Study of the Safety and Efficacy of Gemtuzumab Ozogamicin (GO) and Venetoclax in Patients With Relapsed or Refractory CD33+ Acute Myeloid Leukemia:Big Ten Cancer Research Consortium BTCRC-AML17-113

NCT04070768 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: BTCRC-AML17-113
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 4

Brief Summary

This is a Phase Ib Study to determine the Maximum Tolerated Dose (MTD) of Venetoclax in combination with Gemtuzumab Ozogamicin(GO) in subjects with relapsed/refractory acute myeloid leukemia. Using a standard 3+3 design, subjects will receive once cycle of combination therapy. After one cycle of combination therapy, subjects showing response will continue on to one cycle of consolidation therapy with GO\\Veneoclax. Subjects who respond to combination therapy will continue on maintenance Venetoclax until progression or unacceptable toxicity. Dose-limiting toxicity, defined as an adverse event related (possible, probably, or definite) to Venetoclax and/or Gemtuzumab fulfilling one of the following criteria: criteria:

• Hematologic toxicity: treatment-related grade 3 or worse neutropenia and/or thrombocytopenia due to bone marrow hypocellularity present at the end of cycle one (day 28) with an additional 28 days allowed for count recovery (i.e. present at day 56); specifically grade 3 or worse neutropenia or thrombocytopenia with the bone marrow documented to be free of leukemic infiltration. Note: patients who enter the study with grade 3 or worse cytopenias will not be evaluable for hematologic dose-limiting toxicities.
• Non-hematologic toxicity: any grade 3 or worse treatment-related toxicity occurring within the first cycle (excluding grade 3-4 infections during cycle one). The study will also evaluate the Overall Response Rate, Anti-leukemic activity, Relapse-free Survival (RFS), event-free survival (EFS) , and overall survival (OS). The study will evaluate quality of life using the European Organization for the Research and Treatment of Cancer 30 item questionnaire (EORTC QLQ-C30).

Conditions

Acute Myeloid Leukemia

Keywords

relapsed; refractory; CD33+

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Venetoclax When Administered With Gemtuzumab Ozogamicin (GO)

  MTD was determined by testing increasing doses up to 600mg orally daily on dose escalation cohorts 1 to 3 with 3 to 6 participants each. MTD reflects the highest dose of drug where fewer than 33% of subjects experience a dose limiting toxicity (DLT). DLT is defined as an adverse event related (possible, probably, or definite) to Venetoclax and/or Gemtuzumab fulfilling one of the following criteria: Hematologic toxicity: treatment-related grade 3 or worse neutropenia and/or thrombocytopenia due to bone marrow hypocellularity present at the end of cycle one (day 28) with an additional 28 days allowed for count recovery (i.e. present at day 56); Note: patients who enter the study with grade 3 or worse cytopenias will not be evaluable for hematologic DLT. Non-hematologic toxicity: any grade 3 or worse treatment-related toxicity occurring within the first 56 days.

  42 days

Secondary Outcomes (5)

• Overall Response Rate

  Up to 7 months

• Anti-leukemic Activity Rate

  Up to 7 months

• Relapse-free Survival

  Up to 7 months

• Event-free Survival

  7 months

• Overall Survival (OS)

  Up to 8 months

Study Arms (1)

Gemtuzumab Ozogamicin(GO) + Venetoclax

EXPERIMENTAL

Gemtuzumab Ozogamicin(GO) + Venetoclax

Drug: Gemtuzumab Ozogamicin; Drug: Venetoclax

Interventions

Gemtuzumab Ozogamicin DRUG

Gemtuzumab Ozogamicin 3mg/m\^2, Days 1,4,7

Also known as: GO

Gemtuzumab Ozogamicin(GO) + Venetoclax

Venetoclax DRUG

Venetoclax, 100,200,400, or 600mg Daily Dose

Gemtuzumab Ozogamicin(GO) + Venetoclax

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Ages 18 to 75 years at the time of consent.
• ECOG Performance Status of 0-2 within 7 days prior to registration; see Appendix I.
• Patients must have AML, as defined, that is relapsed or refractory. Prior therapy including chemotherapy, immunotherapy, biological or targeted therapy (e.g. FMS-like tyrosine kinase-3 (FLT3) inhibitors, other kinase inhibitors, azacitidine, ATRA) is allowed.
• CD33 expression (by flow or IHC) in at least 20% of the leukemia blasts per local pathologist.
• Prior cancer treatment must be completed at least 21 days prior to registration and the subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to ≤Grade 1 or baseline.
• Demonstrate adequate organ function as defined in the table in the protocol; all screening labs to be obtained within 28 days prior to registration.
• Females of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to registration. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months
• Females of childbearing potential and males must be willing to use effective contraception during treatment and for at least 30 days after the last dose of Venetoclax. Females will be advised to use effective contraception for at least 6 months after the last dose of Gemtuzumab and males for at least 3 months after the last dose of Gemtuzumab.
• As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study

You may not qualify if:

• Subjects meeting any of the criteria below may not participate in the study:
• Patients with history of prior use of GO or Venetoclax NOTE: Starting with dose cohort 3, prior therapy with venetoclax is allowed, provided patients do not have evidence of p53 deletion or mutations. If the dose cohort is de-escalated to dose cohort 2 due to toxicity in cohort 3, prior exposure to venetoclax will continue to be allowed, provided patients do not have evidence of p53 deletion/mutations.
• History of myeloproliferative neoplasm \[MPN\] including myelofibrosis, essential thrombocythemia, polycythemia vera, CML with or without BCR-ABL1 translocation, and AML with BCR-ABL1 translocation.
• More than three lines of prior therapy. A line of therapy consists of ≥1 complete cycle of a single agent, a regimen consisting of a combination of several drugs, or a planned sequential therapy of various regimens (e.g., 3-6 cycles of initial therapy with bortezomib-dexamethasone \[VD\] followed by stem cell transplantation \[SCT\], consolidation, and lenalidomide maintenance is considered 1 line).
• WBC \>25 × 109/L. Cytoreduction is required (hydroxyurea as per local standard of care).
• Acute promyelocytic leukemia.
• Unresolved ≥grade 2 clinically significant nonhematologic toxicities from prior anticancer therapy or unresolved disseminated intravascular coagulation ≥ grade 2 per CTCAE v5 criteria.
• History of other malignancies within 1 year prior to study entry, with the exception of: adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast; basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; previous malignancy confined and surgically resected (or treated with other modalities), with curative intent.
• Investigational drug within 4 weeks of study entry.
• History of CHF requiring treatment, left ventricular ejection fraction ≤ 50%, cardiac insufficiency grade III or IV per New York Heart Association classification (NYHA; see Appendix II), or chronic stable angina
• Patients who are HIV positive.
• Known CNS involvement with AML.
• Previous hematopoietic stem cell transplant within 2 months.
• Previous history of veno-occlusive disease/sinusoidal obstruction syndrome.
• Patients who are positive for hepatitis B or C infection with the exception of those with an undetectable viral load within 3 months. Subjects with serologic evidence of prior vaccination to HBV \[i.e., HBs Ag-, and anti-HBs+\] may participate.

Sponsors & Collaborators

• John Quigley: lead
• Pfizer: collaborator
• AbbVie: collaborator

Study Sites (4)

Univeristy of Illinois

Chicago, Illinois, 60612, United States

Location

Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Indianapolis, Indiana, 46202, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Recurrence

Interventions

Gemtuzumab; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Fauzia Sharmin
• Organization: Hoosier Cancer Research Network

fsharmin@hoosiercancer.org

317-921-2050

Study Officials

• John Quigley, MD

  University of Illinois at Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: August 26, 2019
• First Posted: August 28, 2019
• Study Start: September 6, 2019
• Primary Completion: October 12, 2023
• Study Completion: February 20, 2024
• Last Updated: May 4, 2025
• Results First Posted: May 4, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)