RECRUITING

The OPAL Study: AVM0703 for Treatment of Lymphoid Malignancies

Conditions

Lymphoid Malignancies Diffuse large B-cell lymphoma (DLBCL)B-cell lymphoma Mantle cell lymphoma (MCL)Primary mediastinal large B-cell Lymphoma Primary DLBCL of the central nervous system (CNS)Burkitt or Burkitt-like lymphoma/leukemia Chronic lymphocytic leukemia (CLL)Small lymphocytic leukemia (SLL)B-cell leukemia/lymphoma T-cell leukemia/lymphoma Acute leukemias of ambiguous lineage Natural Killer (NK) cell lymphoblastic leukemia/lymphoma Advanced or Aggressive lymphoma/lymphoproliferative disease Follicular Lymphoma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

An Open Label, Phase 1/2 Study Evaluating Immunomodulatory AVM0703 in Patients With Lymphoid Malignancies (OPAL Study)

Quick Facts

Study Start:2020-11-06

Study Completion:2025-06-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04329728

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:12 Years to 95 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* 1. Age ≥12 years and weight ≥40 kg; 2. Histologically confirmed diagnosis per 2016 World Health Organization (WHO) classification of lymphoid neoplasms160 and per the 2016 WHO classification of acute leukemia161 of the following indications: * DLBCL, including arising from follicular lymphoma; * High-grade B-cell lymphoma; * MCL; * Primary mediastinal large B-cell lymphoma; * Primary DLBCL of the CNS; * Burkitt or Burkitt-like lymphoma/leukemia; * CLL/SLL; or * B-lymphoblastic leukemia/lymphoma, T-lymphoblastic leukemia/lymphoma, acute leukemia/lymphoma, acute leukemias of ambiguous lineage, or NK cell lymphoblastic leukemia/lymphoma; 3. Patients must have relapsed or refractory (R/R) disease with prior therapies defined below: * DLBCL and high-grade B-cell lymphoma: * MCL: * Primary mediastinal large B-cell lymphoma: R/R after ≥1 line of therapy and are not eligible for or have recurred after autologous HCT or CAR T cell therapy, or for whom no standard therapy is available; * Primary DLBCL of the CNS: R/R after ≥1 line of therapy including methotrexate (unless intolerant to methotrexate) and are not eligible for or have recurred after autologous HCT or CAR T cell therapy, or for whom no standard therapy is available; * Burkitt or Burkitt-like lymphoma/leukemia: R/R after ≥1 line of therapy including methotrexate (unless intolerant to methotrexate) and are not eligible for or have recurred after autologous HCT or CAR T cell therapy, or for whom no standard therapy is available; * CLL/SLL: patients who have active disease requiring treatment and who are deemed at high-risk for disease progression by the investigator or have high risk features per the iwCLL criteria, such as primary resistance to first-line chemo(immune)therapy, or progression of disease \<3 years after fludarabine-based chemo(immune)therapy, or leukemia cells with del(17p)/TP53 mutation, must be: * Acute lymphoblastic leukemia (ALL): * B-cell lymphoblastic leukemia/lymphoma: ≥2 lines of therapy including approved CAR T cell therapies, inotuzumab ozogamicin, or blinatumomab, or for whom no standard therapy is available; * T-cell lymphoblastic leukemia/lymphoma: ≥2 lines of therapy including nelarabine, or for whom no standard therapy is available; * NK cell leukemia/lymphoma: ≥1 line of therapy or for whom no standard therapy is available; * All other diagnoses: R/R after autologous or allogeneic HCT; or R/R after at least one line of therapy, or for whom no standard therapy is available. 4. Lansky (12 to 15 years of age) (Appendix G) or Karnofsky (≥16 years of age) (Appendix H) performance status ≥50; 5. Screening laboratory values that meet all of the following criteria: * Absolute neutrophil count ≥0.05 × 109/L; * Platelet count ≥25 × 109/L; * Hemoglobin ≥6.5 g/dL; * • Aspartate aminotransferase or alanine aminotransferase ≥2.5 × ULN, unless due to the disease; * Total bilirubin \<1.5 × ULN (if secondary to Gilbert's syndrome, \<3 × ULN is permitted), unless due to the disease; and * Glomerular filtration rate ≥30 mL/min ; except for patients on metformin at baseline GFR must be ≥45 mL/min; GFR can be calculated by the Cockcroft-Gault formula Appendix C); 6. Minimum level of pulmonary reserve defined as \<Grade 2 dyspnea and pulse oximetry ≥92% on room air; 7. Females of childbearing potential must have a negative serum pregnancy test at screening. Females of childbearing potential and nonsterile males must agree to use medically effective methods of contraception from the time of informed consent/assent through 1 month after study drug infusion, which must, at a minimum, include a barrier method; and 8. The ability to understand and willingness to sign a written informed consent form (ICF) and the ability to adhere to the study schedule and prohibitions. Patients under the age of 18 years (or other age as defined by regional law or regulation) must be willing and able to provide written assent and have a parent(s) or guardian(s) willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to performance of any study-related procedure.	* Patients who meet any of the following criteria will be excluded from participation in the study for Phase 2: 1. History of another malignancy, except for the following: * Adequately treated local basal cell or squamous cell carcinoma of the skin; * Adequately treated carcinoma in situ without evidence of disease; * Adequately treated papillary, noninvasive bladder cancer; or * Other cancer that has been in complete remission for ≥2 years. Patients with low-grade prostate cancer, on active surveillance, and not expected to clinically progress over 2 years are allowed; 2. Significant cardiovascular disease (e.g., myocardial infarction, arterial thromboembolism, cerebrovascular thromboembolism) within 3 months prior to the start of AVM0703 administration, angina requiring therapy, symptomatic peripheral vascular disease, New York Heart Association Class III or IV congestive heart failure, left ventricular ejection fraction \<30%, left ventricular fractional shortening \<20%, or uncontrolled ≥Grade 3 hypertension (diastolic blood pressure \>100 mmHg or systolic blood pressure \>150 mmHg) despite antihypertensive therapy for patients ≥18 years of age, or uncontrolled stage 2 hypertension (diastolic blood pressure \>90 mmHg or systolic blood pressure \>140 mmHg) despite antihypertensive therapy for patients ≥12 years of age; 3. Significant screening electrocardiogram (ECG) abnormalities, including unstable cardiac arrhythmia requiring medication, atrial fibrillation/flutter, second degree atrioventricular (AV) block type 2, third-degree AV block, ≥Grade 2 bradycardia, or heart rate corrected QT interval using Fridericia's formula \>480 msec; 4. Known gastric or duodenal ulcer; 5. Uncontrolled type 1 or type 2 diabetes; 6. Known hypersensitivity or allergy to the study drug or any of its excipients; 7. Untreated ongoing bacterial, fungal, or viral infection (including upper respiratory tract infections) at the start of AVM0703 administration, including the following: * Positive hepatitis B surface antigen and/or hepatitis B core antibody test plus a positive hepatitis B polymerase chain reaction (PCR) assay. Patients with a negative PCR assay are permitted with appropriate antiviral prophylaxis; * Positive hepatitis C virus antibody (HCV Ab) test. Patients with a positive HCV Ab test are eligible if they are negative for hepatitis C virus by PCR; * Positive human immunodeficiency virus (HIV) antibody test with detectable HIV load by PCR, or the patient is not able to tolerate antiretroviral therapy; or * Positive tuberculosis test during screening; test must be positive and not indeterminate due to anergy; if the result is indeterminate due to anergy the patient must not have a history of recent exposure to tuberculosis. Patients in Phase 2 repeat dosing cohorts should not travel to any destination where they might be exposed to tuberculosis during their entire treatment period with AVM0703. 8. Received live vaccination within 8 weeks of screening; 9. Pregnant or breastfeeding; 10. Concurrent participation in another therapeutic clinical study (except AVM0703-001); or 11. Uncontrolled bipolar disorder or schizophrenia. Patients with a diagnosis, past or current, of bipolar disorder or schizophrenia or having a history of severe depression or substance abuse must be prophylactically treated with circadian physiologic hydrocortisone per section 5.5.3.3 CNS prophylaxis, without exception.

Inclusion Criteria

Exclusion Criteria

* 1. Age ≥12 years and weight ≥40 kg;
2. Histologically confirmed diagnosis per 2016 World Health Organization (WHO) classification of lymphoid neoplasms160 and per the 2016 WHO classification of acute leukemia161 of the following indications:
* DLBCL, including arising from follicular lymphoma;
* High-grade B-cell lymphoma;
* MCL;
* Primary mediastinal large B-cell lymphoma;
* Primary DLBCL of the CNS;
* Burkitt or Burkitt-like lymphoma/leukemia;
* CLL/SLL; or
* B-lymphoblastic leukemia/lymphoma, T-lymphoblastic leukemia/lymphoma, acute leukemia/lymphoma, acute leukemias of ambiguous lineage, or NK cell lymphoblastic leukemia/lymphoma;
3. Patients must have relapsed or refractory (R/R) disease with prior therapies defined below:
* DLBCL and high-grade B-cell lymphoma:
* MCL:
* Primary mediastinal large B-cell lymphoma: R/R after ≥1 line of therapy and are not eligible for or have recurred after autologous HCT or CAR T cell therapy, or for whom no standard therapy is available;
* Primary DLBCL of the CNS: R/R after ≥1 line of therapy including methotrexate (unless intolerant to methotrexate) and are not eligible for or have recurred after autologous HCT or CAR T cell therapy, or for whom no standard therapy is available;
* Burkitt or Burkitt-like lymphoma/leukemia: R/R after ≥1 line of therapy including methotrexate (unless intolerant to methotrexate) and are not eligible for or have recurred after autologous HCT or CAR T cell therapy, or for whom no standard therapy is available;
* CLL/SLL: patients who have active disease requiring treatment and who are deemed at high-risk for disease progression by the investigator or have high risk features per the iwCLL criteria, such as primary resistance to first-line chemo(immune)therapy, or progression of disease \<3 years after fludarabine-based chemo(immune)therapy, or leukemia cells with del(17p)/TP53 mutation, must be:
* Acute lymphoblastic leukemia (ALL):
* B-cell lymphoblastic leukemia/lymphoma: ≥2 lines of therapy including approved CAR T cell therapies, inotuzumab ozogamicin, or blinatumomab, or for whom no standard therapy is available;
* T-cell lymphoblastic leukemia/lymphoma: ≥2 lines of therapy including nelarabine, or for whom no standard therapy is available;
* NK cell leukemia/lymphoma: ≥1 line of therapy or for whom no standard therapy is available;
* All other diagnoses: R/R after autologous or allogeneic HCT; or R/R after at least one line of therapy, or for whom no standard therapy is available.
4. Lansky (12 to 15 years of age) (Appendix G) or Karnofsky (≥16 years of age) (Appendix H) performance status ≥50;
5. Screening laboratory values that meet all of the following criteria:
* Absolute neutrophil count ≥0.05 × 109/L;
* Platelet count ≥25 × 109/L;
* Hemoglobin ≥6.5 g/dL;
* • Aspartate aminotransferase or alanine aminotransferase ≥2.5 × ULN, unless due to the disease;
* Total bilirubin \<1.5 × ULN (if secondary to Gilbert's syndrome, \<3 × ULN is permitted), unless due to the disease; and
* Glomerular filtration rate ≥30 mL/min ; except for patients on metformin at baseline GFR must be ≥45 mL/min; GFR can be calculated by the Cockcroft-Gault formula Appendix C);
6. Minimum level of pulmonary reserve defined as \<Grade 2 dyspnea and pulse oximetry ≥92% on room air;
7. Females of childbearing potential must have a negative serum pregnancy test at screening. Females of childbearing potential and nonsterile males must agree to use medically effective methods of contraception from the time of informed consent/assent through 1 month after study drug infusion, which must, at a minimum, include a barrier method; and
8. The ability to understand and willingness to sign a written informed consent form (ICF) and the ability to adhere to the study schedule and prohibitions. Patients under the age of 18 years (or other age as defined by regional law or regulation) must be willing and able to provide written assent and have a parent(s) or guardian(s) willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to performance of any study-related procedure.

* Patients who meet any of the following criteria will be excluded from participation in the study for Phase 2:
1. History of another malignancy, except for the following:
* Adequately treated local basal cell or squamous cell carcinoma of the skin;
* Adequately treated carcinoma in situ without evidence of disease;
* Adequately treated papillary, noninvasive bladder cancer; or
* Other cancer that has been in complete remission for ≥2 years. Patients with low-grade prostate cancer, on active surveillance, and not expected to clinically progress over 2 years are allowed;
2. Significant cardiovascular disease (e.g., myocardial infarction, arterial thromboembolism, cerebrovascular thromboembolism) within 3 months prior to the start of AVM0703 administration, angina requiring therapy, symptomatic peripheral vascular disease, New York Heart Association Class III or IV congestive heart failure, left ventricular ejection fraction \<30%, left ventricular fractional shortening \<20%, or uncontrolled ≥Grade 3 hypertension (diastolic blood pressure \>100 mmHg or systolic blood pressure \>150 mmHg) despite antihypertensive therapy for patients ≥18 years of age, or uncontrolled stage 2 hypertension (diastolic blood pressure \>90 mmHg or systolic blood pressure \>140 mmHg) despite antihypertensive therapy for patients ≥12 years of age;
3. Significant screening electrocardiogram (ECG) abnormalities, including unstable cardiac arrhythmia requiring medication, atrial fibrillation/flutter, second degree atrioventricular (AV) block type 2, third-degree AV block, ≥Grade 2 bradycardia, or heart rate corrected QT interval using Fridericia's formula \>480 msec;
4. Known gastric or duodenal ulcer;
5. Uncontrolled type 1 or type 2 diabetes;
6. Known hypersensitivity or allergy to the study drug or any of its excipients;
7. Untreated ongoing bacterial, fungal, or viral infection (including upper respiratory tract infections) at the start of AVM0703 administration, including the following:
* Positive hepatitis B surface antigen and/or hepatitis B core antibody test plus a positive hepatitis B polymerase chain reaction (PCR) assay. Patients with a negative PCR assay are permitted with appropriate antiviral prophylaxis;
* Positive hepatitis C virus antibody (HCV Ab) test. Patients with a positive HCV Ab test are eligible if they are negative for hepatitis C virus by PCR;
* Positive human immunodeficiency virus (HIV) antibody test with detectable HIV load by PCR, or the patient is not able to tolerate antiretroviral therapy; or
* Positive tuberculosis test during screening; test must be positive and not indeterminate due to anergy; if the result is indeterminate due to anergy the patient must not have a history of recent exposure to tuberculosis. Patients in Phase 2 repeat dosing cohorts should not travel to any destination where they might be exposed to tuberculosis during their entire treatment period with AVM0703.
8. Received live vaccination within 8 weeks of screening;
9. Pregnant or breastfeeding;
10. Concurrent participation in another therapeutic clinical study (except AVM0703-001); or
11. Uncontrolled bipolar disorder or schizophrenia. Patients with a diagnosis, past or current, of bipolar disorder or schizophrenia or having a history of severe depression or substance abuse must be prophylactically treated with circadian physiologic hydrocortisone per section 5.5.3.3 CNS prophylaxis, without exception.

Contacts and Locations

Study Contact

Peter Jarzyna, PharmD

CONTACT

206-639-9239

pjarzyna@avmbiotech.com

Theresa A Deisher, PhD

CONTACT

206 851 3942

tdeisher@avmbiotech.com

Principal Investigator

Elizabeth Budde, MD

PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Gary Schiller, MD

PRINCIPAL_INVESTIGATOR

University of California, Los Angeles

Tamra Slone, MD

PRINCIPAL_INVESTIGATOR

U Texas SouthWestern

Don Stevens, MD

PRINCIPAL_INVESTIGATOR

Norton Cancer Institute

Lasika Seneviratne, MD

PRINCIPAL_INVESTIGATOR

Los Angeles Cancer Network

Pamela Miel, MD

PRINCIPAL_INVESTIGATOR

Innovative Clinical Research Institute

Stefano Tarantolo, MD

PRINCIPAL_INVESTIGATOR

Nebraska Cancer Specialists

Daniel Kerr, MD

PRINCIPAL_INVESTIGATOR

ASCLEPES Research Centers

Nashat Gabrail, MD

PRINCIPAL_INVESTIGATOR

Gabrail Cancer Center Research

Paul Rubinstein, MD

PRINCIPAL_INVESTIGATOR

University of Illinois at Chicago

Salil Goorha, MD

PRINCIPAL_INVESTIGATOR

Memphis Baptist Cancer Center

Study Locations (Sites)

City of Hope

Duarte, California, 91010

United States

Los Angeles Cancer Network

Los Angeles, California, 90017

United States

UCLA Medical Center of Hematology/Oncology

Los Angeles, California, 90095

United States

Innovative Clinical Research Institute

Whittier, California, 92705

United States

ASCLEPES Research Centers

Weeki Wachee, Florida, 34613

United States

University of Illinois at Chicago Cancer Center

Chicago, Illinois, 60612

United States

Norton Cancer Institute

Louisville, Kentucky, 40207

United States

Oncology Hematology West P.C. dba Nebraska Cancer Specialists

Omaha, Nebraska, 68124

United States

Gabrail Cancer Center Research,

Canton, Ohio, 44718

United States

Baptist Clinical Research Institute

Memphis, Tennessee, 38120

United States

University of Texas(UT) Southwestern-Children's Medical Center

Dallas, Texas, 75235

United States

Collaborators and Investigators

Sponsor: AVM Biotechnology Inc

Elizabeth Budde, MD, PRINCIPAL_INVESTIGATOR, City of Hope Medical Center
Gary Schiller, MD, PRINCIPAL_INVESTIGATOR, University of California, Los Angeles
Tamra Slone, MD, PRINCIPAL_INVESTIGATOR, U Texas SouthWestern
Don Stevens, MD, PRINCIPAL_INVESTIGATOR, Norton Cancer Institute
Lasika Seneviratne, MD, PRINCIPAL_INVESTIGATOR, Los Angeles Cancer Network
Pamela Miel, MD, PRINCIPAL_INVESTIGATOR, Innovative Clinical Research Institute
Stefano Tarantolo, MD, PRINCIPAL_INVESTIGATOR, Nebraska Cancer Specialists
Daniel Kerr, MD, PRINCIPAL_INVESTIGATOR, ASCLEPES Research Centers
Nashat Gabrail, MD, PRINCIPAL_INVESTIGATOR, Gabrail Cancer Center Research
Paul Rubinstein, MD, PRINCIPAL_INVESTIGATOR, University of Illinois at Chicago
Salil Goorha, MD, PRINCIPAL_INVESTIGATOR, Memphis Baptist Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-11-06

Study Completion Date2025-06-01

Study Record Updates

Study Start Date2020-11-06

Study Completion Date2025-06-01

Terms related to this study

Keywords Provided by Researchers

Diffuse large B-cell lymphoma (DLBCL)
B-cell lymphoma
Mantle cell lymphoma (MCL)
Primary mediastinal large B-cell Lymphoma
Primary DLBCL of the central nervous system (CNS)
Burkitt or Burkitt-like lymphoma/leukemia
Chronic lymphocytic leukemia (CLL)
Small lymphocytic leukemia (SLL)
B-cell leukemia/lymphoma
T-cell leukemia/lymphoma
Acute leukemias of ambiguous lineage
Natural Killer (NK) cell lymphoblastic leukemia/lymphoma
Advanced or Aggressive lymphoma/lymphoproliferative disease
Follicular Lymphoma

Additional Relevant MeSH Terms

Lymphoid Malignancies