Study of 3D189 in Patients With Hematologic Malignancies

Phase 1

Active, not recruiting

• Conditions: Acute Leukemia; Multiple Myeloma; Non-Hodgkin Lymphoma; Higher-risk Myelodysplastic Syndrome

• Registration Number: NCT05320809
• Lead Sponsor: 3D Medicines

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-3-19
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: Active, not recruiting
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

Inclusion Criteria:<br><br> - Subjects must be willing and able to understand and provide signed informed consent<br> for the study.<br><br> - Male or female patients = 18 years of age on the day of signing informed consent.<br><br> - Have a histologically or cytologically confirmed hematological malignancy and have<br> achieved complete remission (CR) or partial remission (PR) after at least one line<br> of standard therapy, and are not suitable for hematopoietic stem cell transplant<br> (HSCT) for the following reasons: a) not eligible for HSCT due to intercurrent<br> medical conditions; b) lack of an available HLA-matched donor for allogeneic HSCT;<br> c) not able to accept HSCT for financial reasons; d) without a potential indication<br> for HSCT (e.g. having a relatively favorable prognosis or low risk of relapse).<br> However, patients who have previously received autologous HSCT but remain MRD+ or in<br> remission after salvage therapy for post-transplant relapse are allowed to be<br> recruited.<br><br>Including the following 4 types of hematological malignancies:<br><br> 1. Acute Leukemia (AL): including acute myeloma leukemia (AML) and acute lymphoblastic<br> leukemia (ALL), in morphological complete remission with complete or incomplete<br> blood count recovery (CR or CRi), and having completed any planned post-remission<br> therapy;<br><br> 2. Myelodysplastic Syndrome (MDS): Revised International Prognostic Scoring System<br> (IPSS-R) risk score > 3.5, having achieved CR or PR following prior therapy;<br><br> 3. Multiple Myeloma (MM): having achieved stringent complete response (sCR), CR or very<br> good partial response (VGPR), or PR if deeper response cannot be obtained from<br> adequate therapy.<br><br> 4. Non-Hodgkin Lymphoma (NHL): preference for patients with diffuse large B-cell<br> lymphoma (DLBCL) and follicular lymphoma (FL) who have achieved CR or PR following<br> prior therapy.<br><br> - Have a documented WT1 positive disease. This is defined as detectable presence<br> of WT1 transcript via real-time quantitative polymerase chain reaction (RT-PCR)<br> in patients'bone marrow or peripheral blood samples, or WT1 expression by<br> immunohistochemistry (IHC) in archived (paraffin embedded, unstained slides) or<br> freshly biopsied tumor tissues from bone marrow or lymph nodes or extranodal<br> lesions ( for NHL patients).<br><br> - Eastern Cooperative Oncology Group (ECOG) performance status of 0~1.<br><br> - Estimated life expectancy = 6 months.<br><br> - The interval between the last antitumor therapy (including surgery,<br> radiotherapy and systemic therapy) and the first study treatment must be at<br> least 4 weeks or 10 half-lives of chemotherapy drugs (whichever is shorter),<br> and the toxicity of the previous therapies have recovered to = grade 1<br> [according to the Common Terminology Criteria for Adverse Events (CTCAE) 5.0],<br> except for toxicity such as alopecia, which in the judgment of the investigator<br> is not a safety risk.<br><br> - Have adequate organ and bone marrow function, defined as follows:<br><br> 1) Blood count (participants must not have received transfusion of blood products<br> within 7 days prior to this test): hemoglobin (Hb) = 9.0 g/dL; neutrophil (NEUT) =<br> 1.0×109/L; platelet (PLT) = 50×109/L; 2) Liver function: alanine aminotransferase<br> (ALT) and aspartate aminotransferase (AST) = 2.5 ×ULN (upper limit of normal); but<br> for subjects with liver metastasis, ALT or AST = 5×ULN; total bilirubin (TBIL) = 1.5<br> × ULN, or TBIL > 1.5 × ULN, but direct bilirubin (DBIL) = 1.0 × ULN; 3) Renal<br> function: serum creatinine = 1.5 × ULN or endogenous creatinine clearance rate = 50<br> ml/min (Cockcroft-Gault formula); 4) Coagulation: international normalized ratio<br> (INR) = 1.5, activated partial thromboplastin time (APTT) = 1.5 ×ULN, unless<br> subjects are receiving anticoagulant therapy as long as INR or APTT is within the<br> therapeutic range of intended use of anticoagulants; 5) Cardiac function: left<br> ventricular ejection fraction (LVEF) = 50% by echocardiography.<br><br>• Subjects (including partners) must agree to use an adequate method of contraception,<br>starting with the screening visit through 4 months after the last dose of study<br>treatment.<br><br>Exclusion Criteria:<br><br> - Previously treated with any therapy targeting WT1.<br><br> - Have known hypersensitivity to peptide biologics, or to immune adjuvants Montanide<br> and/or GM-CSF.<br><br> - Subjects with acute promyelocytic leukemia (APL or M3).<br><br> - Presence of central nervous system (CNS) invasion and/or carcinomatous meningitis;<br> participants with previously cured brain or meningeal metastasis can be allowed.<br><br> - Have undergone prior allogeneic HSCT, or plan to perform HSCT during the study<br> period.<br><br> - Received live vaccine within 4 weeks prior to the first dose of study treatment.<br><br> - Currently participate in or have participated in a study of an interventional agent<br> or device within 4 weeks prior to the first dose of study treatment.<br><br> - Have a known additional malignancies within the past 5 years, with the exception of<br> cured skin basal cell carcinoma or cervical cancer in situ or other carcinoma in<br> situ.<br><br> - Have an active autoimmune disease or any disease that requires long-term use of<br> systemic corticosteroids (at doses greater than 10 mg daily of prednisone<br> equivalent) or any other form of immunosuppressive agents, hormone replacement<br> therapy for adrenocortical insufficiency, hypopituitarism, hypothyroidism, or type I<br> diabetes mellitus is not considered a form of systemic treatment and is allowed.<br><br> - Have a diagnosis of primary immunodeficiency disease, or acquired immunodeficiency<br> syndrome, or a positive test for human immunodeficiency virus (HIV).<br><br> - Presence of active tuberculosis.<br><br> - Have a history of a severe cardiovascular disease such as class III or IV heart<br> failure [New York Heart Association (NYHA) criteria], myocardial infarction or<br> stroke, unstable angina within 6 months prior to start of study treatment.<br><br> - QTcF interval tested during the screening period = 450 msec (for male subjects) or =<br> 470 msec (for female).<br><br> - Have an acute severe infection requiring systemic therapy during the screening<br> period.<br><br> - Positive for HBsAg and HBV DNA = 103 IU/ml; or positive for HCV antibodies and HCV<br> RNA level is above the detection limit.<br><br> - Are pregnant or breastfeeding, or have a positive serum pregnancy test during the<br> screening period (for female subjects of childbearing potential).<br><br> - Have a known psychiatric or substance abuse disorder that would interfere with the<br> participant's ability to cooperate with the requirements of the study.<br><br> - Any condition, therapy or laboratory abnormality that, in the opinion of the<br> investigator, might affect the participant's compliance, pose an unwarranted high<br> risk to the participant, or interfere with the interpretation of the study results.

Exclusion Criteria

Not provided

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Number and frequency of TRAEs, including AE and SAEs (safety parameters);Immune response rate of 3D189 vaccination among subjects

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS);Relapse-free survival (RFS) or progression-free survival (PFS);Overall response rate (ORR);Duration of Response (DoR);Disease control rate (DCR)