AVM0703 for Lymphoma

(OPAL Trial)

Recruiting at 12 trial locations

Overseen by Salil Goorha

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: AVM Biotechnology Inc

Must not be taking: Antidepressants

Disqualifiers: Cardiovascular disease, Diabetes, Infections, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This is an open-label, Phase 1/2 study designed to characterize the safety, tolerability, Pharmacokinetics(PK), and preliminary antitumor activity of AVM0703 administered as a single intravenous (IV) infusion to patients with lymphoid malignancies.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that patients with certain conditions like uncontrolled diabetes or significant cardiovascular disease are excluded, which might imply some medication adjustments. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug AVM0703 for treating lymphoma?

Research shows that dexamethasone, a component of AVM0703, has been effective in reducing the size of lymphoma tumors, as seen in cases of adrenal and brain lymphoma. Additionally, dexamethasone has been part of successful treatment regimens for relapsed or refractory lymphoma, indicating its potential effectiveness in similar conditions. ^{1 2 3 4 5}

Is AVM0703 (Dexamethasone) generally safe for humans?

Dexamethasone, also known as AVM0703, has been used in various treatments and is generally considered safe, but it can cause side effects like insomnia and neurobehavioral issues. It has been effective in reducing nausea from chemotherapy and treating lymphoma, but high doses may lead to increased risk of certain relapses in leukemia patients. ^{3 6 7 8 9}

How is the drug AVM0703 (Dexamethasone sodium phosphate) unique for treating lymphoma?

AVM0703, which is a form of dexamethasone, is unique because it can cause rapid and significant reduction in lymphoma size after just a single dose, as demonstrated in a case of adrenal lymphoma. ^{3 5 10 11 12}

Research Team

Elizabeth Budde, MD

Principal Investigator

City of Hope Medical Center

Gary Schiller, MD

Principal Investigator

University of California, Los Angeles

Don Stevens, MD

Principal Investigator

Norton Cancer Institute

Lasika Seneviratne

Principal Investigator

Los Angeles Cancer Network

Pamela Miel, MD

Principal Investigator

Innovative Clinical Research Institute

Nashat Gabrail, M.D.

Principal Investigator

Gabrail Cancer Center Research

Paul Rubinstein, MD

Principal Investigator

University of Illinois at Chicago

Salil Goorha

Principal Investigator

Memphis Baptist Cancer Center

Tamra Slone, MD

Principal Investigator

U Texas SouthWestern

Stefano Tarantolo, MD

Principal Investigator

Nebraska Cancer Specialists

Daniel Kerr

Principal Investigator

ASCLEPES Research Centers

Eligibility Criteria

This trial is for people aged 12 and older, weighing more than 40 kg, with certain types of lymphoid malignancies that have not responded to previous treatments or who cannot receive them due to various reasons. Participants need a minimum level of physical health and organ function, must not be pregnant or breastfeeding, and agree to use contraception.

Inclusion Criteria

My condition did not improve or worsened after previous treatments.

My lymphoma or leukemia has not improved after several treatments.

I can do most activities but may need help.

Exclusion Criteria

I have not had a live vaccine in the last 8 weeks.

Uncontrolled bipolar disorder or schizophrenia

I have had cancer before, but it was either skin cancer treated successfully, a non-spreading bladder cancer, a localized cancer that didn't spread, or any cancer that has been in remission for 2 years or more.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AVM0703 as a single intravenous infusion with repeat dosing every 21 days until intolerance, unacceptable toxicity, or disease progression

Variable, based on patient response

Visits every 21 days for infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment, with survival follow-up at 3, 6, and 12 months post-infusion, and yearly thereafter

12 months

Follow-up visits at 3, 6, and 12 months

Open-label extension (optional)

Participants may be retreated upon disease relapse at a dose previously shown to be safe

Long-term

Treatment Details

Interventions

• AVM0703 (Other)
• Supra-Pharmacologic Dexamethasone sodium phosphate (Corticosteroid)

Trial Overview The OPAL Study is testing AVM0703 as a single IV infusion for patients with lymphoid malignancies. It's an open-label study which means everyone knows what treatment they're getting. The focus is on safety, how the body processes the drug (pharmacokinetics), tolerability, and initial effectiveness against tumors.

Participant Groups

Group I: Primary Mediastinal Large B-cell lymphoma Experimental Treatment 1 Intervention

Primary mediastinal large B-cell lymphoma

Group II: MCL (Chronic Lymphoid Leukemia) Experimental Treatment 1 Intervention

Chronic Lymphoid Leukemia

Group III: DLBCL and high-grade B-cell lymphoma Experimental Treatment 1 Intervention

Diffuse Large Cell B-Lymphoma High-grade B-cell Lymphoma

Group IV: CLL/SLL Experimental Treatment 1 Intervention

Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma

Group V: Burkitt or Burkitt-like lymphoma/leukemia Experimental Treatment 1 Intervention

Burkitt or Burkitt-like lymphoma/leukemia

Group VI: B- or T-ALL Experimental Treatment 1 Intervention

B-lymphoblastic leukemia/lymphoma, T-lymphoblastic leukemia/lymphoma, acute leukemia/lymphoma, acute leukemias of ambiguous lineage, or natural killer (NK) cell lymphoblastic leukemia/lymphoma

Who Is Running the Clinical Trial?

AVM Biotechnology Inc

Lead Sponsor

Trials

3

Recruited

160+

AVM Biotechnology LLC

Lead Sponsor

Trials

2

Recruited

160+

Medpace, Inc.

Industry Sponsor

Trials

98

Recruited

30,400+

Dr. August J. Troendle

Medpace, Inc.

Chief Executive Officer since 1992

MD from the University of Maryland, School of Medicine; MBA from Boston University

Dr. Reinilde Heyrman

Medpace, Inc.

Chief Medical Officer since 2017

MD

Findings from Research

In a study of 28 adults with malignant lymphoma, treatment with desamethasone led to a partial remission in 13 patients, indicating its potential efficacy in certain cases of lymphoma.

Patients who responded to glucocorticoid treatment had more glucocorticoid receptors on their lymphoma cells and showed greater sensitivity to glucocorticoids in laboratory tests, suggesting that receptor levels could help identify which patients might benefit from glucocorticoid therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In-vitro glucocorticoid studies for predicting response to glucocorticoid therapy in adults with malignant lymphoma. Bloomfield, CD., Smith, KA., Peterson, BA., et al.[2019]

In a study of 30 patients with refractory or relapsing non-Hodgkin's lymphoma, the DVIP treatment led to a 33% complete response rate and a 30% partial response rate, with responses lasting from 2.5 to over 24 months.

While DVIP treatment caused significant myelosuppression, it was considered safe as there were no drug-related deaths, indicating it is an effective salvage therapy for aggressive forms of NHL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salvage therapy for non-Hodgkin's lymphoma with a combination of dexamethasone, etoposide, ifosfamide, and cisplatin. Haim, N., Rosenblatt, E., Wollner, M., et al.[2019]

A single low dose of dexamethasone led to a significant reduction in the size of bilateral adrenal lymphoma in a 52-year-old man, highlighting the rapid efficacy of this treatment.

The case suggests that a diagnosis of lymphoma should be considered when adrenal lesions shrink after dexamethasone administration, indicating its potential as a diagnostic tool in such cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Vanishing Adrenal Glands: A Transient Regression of Adrenal Lymphoma After a Single Dose of 1 mg Dexamethasone. Zaman, S., Boharoon, H., Khalid, N., et al.[2022]

In a study of 70 patients with relapsed or refractory lymphomas, the combination of dexamethasone, high-dose cytarabine, and oxaliplatin showed a high overall response rate of 73%, with 43% achieving complete remission.

The treatment was well-tolerated, with no severe nonhematological toxicities reported, and resulted in a 2-year overall survival rate of 71%, indicating it is a safe and effective salvage therapy option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxaliplatin-based chemotherapy (dexamethasone, high-dose cytarabine, and oxaliplatin)±rituximab is an effective salvage regimen in patients with relapsed or refractory lymphoma. Rigacci, L., Fabbri, A., Puccini, B., et al.[2018]

A 54-year-old woman with primary malignant lymphoma in the brain showed significant improvement after receiving dexamethasone, a corticosteroid, which was administered intravenously at a dosage of 8 mg daily.

CT scans taken 10 days after treatment showed dramatic regression of the lymphoma, correlating with the patient's clinical remission, highlighting the potential effectiveness of corticosteroids in managing brain lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Steroid-induced regression of primary malignant lymphoma of the brain. Kikuchi, K., Watanabe, K., Miura, S., et al.[2019]

In a phase II study involving 15 patients with non-Hodgkin's lymphoma (NHL) who had previously failed chemotherapy, the DHAOx regimen (dexamethasone, high-dose ara-C, and oxaliplatin) resulted in a 53% complete response rate, indicating its potential efficacy as a salvage treatment.

DHAOx demonstrated a favorable safety profile, with no increase in serum creatinine levels, suggesting low renal toxicity, and manageable side effects like myelosuppression and transient sensory peripheral neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexamethasone, high-dose cytarabine, and oxaliplatin (DHAOx) as salvage treatment for patients with initially refractory or relapsed non-Hodgkin's lymphoma. Machover, D., Delmas-Marsalet, B., Misra, SC., et al.[2020]

In a trial involving 117 low-risk acute lymphoblastic leukemia patients, reducing the total dose of dexamethasone from 1144 mg/m to 618 mg/m resulted in a significant increase in the 5-year cumulative incidence of isolated central nervous system relapse from 0% to 9.1%.

The study suggests that while lowering dexamethasone aims to decrease life-threatening infections, it may inadvertently increase the risk of cancer relapse in the central nervous system, highlighting a critical balance in treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isolated Central Nervous System Relapse Following Treatment Reduction in Low-risk Acute Lymphoblastic Leukemia at the Children's Cancer Center of Lebanon. El-Khoury, H., Chahrour, M., Ghanem, KM., et al.[2021]

In a study involving 22 women undergoing chemotherapy for breast cancer, high-dose dexamethasone (10 mg) significantly reduced gastrointestinal side effects, with 83% of participants experiencing no GI intolerance compared to 57% in the placebo group.

Dexamethasone not only alleviated nausea and vomiting but also improved energy levels and mood in some participants, indicating its potential benefits beyond just preventing emesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiemetic efficacy of dexamethasone therapy in patients receiving cancer chemotherapy. Cassileth, PA., Lusk, EJ., Torri, S., et al.[2013]

Dexamethasone, while effective for treating pediatric acute lymphoblastic leukemia (ALL), can cause significant neurobehavioral side effects that negatively impact health-related quality of life (HRQoL) in patients, as identified through the Strengths and Difficulties Questionnaire (SDQ).

The current study aims to replicate previous findings that adding physiological hydrocortisone during dexamethasone treatment may alleviate these neurobehavioral issues, with a randomized controlled trial design to assess changes in SDQ scores and other quality of life measures in affected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study protocol: DexaDays-2, hydrocortisone for treatment of dexamethasone-induced neurobehavioral side effects in pediatric leukemia patients: a double-blind placebo controlled randomized intervention study with cross-over design. van Hulst, AM., Verwaaijen, EJ., Fiocco, MF., et al.[2021]

This case report describes the successful treatment of secondary Plasma Cell Leukemia using pomalidomide combined with low-dose dexamethasone, marking a novel approach in this context.

After four treatment cycles, the patient showed significant improvements, including reduced circulating plasma cells and normalization of blood values, with manageable side effects and a response time of 4 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response to pomalidomide plus fixed low-dose dexamethasone in a case of secondary plasma cell leukaemia. Mele, G., Coppi, MR., Guaragna, G., et al.[2016]

In a study of 34 lenalidomide-refractory multiple myeloma patients, the combination of pomalidomide and dexamethasone showed a 47% overall response rate, with some patients achieving very good partial responses and partial responses.

The treatment was well tolerated, although 53% of patients experienced significant hematologic toxicity, including anemia and neutropenia, indicating that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide (CC4047) plus low dose dexamethasone (Pom/dex) is active and well tolerated in lenalidomide refractory multiple myeloma (MM). Lacy, MQ., Hayman, SR., Gertz, MA., et al.[2022]

Pomalidomide, combined with weekly dexamethasone, shows promising efficacy in patients with multiple myeloma who have not responded to lenalidomide and bortezomib, achieving an overall response rate of 49% at 2 mg and 43% at 4 mg daily.

The treatment demonstrated a 6-month overall survival rate of 78% for the 2 mg cohort and 67% for the 4 mg cohort, with myelosuppression being the most common side effect, indicating that while effective, careful monitoring for toxicity is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide plus low-dose dexamethasone in myeloma refractory to both bortezomib and lenalidomide: comparison of 2 dosing strategies in dual-refractory disease. Lacy, MQ., Allred, JB., Gertz, MA., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

In-vitro glucocorticoid studies for predicting response to glucocorticoid therapy in adults with malignant lymphoma. [2019]

2. Germany pubmed.ncbi.nlm.nih.gov

Salvage therapy for non-Hodgkin's lymphoma with a combination of dexamethasone, etoposide, ifosfamide, and cisplatin. [2019]

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

The Vanishing Adrenal Glands: A Transient Regression of Adrenal Lymphoma After a Single Dose of 1 mg Dexamethasone. [2022]

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

Oxaliplatin-based chemotherapy (dexamethasone, high-dose cytarabine, and oxaliplatin)±rituximab is an effective salvage regimen in patients with relapsed or refractory lymphoma. [2018]

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

Steroid-induced regression of primary malignant lymphoma of the brain. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Dexamethasone, high-dose cytarabine, and oxaliplatin (DHAOx) as salvage treatment for patients with initially refractory or relapsed non-Hodgkin's lymphoma. [2020]

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

Isolated Central Nervous System Relapse Following Treatment Reduction in Low-risk Acute Lymphoblastic Leukemia at the Children's Cancer Center of Lebanon. [2021]

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

Antiemetic efficacy of dexamethasone therapy in patients receiving cancer chemotherapy. [2013]

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

Study protocol: DexaDays-2, hydrocortisone for treatment of dexamethasone-induced neurobehavioral side effects in pediatric leukemia patients: a double-blind placebo controlled randomized intervention study with cross-over design. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Response to pomalidomide plus fixed low-dose dexamethasone in a case of secondary plasma cell leukaemia. [2016]

11. England pubmed.ncbi.nlm.nih.gov

Pomalidomide (CC4047) plus low dose dexamethasone (Pom/dex) is active and well tolerated in lenalidomide refractory multiple myeloma (MM). [2022]

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

Pomalidomide plus low-dose dexamethasone in myeloma refractory to both bortezomib and lenalidomide: comparison of 2 dosing strategies in dual-refractory disease. [2021]