A Safety Study of SEA-CD70 in Patients With Myeloid Malignancies

Acute Myeloid Leukemia Clinical Trial

Official title:

A Phase 1 Study of SEA-CD70 in Myeloid Malignancies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04227847
• Other study ID #: SGNS70-101
• Secondary ID: 2019-001917-18
• Status: Recruiting
• Phase: Phase 1
• Start date: August 7, 2020
• Est. completion date: November 30, 2026

Study information

• Verified date: May 2024
• Source: Seagen Inc.
• Contact: Seagen Trial Information Support
• Phone: 866-333-7436
• Email: clinicaltrials[@]seagen.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial will look at a drug called SEA-CD70 with and without azacitidine, to find out if it is safe for patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). It will study SEA-CD70 to find out what its side effects are and if it works for AML and MDS. A side effect is anything the drug does besides treating cancer.

This study will have six groups or "parts."

• Part A will find out how much SEA-CD70 should be given to patients.

• Part B will use the dose found in Part A to find out how safe SEA-CD70 is and if it works to treat patients with MDS.

• Part C will use the dose found in Part A to find out how safe SEA-CD70 is and if it works to treat patients with AML.

• Part D will find out how much SEA-CD70 with azacitidine should be given to patients.

• Part E will use the dose found in Part D to find out how safe SEA-CD70 with azacitidine is and if it works to treat patients with MDS or MDS/AML that has not been treated.

• Part F will use the dose found in Part D to find out how safe SEA-CD70 with azacitidine is and if it works to treat patients with MDS or MDS/AML.

Description:

This is a phase 1, open-label, multicenter, dose-finding, and dose expansion study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and antitumor activity of SEA-CD70 monotherapy and SEA-CD70 in combination with azacitidine in adults with myeloid malignancies. The study will be conducted in up to 6 parts.

• Part A is a dose-escalation cohort designed to identify the MTD or recommended expansion dose of SEA-CD70 monotherapy in participants with relapsed/refractory (hypomethylating agent [HMA]-failure) MDS.

• Part B is an expansion cohort designed to evaluate the safety and tolerability of SEA-CD70 monotherapy in participants with relapsed/refractory (HMA-failure) MDS.

• Part C is an expansion cohort designed to evaluate the safety and tolerability of SEA-CD70 monotherapy in participants with relapsed/refractory AML.

• Part D contains dose-finding/dose optimization cohorts designed to evaluate the safety/tolerability and identify the recommended expansion dose of SEA-CD70 in combination with azacitidine in participants with 1) relapsed/refractory (HMA-failure) MDS or MDS/AML, and 2) previously untreated higher-risk per IPSS-M (Moderate High, High or Very High) MDS or MDS/AML.

• Part E is an expansion cohort designed to evaluate the safety and tolerability of SEA-CD70 in combination with azacitidine in participants with previously untreated higher-risk per IPSS-M (Moderate High, High, or Very High) MDS or MDS/AML.

• Part F is an expansion cohort designed to evaluate the safety and tolerability of SEA-CD70 in combination with azacitidine in participants with relapsed/refractory (HMA-failure) MDS or MDS/AML.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 140
• Est. completion date: November 30, 2026
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Part A Inclusion Criteria

• Participants with cytologically/histologically confirmed MDS according to the 2016 World Health Organization (WHO) classification with the following:

• Measurable disease per WHO MDS with excess blasts criteria as defined either:

• 5%-9% blasts in the bone marrow or 2%-4% blasts in the peripheral blood or

• 10%-19% blasts in the bone marrow or 5%-19% blasts in the peripheral blood

• MDS that is relapsed or refractory and must not have other therapeutic options known to provide clinical benefit in MDS available.

• Treatment failure after prior hypomethylating agent (HMA) therapy for MDS, defined as one of the following:

• Progression (per 2006 International Working Group [IWG] criteria) at any time after initiation of HMA therapy.

• Lack of response (failure to achieve complete remission [CR], partial response [PR], or hematologic improvement [HI] per 2006 IWG criteria) after at least 6 cycles of azacitidine (or equivalent HMA) or 4 cycles of decitabine (or equivalent HMA).

• Relapse after achievement of CR, PR, or HI (per 2006 IWG criteria).

• Intolerance of HMA (Grade 3 or higher non-hematologic toxicity leading to treatment discontinuation).

• Participants with isolated 5q-/5q- syndrome must have progressed, failed, relapsed, or not tolerated lenalidomide in addition to HMA.

• Must be off HMA therapy = 2 weeks and must be off any other treatments for MDS for = 4 weeks prior to first dose of SEA-CD70; growth factors and transfusions are allowed before and during the study as clinically indicated

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

Part B Inclusion Criteria

• Participants with cytologically/histologically confirmed MDS according to the WHO classification with the following:

• Measurable disease per WHO MDS with excess blasts (MDS-EB) criteria as defined either:

• 5%-9% blasts in the bone marrow or 2%-4% blasts in the peripheral blood, or

• 10%-19% blasts in the bone marrow or 5%-19% blasts in the peripheral blood

• MDS that is relapsed or refractory and must not have other therapeutic options known to provide clinical benefit in MDS available.

• Treatment failure after prior HMA therapy for MDS defined as one of the following:

• Progression (per 2006 IWG criteria) at any time after initiation of HMA therapy.

• Lack of response (failure to achieve CR, PR, or HI per 2006 IWG criteria) after at least 6 cycles of azacitidine or 4 cycles of decitabine.

• Relapse after achievement of CR, PR, or HI (per 2006 IWG criteria).

• Intolerance of HMA (Grade 3 or higher non-hematologic toxicity leading to treatment discontinuation).

• Participants with isolated 5q-/5q- syndrome must have progressed, failed, relapsed, or not tolerated lenalidomide in addition to HMA.

• Must be off HMA therapy = 2 weeks and must be off any other systemic treatments for MDS for = 4 weeks prior to first dose of SEA-CD70; growth factors and transfusions are allowed before and during the study as clinically indicated.

• ECOG Performance Status of 0-2

Part C Inclusion Criteria

• Participants with relapsed or refractory AML according to International Consensus Classification (ICC) 2022 (except for acute promyelocytic leukemia [APL]):

• Who have received either 2 or 3 previous regimens to treat active disease. Post-remission treatments, intrathecal chemotherapy, and radiotherapy are not considered previous regimens.

• Who have received 1 previous regimen to treat active disease and have at least one of the following:

• Age > 60 and =75 years.

• Primary resistant AML (defined as failure to achieve CR after 1-2 courses of induction therapy)

• First CR duration <6 months

• Adverse-risk per European Leukemia Network genetic risk stratification

• Secondary AML (prior history of MDS or therapy-related)

• Age 18-75 years

• ECOG performance status of 0-2

Parts D and F Inclusion Criteria

• Participants with diagnosis of MDS or MDS/AML according to ICC 2022 criteria

• Disease which has relapsed, failed to respond after minimum of 6 cycles, or progressed following an HMA in the immediately preceding line of therapy.

• Eligible for continued therapy with azacitidine

• Must be off any other systemic treatment for AML/MDS. Must be off HMA therapy = (greater than or equal to) 2 weeks and any other systemic treatments for MDS for = (greater than or equal to) 4 weeks prior to first dose of SEA-CD70

• ECOG Performance Status 0-2

Parts D and E Inclusion Criteria

• Participants with diagnosis of MDS or MDS/AML according to ICC 2022 criteria, previously untreated.

• Participants with MDS/AML should not have AML-defining cytogenetics.

• Participants with higher-risk (Moderate High, High, or Very High) per Molecular International Prognostic Scoring System (IPSS-M) MDS and MDS/AML

• ECOG Performance Status 0-2

Exclusion Criteria (All Parts)

• History of another malignancy within 3 years before the first dose of study drug or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk of metastasis or death.

• Previous exposure to CD70-targeted agents

• Prior allogeneic hematopoietic stem cell transplant, for any condition

• Central nervous system leukemia based on imaging or documented positive cytology in cerebral spinal fluid

• History of clinically significant sickle cell anemia, autoimmune hemolytic anemia, or idiopathic thrombocytopenic purpura

• Parts D and F only: Prior oral HMA or oral HMA-combinations

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes

Intervention

Drug:
• SEA-CD70
Given into the vein (IV; intravenously) on Days 1 and 15 of each treatment cycle
• azacitidine
75mg/m^2 injected under the skin (SC; subcutaneous) or given into the vein (IV; intravenously) on Days 1 through 7 of each treatment cycle.

Locations

Country	Name	City	State
Netherlands	Leids Universitair Medisch Centrum ( LUMC)	Leiden	Other
Netherlands	University Medical Center (UMC) Utrecht	Utrecht	Other
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Medical University of South Carolina/Hollings Cancer Center	Charleston	South Carolina
United States	Cleveland Clinic, The	Cleveland	Ohio
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	James Cancer Hospital / Ohio State University	Columbus	Ohio
United States	Texas Oncology - Fort Worth	Dallas	Texas
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	Karmanos Cancer Institute / Wayne State University	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	University of Kansas Cancer Center	Fairway	Kansas
United States	San Juan Oncology Associates	Farmington	New Mexico
United States	Saint Francis Hospital / Bon Secours - South Carolina	Greenville	South Carolina
United States	Houston Methodist Cancer Center	Houston	Texas
United States	MD Anderson Cancer Center / University of Texas	Houston	Texas
United States	UCLA Department of Medicine - Hematology & Oncology	Los Angeles	California
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Tennessee Oncology-Nashville/Sarah Cannon Research Institute	Nashville	Tennessee
United States	Columbia University Medical Center	New York	New York
United States	Swedish Cancer Institute	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Seagen Inc.

Countries where clinical trial is conducted

United States,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with adverse events (AEs)	Any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment.	Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
Primary	Number of participants with laboratory abnormalities	To be summarized using descriptive statistics.	Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
Primary	Number of participants with a dose-limiting toxicity (DLT) at each dose level (Parts A and D only)	To be summarized using descriptive statistics.	Though end of DLT evaluation period; up to approximately 4 weeks
Secondary	AUC - Area under the plasma concentration-time curve	To be summarized using descriptive statistics.	Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
Secondary	Tmax - Time to maximum concentration attained	To be summarized using descriptive statistics.	Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
Secondary	Cmax - Maximum observed plasma concentration	To be summarized using descriptive statistics.	Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
Secondary	Ctrough - Minimum plasma concentration per dosing interval	To be summarized using descriptive statistics.	Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
Secondary	T1/2 - Terminal elimination half-life	To be summarized using descriptive statistics.	Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
Secondary	Incidence of antidrug antibodies (ADA)	To be summarized using descriptive statistics.	Through 30-37 days following last dose of SEA-CD70; up to approximately 2 years
Secondary	Complete remission (CR) Rate and complete remission equivalent (CReq) rate	Proportion of participants with AML, MDS/AML or MDS who achieve CR or CReq	Up to approximately 4 years
Secondary	Complete remission with incomplete blood count recovery (CRi) rate	Proportion of participants with AML who achieve CRi	Up to approximately 4 years
Secondary	Complete remission with limited count recovery (CRL) rate for participants with MDS or MDS/AML	Proportion of participants with MDS or MDS/AML who achieve CRL	Up to approximately 4 years
Secondary	Complete remission with partial hematologic recovery (CRh) rate	Proportion of participants with AML, MDS/AML, or MDS who achieve CRh	Up to approximately 4 years
Secondary	Hematologic response (HI) rate	Proportion of participants with MDS or MDS/AML with HI	Up to approximately 4 years
Secondary	Overall response rate (ORR)	For AML, the proportion of participants who achieve a best response of CR, CRi, CRh, or partial response (PR). For MDS, the proportion of participants who achieve a best response of CR, CReq, CRL, CRh, PR, or HI	Up to approximately 4 years
Secondary	Duration of remission (DOR)	For AML, the time from first CR/CRi/CRh/PR response to the first documentation of disease progression, start of new anticancer therapy, or death due to any cause. For MDS, the time from first CR (or Req)/CRL/CRh/PR to the first documentation of disease progression, start of new anticancer therapy, or death due to any cause	Up to approximately 4 years
Secondary	Overall survival (OS)	Time from start of study treatment to the date of death due to any cause	Up to approximately 4 years
Secondary	Event-free survival (EFS)	Time from first dose to the first documentation of progression, failure to achieve remission within 6 months of study entry, disease relapse, or death due to any cause, whichever comes first.	Up to approximately 4 years
Secondary	Progression-free survival (PFS)	Time from first dose to the first documentation of progression, disease relapse, or death from any cause, whichever comes first	Up to approximately 4 years
Secondary	MRD-negative ORR	Proportion of participants with AML or MDS who achieve MRD-negative ORR	Up to approximately 4 years
Secondary	Time to response (TTR)	Time from start of study treatment to the first documentation of objective response	Up to approximately 4 years
Secondary	Rate of conversion to transfusion independence (TI)	Proportion of participants who convert from transfusion dependence at baseline to TI post-baseline	Up to approximately 4 years
Secondary	Rate of TI maintenance	Proportion of participants who were TI at baseline and maintain TI post-baseline	Up to approximately 4 years