A Study Evaluating Venetoclax Alone and in Combination With Azacitidine in Participants With Relapsed/Refractory Myelodysplastic Syndromes (MDS)

AbbVie

Status and phase: Completed; Phase 1

Conditions: Myelodysplastic Syndromes (MDS)

Treatments: Drug: azacitidine; Drug: venetoclax

Study type: Interventional

Funder types: Industry; Other

Identifiers

NCT02966782

2016-001904-46 (EudraCT Number)

M15-522

Details and patient eligibility

About

This is a Phase 1b, open-label, multicenter study designed to evaluate the safety and pharmacokinetics of venetoclax as a single-agent and in combination with azacitidine in participants with relapsed/refractory Myelodysplastic Syndromes (MDS).

Enrollment: 70 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Subjects who have relapsed or refractory MDS.

• Subject enrolled in venetoclax monotherapy must have documented failure of prior therapy with a hypomethylating agent (HMA). HMA-failure is defined as:

  1. Relapse after initial complete or partial response or hematological improvement after at least 4 cycles of azacitidine or at least 4 cycles of decitabine within the last 5 years, OR
  2. Failure to achieve complete or partial response or hematological improvement after at least 4 cycles of azacitidine or at least 4 cycles of decitabine within the last 5 years

• Subjects must have presence of < 20% bone marrow blasts per bone marrow biopsy/aspirate at screening.

• Subject is not a candidate to undergo allogenic hematopoietic stem cell transplantation (HSCT).

• Subject must have an Eastern Cooperative Oncology Group (ECOG) performance score of ≤2.

• Subject must have adequate hematologic, renal, and hepatic function.

Exclusion criteria

• Subject has received prior therapy with a BH3 mimetic.
• Subject has MDS evolving from a pre-existing myeloproliferative neoplasm (MPN).
• Subject has MDS/MPN including chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (CML), juvenile myelomonocytic leukemia (JMML) and unclassifiable MDS/MPN.
• Subject has received allogeneic HSCT or solid organ transplantation.
• Subject has received a live attenuated vaccine within 4 weeks prior to the first dose of study drug.
• Subject is pregnant or breastfeeding.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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70 participants in 3 patient groups

Venetoclax monotherapy (Cohort 1)

Experimental group

Treatment:

Drug: venetoclax

Venetoclax + azacitidine (Cohort 2)

Experimental group

Treatment:

Drug: venetoclax

Drug: azacitidine

Safety Expansion (Cohort 3)

Experimental group

Treatment:

Drug: venetoclax

Drug: azacitidine