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

  • End date
    Oct 22, 2023
  • participants needed
  • sponsor
    John Quigley
Updated on 22 July 2022
flow cytometry
consolidation therapy
refractory acute myeloid leukemia (aml)
blast cells


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:

  • 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).

Condition Acute Myeloid Leukemia
Treatment gemtuzumab ozogamicin, venetoclax
Clinical Study IdentifierNCT04070768
SponsorJohn Quigley
Last Modified on22 July 2022


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Inclusion Criteria

Subjects must meet all of the following applicable inclusion criteria to participate in
Ages 18 to 75 years at the time of consent
this study
Written informed consent and HIPAA authorization for release of personal health
information. NOTE: HIPAA authorization may be included in the informed consent or
ECOG Performance Status of 0-2 within 7 days prior to registration; see Appendix I
obtained separately
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
CD33 expression (by flow or IHC) in at least 20% of the leukemia blasts per local
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

Exclusion Criteria

Subjects meeting any of the criteria below may not participate in the study
Acute promyelocytic leukemia
Investigational drug within 4 weeks of study entry
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
Unable or unwilling to undergo a screening bone marrow study
Patients with history of prior use of GO or Venetoclax NOTE: Starting with dose cohort
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
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
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 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
Active uncontrolled infection or severe systemic infection. Enrollment is possible
after control of infection, at discretion of the treating physician
Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the
mother is being treated on study)
Patients who have received strong and/or moderate CYP3A inducers or inhibitors within
days prior to the initiation of study treatment unless deemed necessary by the
treating physician. (See protocol)
Patients who have consumed grapefruit, grapefruit products, Seville oranges (including
marmalade containing Seville oranges) or Starfruit within 3 days prior to the
initiation of study treatment
Malabsorption syndrome or other condition that precludes enteral route of
Psychological, familial, sociological, or geographical condition that would preclude
study compliance and follow-up
Other severe acute or chronic medical or psychiatric condition, or laboratory
abnormality that may increase the risk associated with study participation or
investigational product administration or may interfere with the interpretation of
study results and, in the judgment of the investigator, would make the patient
inappropriate for enrollment in this study
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