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This Phase Ia/Ib, open-label, multicenter study will evaluate the safety, tolerability, and preliminary efficacy of DCLL9718S as a single agent (Phase Ia, Arm A) in participants with relapsed or refractory AML or in combination with azacitidine (Phase Ib, Arm B) in participants with previously untreated AML who are not eligible for intensive induction chemotherapy. Each arm will consist of two stages: a dose-escalation stage and an expansion stage. The dose-escalation stage is designed to establish the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) for DCLL9718S alone (Arm A) or in combination with azacitidine (Arm B). The dose-expansion stage is designed to characterize the long-term safety and tolerability of DCLL9718S.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A: DCLL9718S | Experimental | Participants will receive escalating doses of DCLL9718S intravenously (IV) in each 21-day cycle to determine MTD and RP2D in dose-escalation stage followed by DCLL9718S IV at RP2D in each 21-day cycle in dose-expansion stage until disease progression, unacceptable toxicity, or any other discontinuation criteria are met. |
|
| Arm B: DCLL9718S and Azacitidine | Experimental | Participants will receive escalating doses of DCLL9718S (starting dose: at least one dose level below a completed and tolerated DCLL9718S monotherapy in Arm A) IV in each 28-day cycle and azacitidine 75 milligrams per square meter (mg/m^2) subcutaneously (SC) or IV on Days 1-7 of each 28-day cycle to determine MTD and RP2D of DCLL9718S in dose-escalation stage followed by DCLL9718S IV at RP2D in each 28-day cycle and azacitidine 75 mg/m^2 SC or IV on Days 1-7 of each 28-day cycle in dose-expansion stage until disease progression, unacceptable toxicity, or any other discontinuation criteria are met. Azacitidine may also be given on Days 1-5 and Days 8-9 depending on institutional preference. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| DCLL9718S | Drug | DCLL9718S will be administered as per the schedule specified in the respective arm. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of participants With Adverse Events (AEs) | Baseline up to end of study (up to approximately 3 years) | |
| Percentage of Participants With Dose-Limiting Toxicities (DLTs) | Cycle 1 Day 1 up to Cycle 2 Day 1 (Cycle length: 21 days for Arm A and 28 days for Arm B) | |
| MTD of DCLL9718S | Cycle 1 Day 1 up to Cycle 2 Day 1 (Cycle length: 21 days for Arm A and 28 days for Arm B) | |
| RP2D of DCLL9718S | Cycle 1 Day 1 up to Cycle 2 Day 1 (Cycle length: 21 days for Arm A and 28 days for Arm B) |
| Measure | Description | Time Frame |
|---|---|---|
| Serum Concentration of DCLL9718S | up to 3 years | |
| Plasma Concentration of Azacitidine | up to 3 years | |
| Area Under the Concentration-Time Curve (AUC) of DCLL9718S |
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Inclusion Criteria:
Specifically for participants in Arm A:
Specifically for participants in Arm B:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| City of Hope | Duarte | California | 91010 | United States | ||
| University of Colorado Hospital - Anschutz Cancer Pavilion |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33617672 | Derived | Daver N, Salhotra A, Brandwein JM, Podoltsev NA, Pollyea DA, Jurcic JG, Assouline S, Yee K, Li M, Pourmohamad T, Samineni D, Sumiyoshi T, Vaze A, Dere RC, Ma C, Cooper J. A Phase I dose-escalation study of DCLL9718S, an antibody-drug conjugate targeting C-type lectin-like molecule-1 (CLL-1) in patients with acute myeloid leukemia. Am J Hematol. 2021 May 1;96(5):E175-E179. doi: 10.1002/ajh.26136. Epub 2021 Mar 11. No abstract available. |
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| Azacitidine | Drug | Azacitidine will be administered as per the schedule specified in the respective arm. |
|
|
| up to 3 years |
| Maximum Plasma Concentration Observed (Cmax) of DCLL9718S | up to 3 years |
| Total Clearance of DCLL9718S | up to 3 years |
| Terminal Half-Life (t1/2) of DCLL9718S | up to 3 years |
| Volume of Distribution Under Steady-State (Vss) of DCLL9718S | up to 3 years |
| Percentage of Participants With Complete Remission (CR), CR With Incomplete Blood Count Recovery (CRi), CR With Incomplete Platelet Count Recovery (CRp), and Overall Response, Assessed as per International Working Group (IWG) Criteria | From the date of first treatment to disease progression or relapse or death from any cause (up to approximately 3 years) |
| Duration of Response, Assessed as per IWG Criteria | From the date of first response to the earliest recurrence or disease progression (up to approximately 3 years) |
| Overall Survival | From the date of first treatment to the date of death from any cause (up to approximately 3 years) |
| Event-Free Survival (EFS), Assessed as per IWG Criteria | From the date of first treatment until treatment failure, relapsed from CR, CRp, or CRi, or death from any cause, whichever occurs first (up to approximately 3 years) |
| Progression-Free Survival (PFS), Assessed as per IWG Criteria | From the date of first treatment to disease progression or relapse or death from any cause (up to approximately 3 years) |
| Change From Baseline in Anti-Drug Antibody (ADA) to DCLL9718S | Baseline up to end of study (up to approximately 3 years) |
| Aurora |
| Colorado |
| 80045 |
| United States |
| Yale School of Medicine | New Haven | Connecticut | 06510 | United States |
| Columbia University Medical Center; Research Pharmacy, Irving Pavillion, Ip 7-749 | New York | New York | 10032 | United States |
| MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| University of Alberta Hospital | Edmonton | Alberta | T6G 1C9 | Canada |
| Princess Margaret Hospital; Department of Med Oncology | Toronto | Ontario | M5G 2M9 | Canada |
| Jewish General Hospital / McGill University | Montreal | Quebec | H3T 1E2 | Canada |
| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| C000717290 | DCLL9718S |
| D001374 | Azacitidine |
| ID | Term |
|---|---|
| D001372 | Aza Compounds |
| D009930 | Organic Chemicals |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
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