Pracinostat and Gemtuzumab Ozogamicin (PraGO) in Patients With Relapsed/Refractory Acute Myeloid Leukemia

NCT03848754 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: PRO 33922
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, single-center phase 1 clinical study aimed at determining the maximum-tolerated dose and safety of the combination of gemtuzumab ozogamicin (GO) and pracinostat (P) in patients with relapsed/refractory acute myeloid leukemia.

Conditions

Relapsed Adult AML

Keywords

acute myeloid leukemia

Outcome Measures

Primary Outcomes (1)

• The number of subjects experiencing a dose-limiting toxicity.

  Maximum-tolerated (MTD) dose of pracinostat in combination with fixed dose GO induction will be determined by the 3+3 design rules. If there are no dose-limiting toxicities (DLTs) in the first three patients, the dose of pracinostat will be escalated to 60mg. Escalation to the next dose level will be done only after the third patient on the previous dose level has been observed for 28 days, and no DLTs were noticed. If there is 1 DLT, an additional 3 patients will be tested at same dose level. If there are ≥ 2 DLTs in three or six patients, the study will be placed on hold. If there is \< 2 DLTs in the first three or six patients, the dose of pracinostat will be escalated to 60mg. If there are no DLTs in the first three patients at 60mg, an additional three patients will be enrolled to ensure six patients are treated at the MTD.

  First 28-day cycle

Secondary Outcomes (6)

• Number of subjects surviving at six months.

  6 Months

• Number of subjects progression free at 6 months.

  6 Months

• The number of subjects with a complete response.

  Day 28

• The number of subjects with complete response with incomplete count recovery (CRi).

  Day 28

• The number of subjects with partial remission (PR).

  Day 28

Study Arms (4)

Pracinostat 45 mg with Gemtuzumab Ozogamicin

EXPERIMENTAL

* Gemtuzumab Ozogamicin Induction: GO 3 mg/m\^2 on Day 1, 4, and 7 * Pracinostat Induction: 45 mg administered orally 3 days a week with 48 hours between dosing for 3 consecutive weeks, followed by 1 week of rest, in 28-day cycles. We will utilize a 3+3 design to determine the safe dose of pracinostat in combination with fixed dose GO. If there are no DLTs in the first three patients, the dose of pracinostat will be escalated to 60mg. Escalation to the next dose level will be done only after the third patient on the previous dose level has been observed for 28 days, and no DLTs were noticed. If there is 1 DLT, an additional 3 patients will be tested at same dose level. If there are ≥ 2 DLTs in 3 or 6 patients, the study will be placed on hold. If there is \< 2 DLTs in the first 3 or 6 patients, the dose of pracinostat will be escalated to 60mg. If there are no DLTs in the first 3 patients at 60 mg, an additional 3 patients will be enrolled to ensure 6 patients are treated at the MTD.

Drug: Gemtuzumab Ozogamicin 3 mg/m^2; Drug: Pracinostat - 45 mg

Pracinostat 60 mg with Gemtuzumab Ozogamicin

EXPERIMENTAL

* Gemtuzumab Ozogamicin Induction: GO 3 mg/m\^2 on Day 1, 4, and 7 * Pracinostat: 60 mg administered orally 3 days a week with 48 hours between dosing for 3 consecutive weeks, followed by 1 week of rest, in 28-day cycles. We will utilize a 3+3 design to determine the safe dose of pracinostat in combination with fixed dose GO. If there are no DLTs in the first three patients, the dose of pracinostat will be escalated to 60mg. Escalation to the next dose level will be done only after the third patient on the previous dose level has been observed for 28 days, and no DLTs were noticed. If there is 1 DLT, an additional 3 patients will be tested at same dose level. If there are ≥ 2 DLTs in 3 or 6 patients, the study will be placed on hold. If there is \< 2 DLTs in the first 3 or 6 patients, the dose of pracinostat will be escalated to 60mg. If there are no DLTs in the first 3 patients at 60 mg, an additional 3 patients will be enrolled to ensure 6 patients are treated at the MTD.

Drug: Gemtuzumab Ozogamicin 3 mg/m^2; Drug: Pracinostat - 60 mg

Gemtuzumab Ozogamicin Monotherapy Maintenance

EXPERIMENTAL

Response will be assessed through bone marrow biopsy on Day 28. Patients achieving at least a partial remission marrow will be offered up to 5 cycles of maintenance therapy. Maintenance should begin no later than 42 days after initial induction. \*\*Gemtuzumab Ozogamicin Maintenance: 2 mg/m\^2 intravenous administration on day 1, in a 28-day cycle.

Drug: Gemtuzumab Ozogamicin 2 mg/m^2

Pracinostat with Gemtuzumab Ozogamicin Maintenance

EXPERIMENTAL

Response will be assessed through bone marrow biopsy on Day 28. Patients achieving at least a partial remission marrow will be offered up to 5 cycles of maintenance therapy. Maintenance should begin no later than 42 days after initial induction. * Gemtuzumab Ozogamicin Maintenance: 2 mg/m\^2 intravenous administration on day 1, in a 28-day cycle. * Pracinostat Maintenance: (In addition to GO, only if induction dose escalation occurs) 45 mg orally 3 days a week with 48 hours between dosing, for three consecutive weeks, followed by 1 week of rest, in a 28-day cycle.

Drug: Gemtuzumab Ozogamicin 2 mg/m^2; Drug: Pracinostat - 45 mg

Interventions

Gemtuzumab Ozogamicin 3 mg/m^2 DRUG

GO 3 mg/m\^2 on Day 1, 4, and 7 Maintenance: 2mg/m2 intravenous administration on day 1, in a 28-day cycle.

Also known as: Mylotarg

Pracinostat 45 mg with Gemtuzumab Ozogamicin; Pracinostat 60 mg with Gemtuzumab Ozogamicin

Gemtuzumab Ozogamicin 2 mg/m^2 DRUG

GO 2 mg/m\^2 on Day 1 of a 28-day cycle.

Also known as: Mylotarg

Gemtuzumab Ozogamicin Monotherapy Maintenance; Pracinostat with Gemtuzumab Ozogamicin Maintenance

Pracinostat - 45 mg DRUG

Induction: 45mg administered orally 3 days a week with 48 hours between dosing (e.g., Monday, Wednesday, and Friday) for three consecutive weeks, followed by 1 week of rest, in 28-day cycles.

Pracinostat 45 mg with Gemtuzumab Ozogamicin; Pracinostat with Gemtuzumab Ozogamicin Maintenance

Pracinostat - 60 mg DRUG

Escalation: 60 mg administered orally three days a week with 48 hours between dosing (e.g., Monday, Wednesday, and Friday) for three consecutive weeks, followed by one week of rest, in 28-day cycles.

Pracinostat 60 mg with Gemtuzumab Ozogamicin

Eligibility Criteria

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

You may qualify if:

• Morphologically documented AML or secondary AML \[from prior conditions such as myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN)\] or therapy related AML (t-AML), as defined by World Health Organization (WHO) criteria.
• Age ≥60 years, with relapsed/refractory AML to at least one line of therapy. Patients with antecedent MDS who progressed to AML while on hypomethylating agent therapy will also be eligible.
• Age 18-59 years with relapsed/refractory AML to at least two lines of intensive induction chemotherapy, or one line of therapy if deemed unsuitable for further intensive chemotherapy.
• Patients aged 18 years or older with relapsed AML after allogeneic hematopoietic cell transplantation, if deemed unsuitable for further intensive chemotherapy.
• Detectable CD33 expression on AML blasts confirmed by flow cytometry.
• Karnofsky performance status ≥ 60 (or Eastern Cooperative Oncology Group (ECOG) Performance Score (PS) of 2 or less).
• Adequate organ system function as outlined below:
• Total bilirubin ≤ 2 x upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN.
• Serum creatinine ≤ 2 or a serum creatinine clearance ≤ 1.5 x ULN.
• Baseline EKG with QT-interval corrected (QTcF) ≤ 450ms.
• Females should be using adequate contraception, should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child-bearing potential. Male patient should avoid impregnating a female partner.
• It is not known what effects this treatment has on human pregnancy or development of the embryo or fetus. Therefore, female patients participating in this study should avoid becoming pregnant, and male patients should avoid impregnating a female partner. Non-sterilized female patients of reproductive age and male patients should use effective methods of contraception through defined periods during and after study treatment as specified below.
• Female patients must meet one of the following:
• Postmenopausal for at least one year before the screening visit, or
• Surgically sterile, or

You may not qualify if:

• Acute promyelocytic leukemia (APL).
• Prior chemotherapy, radiotherapy, or investigative agent within 14 days, or within five half-lives of study entry.
• Subjects must have recovered from side effects of prior treatment.
• The use of hydroxyurea for leukoreduction prior to start of dosing is permitted.
• Hematopoietic Stem Cell Transplantation (HCT) within 60 days of enrollment, or evidence of veno-occlusive disease (VOD) at any time post-transplant, or active graft-versus-host disease requiring systemic immunosuppressive therapy.
• Life-threatening illness unrelated to AML, or any serious medical or psychiatric illness that could potentially interfere with participation in this study.
• Active and uncontrolled human immunodeficiency virus (HIV), or chronic Hepatitis B, or Hepatitis C.

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Froedtert Hospital & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Gemtuzumab; SB939 compound

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

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

Study Officials

• Sameem Abedin, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: February 19, 2019
• First Posted: February 21, 2019
• Study Start: May 24, 2019
• Primary Completion: May 5, 2021
• Study Completion: May 5, 2021
• Last Updated: June 30, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)