexed disodium shows promising clinical activity for treating metastatic breast cancer, indicating its potential as a combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine and Pemetrexed disodium in treating breast cancer. Adjei, AA.[2022]

Chemically self-assembled antibody nanorings (CSANs) can effectively target CD3+ T-leukemia cells, showing rapid internalization and stability for several hours, which allows for monitoring their cellular behavior using fluorescence.

The CSANs demonstrated significantly higher cytotoxicity (GI(50) = 0.5-1.5 μM) compared to the bis-methotrexate ligand alone (GI(50) > 20 μM), indicating their potential as effective tissue-selective drug carriers while remaining nontoxic to the cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemically self-assembled antibody nanostructures as potential drug carriers. Fegan, A., Kumarapperuma, SC., Wagner, CR.[2021]

In a subset analysis of a phase II trial involving 72 heavily pretreated metastatic breast cancer patients, pemetrexed showed a 26% overall response rate, indicating its potential effectiveness after prior treatments with anthracyclines and taxanes.

Pemetrexed was well tolerated, with a median duration of response of 5.4 months and a median survival of 12.8 months, suggesting it could be a viable option for patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of pemetrexed (ALIMTA, multitargeted antifolate, LY231514) in metastatic breast cancer patients previously treated with an anthracycline and a taxane: an interim analysis. Spielmann, M., Martin, M., Namer, M., et al.[2016]

Alimta, a multitargeted antifolate, has shown promising results as a single agent for treating malignant pleural mesothelioma (MPM), a rare and aggressive cancer with no proven standard chemotherapy.

A recent phase III trial demonstrated that combining Alimta with cisplatin significantly improves treatment efficacy compared to cisplatin alone, and vitamin supplementation can help reduce side effects without affecting the drug's effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of Alimta in the treatment of malignant pleural mesothelioma: an overview of preclinical and clinical trials. Hanauske, AR.[2015]

References

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

Advances in the treatment of light chain amyloidosis. [2023]

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

Teclistamab in relapsed or refractory AL amyloidosis, a multinational retrospective case series. [2023]

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

Daratumumab for relapsed AL amyloidosis-When cumulative real-world data precedes clinical trials: A multisite study and systematic literature review. [2021]

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

Future Developments in Light Chain Amyloidosis Management. [2022]

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

Bendamustine With Dexamethasone in Relapsed/Refractory Systemic Light-Chain Amyloidosis: Results of a Phase II Study. [2021]

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

Methotrexate analogues. 25. Chemical and biological studies on the gamma-tert-butyl esters of methotrexate and aminopterin. [2019]

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

Gemcitabine and Pemetrexed disodium in treating breast cancer. [2022]

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

Chemically self-assembled antibody nanostructures as potential drug carriers. [2021]

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

Activity of pemetrexed (ALIMTA, multitargeted antifolate, LY231514) in metastatic breast cancer patients previously treated with an anthracycline and a taxane: an interim analysis. [2016]

10. Ireland pubmed.ncbi.nlm.nih.gov

The role of Alimta in the treatment of malignant pleural mesothelioma: an overview of preclinical and clinical trials. [2015]