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The WWRD Study: AVM0703 for Treatment of Leukemia or Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04329728
Recruitment Status : Not yet recruiting
First Posted : April 1, 2020
Last Update Posted : May 29, 2020
Sponsor:
Collaborator:
Medpace, Inc.
Information provided by (Responsible Party):
AVM Biotechnology LLC

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Lymphoid Malignancies Drug: Supra-Pharmacologic Dexamethasone sodium phosphate Drug: Hydrocortisone Drug: Proton pump inhibitor Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 144 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Phase 1/2 Study Evaluating AVM0703 in Patients With Lymphoid Malignancies (WWRD Study)
Estimated Study Start Date : June 2020
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : June 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: • DLBCL and high-grade B-cell lymphoma Drug: Supra-Pharmacologic Dexamethasone sodium phosphate
Intravenous infusion over 1-2 hours
Other Name: AVM0703

Drug: Hydrocortisone
Physiologic circadian hydrocortisone will be administered from day of AVM0703 infusion for 5 days to prevent neuropsychiatric side effects according to published clinical trial results of Warris et. al. 2016.

Drug: Proton pump inhibitor
A proton pump inhibitor or H2 blocker starting at least 1 day prior to and for approximately 4 weeks after AVM0703 administration, as per institutional guidelines.

Experimental: • MCL Drug: Supra-Pharmacologic Dexamethasone sodium phosphate
Intravenous infusion over 1-2 hours
Other Name: AVM0703

Drug: Hydrocortisone
Physiologic circadian hydrocortisone will be administered from day of AVM0703 infusion for 5 days to prevent neuropsychiatric side effects according to published clinical trial results of Warris et. al. 2016.

Drug: Proton pump inhibitor
A proton pump inhibitor or H2 blocker starting at least 1 day prior to and for approximately 4 weeks after AVM0703 administration, as per institutional guidelines.

Experimental: • Primary mediastinal large B-cell lymphoma Drug: Supra-Pharmacologic Dexamethasone sodium phosphate
Intravenous infusion over 1-2 hours
Other Name: AVM0703

Drug: Hydrocortisone
Physiologic circadian hydrocortisone will be administered from day of AVM0703 infusion for 5 days to prevent neuropsychiatric side effects according to published clinical trial results of Warris et. al. 2016.

Drug: Proton pump inhibitor
A proton pump inhibitor or H2 blocker starting at least 1 day prior to and for approximately 4 weeks after AVM0703 administration, as per institutional guidelines.

Experimental: • Burkitt or Burkitt-like lymphoma/leukemia Drug: Supra-Pharmacologic Dexamethasone sodium phosphate
Intravenous infusion over 1-2 hours
Other Name: AVM0703

Drug: Hydrocortisone
Physiologic circadian hydrocortisone will be administered from day of AVM0703 infusion for 5 days to prevent neuropsychiatric side effects according to published clinical trial results of Warris et. al. 2016.

Drug: Proton pump inhibitor
A proton pump inhibitor or H2 blocker starting at least 1 day prior to and for approximately 4 weeks after AVM0703 administration, as per institutional guidelines.

Experimental: • CLL/SLL Drug: Supra-Pharmacologic Dexamethasone sodium phosphate
Intravenous infusion over 1-2 hours
Other Name: AVM0703

Drug: Hydrocortisone
Physiologic circadian hydrocortisone will be administered from day of AVM0703 infusion for 5 days to prevent neuropsychiatric side effects according to published clinical trial results of Warris et. al. 2016.

Drug: Proton pump inhibitor
A proton pump inhibitor or H2 blocker starting at least 1 day prior to and for approximately 4 weeks after AVM0703 administration, as per institutional guidelines.

Experimental: B or T ALL
• B-lymphoblastic leukemia/lymphoma, T-lymphoblastic leukemia/lymphoma, acute leukemia/lymphoma, acute leukemias of ambiguous lineage, or natural killer (NK) cell lymphoblastic leukemia/lymphoma
Drug: Supra-Pharmacologic Dexamethasone sodium phosphate
Intravenous infusion over 1-2 hours
Other Name: AVM0703

Drug: Hydrocortisone
Physiologic circadian hydrocortisone will be administered from day of AVM0703 infusion for 5 days to prevent neuropsychiatric side effects according to published clinical trial results of Warris et. al. 2016.

Drug: Proton pump inhibitor
A proton pump inhibitor or H2 blocker starting at least 1 day prior to and for approximately 4 weeks after AVM0703 administration, as per institutional guidelines.




Primary Outcome Measures :
  1. Phase 1: incidence of Adverse events [ Time Frame: Year One ]
    The primary endpoint for the Phase 1 portion of the study is the incidence of Adverse events (AEs), including DLTs.


Secondary Outcome Measures :
  1. Phase 2: ORR [ Time Frame: Year Two ]
    ORR (CR plus partial response [PR]) at 28 days post infusion



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years to 95 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion 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 R/R disease with prior therapies defined below:

    • DLBCL and high-grade B-cell lymphoma:

      1. R/R after autologous HCT; or
      2. R/R after CAR T therapy; or
      3. Ineligible for autologous HCT or CAR T therapy due to persistent disease, co-morbidity, or social issues (eg, lack of insurance, lack of caregiver, etc); or
      4. R/R after ≥2 lines of therapy including anti-20 antibody. Patients must have failed or are intolerant or ineligible for polatuzamab vedotin;
    • MCL:

      1. R/R after autologous HCT; or
      2. Ineligible for autologous HCT due to persistent disease, co-morbidity, or social issues (eg, lack of insurance, lack of caregiver, etc); or
      3. R/R after ≥2 lines of therapy including at least 1 of the following: a BTK inhibitor, bortezomib, or lenalidomide;
    • Primary mediastinal large B-cell lymphoma:

      a. R/R after ≥1 line of therapy; AVM Biotechnology, LLC. Clinical Study Protocol AVM0703-001 Confidential & Proprietary Page 47 of 105 Version 1.0, 20 February 2020

    • Primary DLBCL of the CNS:

      a. R/R after ≥1 line of therapy including methotrexate (unless intolerant to methotrexate);

    • Burkitt or Burkitt-like lymphoma/leukemia:

      1. R/R after autologous or allogeneic HCT; or
      2. Ineligible for autologous or allogeneic HCT due to persistent disease, co-morbidity, or social issues (eg, lack of insurance, lack of caregiver, etc);
    • CLL/SLL:

      1. R/R after autologous or allogeneic HCT; or
      2. Ineligible for autologous or allogeneic HCT due to persistent disease, co-morbidity, or social issues (eg, lack of insurance, lack of caregiver, etc); or
      3. R/R after ≥2 lines of therapy including at least 1 of the following: a BTK inhibitor, ventoclax, idelalisib, or duvelisib;
    • ALL:

      1. R/R after autologous or allogeneic HCT; or
      2. Ineligible for allogeneic HCT due to persistent disease, co-morbidity, or social issues (eg, lack of insurance, lack of caregiver, etc); or
      3. R/R according to the following disease-specific specifications:
    • B-cell lymphoblastic leukemia/lymphoma: ≥2 lines of therapy including approved CAR T cell therapies, inotuzumab, ozogamicin, or blinatumomab; or
    • T-cell lymphoblastic leukemia/lymphoma: Patients must have failed nelarabine; or
    • NK cell lymphoblastic leukemia/lymphoma: R/R after ≥1 line of therapy;

      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 ≥0.5 × 109/L;
    • Platelet count >50 × 109/L;
    • Hemoglobin ≥8.0 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
    • Serum creatinine ≤1.5 × ULN or glomerular filtration rate ≥50 mL/min (calculated from a 24-hour urine collection);

      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.

Exclusion Criteria:

  • Patients who meet any of the following criteria will be excluded from participation in the study:

    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 (eg, 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 [DBP] ≥100 mmHg or systolic blood pressure [SBP] ≥150 mmHg) despite antihypertensive therapy for patients ≥18 years of age, or uncontrolled stage 2 hypertension (DBP ≥90 mmHg or SBP ≥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, left bundle-branch block, second-degree atrioventricular (AV) block type 2, third-degree AV block, ≥Grade 2 bradycardia, or heart rate corrected QT interval using Fridericia's formula average of triplicate ECGs >450 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 testing for tuberculosis during screening;
    8. Received live vaccination within 8 weeks of screening;
    9. Pregnant or breastfeeding;
    10. Concurrent participation in another therapeutic clinical study; or
    11. Manic-depressive disorder, schizophrenia, or a history of severe depression or substance abuse.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04329728


Contacts
Layout table for location contacts
Contact: Madhavi Malladi, PhD 1.513-384-6717 M.Malladi@Medpace.com
Contact: Bethelhem Lebneh 2069069922 blebneh@avmbiotech.com

Sponsors and Collaborators
AVM Biotechnology LLC
Medpace, Inc.
Investigators
Layout table for investigator information
Principal Investigator: Nicholas Short, MD MD Anderson
Principal Investigator: Elizabeth Budde, MD City of Hope Medical Center
Principal Investigator: Gary Schiller, MD University of California, Los Angeles
Principal Investigator: Farrukh T Awan, MD U Texas SouthWestern
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Responsible Party: AVM Biotechnology LLC
ClinicalTrials.gov Identifier: NCT04329728    
Other Study ID Numbers: AVM0703-001
First Posted: April 1, 2020    Key Record Dates
Last Update Posted: May 29, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms
Dexamethasone
Hydrocortisone
Dexamethasone acetate
Dexamethasone 21-phosphate
Proton Pump Inhibitors
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protease Inhibitors