Fractionated Gemtuzumab Ozogamicin Followed by Non-engraftment Donor Leukocyte Infusions for Relapsed/Refractory Acute Myeloid Leukemia

NCT03374332 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: BrUOG 345
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

This study includes patients with relapsed acute leukemia who have previously been treated with standard treatment that is still present and there is no curative treatment option available. Researchers are studying whether the drug Gemtuzumab Ozogamicin, followed by an infusion of blood cells called leukocytes from a donor, can stimulate the immune system to potentially fight the leukemia. Gemtuzmab ozogamicin is a class of drugs known as an antibody drug conjugate. The drug is given on days 1,4,7. It is infused, attaches to cells with a certain marker on the surface (the majority of which would be leukemia cells). The drug is then internalized and the chemotherapy drug becomes activated. Gemtuzumab is currently FDA approved for the treatment of acute myeloid leukemia. The infusion of leukocytes to stimulate the immune system to fight your leukemia is investigational and has not been proven to cure cancer. This combination of Gemtuzumab Ozogamicin and donor leukocytes is not an FDA approved treatment and is investigational. Initially a total of 6 patients will be included in the study to assess the safety of the treatment. Once 6 patients have been treated and no unacceptable toxicities are seen, more patients will be enrolled. The study will treat up to 18 patients on the study.

Conditions

Acute Myeloid Leukemia

Keywords

Refractory; progression; recurrence

Outcome Measures

Primary Outcomes (2)

• Phase 1: Determine the RP2D or MTD of Nonengraftment Donor Leukocyte Infusions With Fractionated Gemtuzumab Ozogamicin in Patients With Relapsed/Refractory AML Defined as Dose Level Without Dose Limiting Toxicities.

  The MTD of non-engraftment donor leukocyte infusions administered with fractionated gemtuzumab ozogamicin in patients with relapsed/refractory AML is determined by the dose level achieved with no Dose limiting toxicities. Measure = participants without DLTs. The recommended phase 2 dose (RP2D) or maximum tolerated dose (MTD) was evaluated by utilizing a 3+3 design to determine if 1-2x108 CD3 cells/kg can be safely administered with fractionated Gemtuzumab Ozogamicin administered on days 1,4 and 7 (total dose capped at 13.5 mg). The leukocyte infusion is administered on day 8 after completion of GO day 7. Two DLI dose levels well be assessed: DLI Dose Level 1: 1-2x107 CD3+ cells/kg DLI Dose Level 2: 1-2x108 CD3+ cells/kg The RP2D/MTD is determined by the dose level achieved with no Dose limiting toxicities. Measure = participants without DLTs through 35 days post DLI.

  35 days post infusion

• Response Rate

  Response rate of infusional gemtuzumab ozogamicin followed by nonengraftment donor leukocyte infusions in patients with refractory acute myeloid leukemia. Bone Marrow Biopsy to be done in patients thought to have responded. Complete remission or complete remission with incomplete count recovery, after one cycle of treatment. Rationale for including CRi: CRi has previously been used in gemtuzumab ozogamicin trials because of incomplete platelet recovery seen with this drug.

  4 weeks post infusion

Secondary Outcomes (3)

• Number of Participants Reaching 24 Months Progression Free Survival

  Through 2 years post end of treatment

• Number of Participants Who Met the Objective for Overall Survival at 2 Years

  Through 2 years post end of treatment

• Number of Participants With Dose Limiting Toxicities as Defined by the Protocol

  Start of treatment through 30 days post the final infusion

Study Arms (3)

Phase 1 Treatment 1: Gemtuzumab Ozogamicin and DLI Dose Level 1

EXPERIMENTAL

Day 8: The product will be administered unprocessed on day 8 (same day as leukapheresis) with a minimum of 1x10\^7 CD3+ cells and maximum of 2x10\^7 CD3+ cells/kg irrespective of the number of CD34+ cells. Patients who show a transient response to therapy can receive up to two additional donor leukocyte infusions with GO 6mg/m2 (2mg/m2 each day, capped at 4.5mg) for all patients regardless of age administered on days 1,4, and 7, no sooner than 35 days status post their last cellular infusion.

Drug: Gemtuzumab Ozogamicin (GO); Other: Donor Leukocytes

Phase 1 Treatment 2: Gemtuzumab Ozogamicin and DLI Dose Level 2

EXPERIMENTAL

Day 8: The product will be administered unprocessed on day 8 (same day as leukapheresis) with a minimum of 1x10\^8 CD3+ cells and maximum of 2x10\^8 CD3+ cells/kg irrespective of the number of CD34+ cells. Patients who show a transient response to therapy can receive up to two additional donor leukocyte infusions with GO 6mg/m2 (2mg/m2 each day, capped at 4.5mg) for all patients regardless of age administered on days 1,4, and 7, no sooner than 35 days status post their last cellular infusion.

Drug: Gemtuzumab Ozogamicin (GO); Other: Donor Leukocytes

Phase 2 Treatment 3: Gemtuzumab Ozogamicin and DLI Dose Level (MTD determined from Phase1)

EXPERIMENTAL

Maximum Tolerated Dose (MTD) determined from Phase 1 portion of study Day 8: The product will be administered unprocessed on day 8 (same day as leukapheresis) with a dose of 1x10\^7 - 2x10\^7 CD3+ cells OR 1x10\^8 - 2x10\^8 CD3+ cells/kg irrespective of the number of CD34+ cells. MTD AS DETERMINED BY PHASE 1 Patients who show a transient response to therapy can receive up to two additional donor leukocyte infusions with GO 6mg/m2 (2mg/m2 each day, capped at 4.5mg) for all patients regardless of age administered on days 1,4, and 7, no sooner than 35 days status post their last cellular infusion.

Drug: Gemtuzumab Ozogamicin (GO); Other: Donor Leukocytes

Interventions

Gemtuzumab Ozogamicin (GO) DRUG

Patients will be given gemtuzumab ozogamicin on days 1,4, and 7. Capped at 4.5mg individual doses. Total doses capped at 13.5mg.

Also known as: Mylotarg

Phase 1 Treatment 1: Gemtuzumab Ozogamicin and DLI Dose Level 1; Phase 1 Treatment 2: Gemtuzumab Ozogamicin and DLI Dose Level 2; Phase 2 Treatment 3: Gemtuzumab Ozogamicin and DLI Dose Level (MTD determined from Phase1)

Donor Leukocytes OTHER

The product will be administered unprocessed on day 8/24 hours post GO (same day as leukapheresis) with a minimum of CD3+ cells and maximum of CD3+ cells/kg irrespective of the number of CD34+ cells.

Phase 1 Treatment 1: Gemtuzumab Ozogamicin and DLI Dose Level 1; Phase 1 Treatment 2: Gemtuzumab Ozogamicin and DLI Dose Level 2; Phase 2 Treatment 3: Gemtuzumab Ozogamicin and DLI Dose Level (MTD determined from Phase1)

Eligibility Criteria

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

You may qualify if:

• Histologic confirmation of acute myeloid leukemia (AML)
• Recurrence or progression (including refractory disease) of AML after at least 1 prior standard treatment with progression within 6 months from last treatment.
• No curative treatment option is available
• ≥ 4-weeks since prior chemotherapy or radiation to cellular therapy infusion.
• Age equal to or greater than 18 years.
• Patients with a history of invasive second malignancy who are disease free for ≥ 2 years.
• Patients must have an expected life expectancy of at least 2 months at the time of initiation of treatment
• No active systemic infections allowed.

You may not qualify if:

• DLCO ≥ 40% with no symptomatic pulmonary disease.
• LVEF ≥ 40% by MUGA or echocardiogram.
• Creatinine \<1.5x ULN or any serum creatinine level associated with a measured or calculated creatinine clearance of \>40 mL/min, AST and ALT \< 2.5x ULN, Total Bilirubin \< 1.5 x ULN
• Women of childbearing potential and sexually active males must use 2 forms of effective contraception method from time of consent through 6 months after completing treatment (whether last treatment is infusion or drug).
• Not pregnant or nursing. Women of child bearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 7 days prior to beginning of treatment (drug). Post-menopausal women (surgical menopause or lack of menses ≥12 months) do not need to have a pregnancy test, please document status.
• Performance status ≤ 2 (or KPS 70)
• Evidence of HIV infection.
• Any uncontrolled severe, concurrent illness which in the opinion of the treating physician would make this protocol treatment unreasonably hazardous for the patient.
• Oxygen dependent obstructive pulmonary disease.
• Failure to demonstrate adequate compliance with medical therapy and follow-up
• Significant medical or psychiatric illness that would impair the ability to participate in protocol therapy.
• Previous allogeneic stem cell transplant
• Patients who have had previous purine analog (fludarabine, pentostatin, 2-CDA) treatment or treatment with alemtuzumab within 1 year of entering the study
• Previous history of Veno-occlusive disease/Sinusoidal Obstruction Syndrome
• Active hepatitis B or C

Sponsors & Collaborators

• The Miriam Hospital: collaborator
• Pfizer: collaborator
• Brown University: lead
• Rhode Island Hospital: collaborator

Study Sites (1)

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Disease Progression; Recurrence

Interventions

Gemtuzumab

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: John Reagan, MD
• Organization: Brown University Oncology Research Group (BrUOG)

BrUOG@brown.edu

401-863-3000

Study Officials

• John Reagan, MD

  Brown University Oncology Research Group (BrUOG)

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2017
• First Posted: December 15, 2017
• Study Start: December 31, 2019
• Primary Completion: September 26, 2023
• Study Completion: March 31, 2025
• Last Updated: July 23, 2026
• Results First Posted: July 23, 2026

Record last verified: 2026-06

Locations

US (1)