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

  • STATUS
    Recruiting
  • End date
    Oct 24, 2022
  • participants needed
    24
  • sponsor
    John Quigley
Updated on 24 November 2020
cancer
tyrosine
flow cytometry
tretinoin
consolidation therapy
azacitidine
refractory acute myeloid leukemia (aml)
gemtuzumab
blast cells
venetoclax

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:

  • Hematologic toxicity: treatment-related grade 4 or worse bone marrow hypocellularity present at the end of cycle one (day 28); specifically grade 4 cytopenias (anemia, neutropenia and/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 (excluding grade 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).

Details
Treatment gemtuzumab ozogamicin, venetoclax
Clinical Study IdentifierNCT04070768
SponsorJohn Quigley
Last Modified on24 November 2020

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Eligibility

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Inclusion Criteria

Is your age greater than or equal to 18 yrs?
Gender: Male or Female
Do you have any of these conditions: Acute myeloid leukemia or Acute Myelogenous Leukemia (AML)?
Do you have any of these conditions: acute myeloblastic leukemia or anll or acute myelogenous leukemia or Acute myeloid leukemia or Acute Myelogenous Leukemia (AML)?
Do you have any of these conditions: acute myelogenous leukemia or acute myeloblastic leukemia or anll or Acute Myelogenous Leukemia (AML) or Acute myeloid leukemia?
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
Patients must have AML, as defined,28 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 cytometry, assessed as CD33 expression in at least 20% of the leukemia blasts per local pathologist.29
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 protocol
Females of childbearing potential must have a negative serum 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

Patients with history of prior use of GO or Venetoclax
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 two lines of prior therapy
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), 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
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 7 days prior to the initiation of study treatment. (See Appendix III)
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 administration
Psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up
Unable or unwilling to undergo a screening bone marrow study
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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