Flotetuzumab for Relapsed Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) Following Allogeneic Hematopoietic Cell Transplantation (Allo-HCT)

NCT04582864 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2020111225P50CA171963
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators hypothesize that flotetuzumab for relapsed AML following allo-HCT will be safe, tolerable and may facilitate preferential immune effector cell retargeting of leukemic cells resulting in improved patient outcomes. Furthermore, administration of a donor lymphocyte infusion (DLI) (if available) in combination with flotetuzumab will be safe, tolerable and may provide additional therapeutic efficacy.

Conditions

Relapsed Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Efficacy as Measured by Number of Participants With CR(Mrd), CR, and CRi

  * Complete remission without minimal residual disease (CRmrd): CR with negativity for a genetic marker by RT-qPCR, or CR with negativity by MFC * Complete remission (CR): Bone marrow blasts \<5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC ≥1.0 × 10\^9/L (1000/µL); platelet count ≥100 × 10\^9/L (100,000/µL), transfusion independence * CR with incomplete hematologic recovery (CRi): All CR criteria except for residual neutropenia (\<1.0 × 10\^9/L \[1000/µL\]) or thrombocytopenia (\<100 × 10\^9/L \[100,000/µL\])

  At the end of Cycle 1 (each cycle is 28 days)

Secondary Outcomes (12)

• Efficacy as Measured by Number of Participants With CR and CRi

  At the end of Cycle 2 (each cycle is 28 days)

• Overall Response Rate

  At the end of Cycle 2 (each cycle is 28 days)

• Morphologic Leukemia-free State (MLFS) Rate

  At the end of Cycle 2 (each cycle is 28 days)

• Partial Remission (PR) Rate

  At the end of Cycle 2 (each cycle is 28 days)

• Stable Disease (SD) Rate

  At the end of Cycle 2 (each cycle is 28 days)

Study Arms (1)

Flotetuzumab

EXPERIMENTAL

* Will start on cycle 1 day 1 on the dose escalation ramp schedule of flotetuzumab as a continuous intravenous (IV) infusion. Patients will be initiated at 30 ng/kg/day and have their dose increased daily to a target goal of 500 ng/kg/day by day 7 * Patients will continue on flotetuzumab at 500 ng/kg/day for the remaining 21 days of the 28 day cycle. * On cycle 1 day 28, patients will undergo bone marrow biopsy for assessment of disease status. Patients who have achieved a CR/CRi will proceed to a second cycle per protocol, while patients with a PR or SD or better may proceed to cycle 2 with permission of the investigator. Patients with available donor lymphocytes may receive DLI concurrently with flotetuzumab during Cycle 1 and/or Cycle 2.

Drug: Flotetuzumab; Procedure: Donor lymphocyte infusion

Interventions

Flotetuzumab DRUG

Will be provided by MacroGenics Inc.

Also known as: MGD006

Flotetuzumab

Donor lymphocyte infusion PROCEDURE

DLI represents a non-specific form of adoptive cell therapy which involves infusion of a pool of allogeneic immune cells, including CD4+ T cells, CD8+ T cells, regulatory T cells (T Regs), natural killer (NK) cells and professional antigen presenting cells.

Also known as: DLI

Flotetuzumab

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed relapsed acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), including any AML subtype, except acute promyelocytic leukemia (APL), and including AML that has evolved from a previous MDS or MPN.
• Patients must have peripheral blast count ≤ 20,000/mm3. Use of hydroxyurea to control blast count is permitted.
• Patients must be status post allo-HCT (including: matched related, matched unrelated, haploidentical, mismatched unrelated; and cord blood HCT).
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2
• Adequate organ function, defined as:
• Hepatic transaminase (both alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels ≤2.5 times the institutional upper limit of normal (ULN),
• Total bilirubin level ≤1.5 times the ULN (unless the patient has a history of Gilbert's Syndrome, in which case, total bilirubin must be ≤2.5 times the ULN),
• Creatinine clearance of ≥50 ml/min
• Adequate organ reserve including cardiovascular (ejection fraction within institutional normal limits), pulmonary (baseline pulmonary function test \[PFT\]: carbon monoxide diffusion capacity in the lung \[DLCO\] \> 50%, forced expiratory volume in 1 second \[FEV1\] \> 70%), renal, and hepatic functioning sufficient, in the judgment of the Investigator, to undergo therapy.
• Normal thyroid function or stable thyroid tests on supplementation, except euthyroid sick syndrome.
• Recovery from toxicities of clinical consequence attributed to previous chemotherapy to CTCAE v4.0 Grade ≤ 1 (i.e., certain toxicities such as alopecia will not be considered in this category).
• Female patients of childbearing potential must test negative for pregnancy at enrollment and during the study. Sexually active women of child-bearing potential, unless surgically sterile, must be willing to use a highly effective method of birth control defined as those which result in a low failure rate (i.e., less than 1% per year) such as implants, injectables, combined oral contraceptives, intra-uterine devices (IUDs) or vasectomized partner. Male patients with partners of childbearing potential must be either vasectomized or agree to use a condom in addition to having their partners use another method of contraception resulting in a highly effective method of birth control defined as those which result in a low failure rate (i.e., less than 1% per year) such as implants, injectables, combined oral contraceptives, or IUDs. Patients should not have sexual intercourse with females who are either pregnant or lactating without a condom. Contraception should be employed from the time of consent through 12 weeks after MGD006 administration. Patients should also abstain from sperm/egg donation during the course of the study.
• Able to have corticosteroids weaned to ≤0.5mg/kg prednisone/day (or equivalent)
• Able to have non-steroidal immunosuppression discontinued, including:
• mycophenolate (MMF)

You may not qualify if:

• Active GVHD requiring systemic immunosuppression with more than 0.5 mg/day prednisone
• Currently receiving any other investigational agents.
• Any active untreated autoimmune disorders (with the exception of vitiligo, resolved childhood atopic dermatitis, prior Grave's disease now euthyroid clinically and with stable supplementation).
• Second primary malignancy that requires active therapy (adjuvant hormonal therapy is allowed).
• Antitumor therapy (chemotherapy, radiotherapy, antibody therapy, molecular- targeted therapy, retinoid therapy, or investigational agent) within 5 half-lives of Cycle 1 Day 1
• At the time of study entry, steroids \>0.5mg/kg of prednisone or equivalent (except steroid inhaler, nasal spray or ophthalmic solution which are allowed).
• Use of immunosuppressant medications (other than steroids as noted) in the 2 weeks prior to study drug administration (Cycle 1 Day 1).
• Isolated extramedullary relapse (i.e., no evidence of bone marrow involvement).
• Known central nervous system (CNS) leukemia. Patients with suspected CNS leukemia must be evaluated by lumbar puncture and be free of CNS disease prior to study entry. Previously treated CNS leukemia is allowed provided adequate treatment has been provided and the patient is free of CNS disease.
• Any medical or psychiatric condition limiting full compliance or increasing the safety risk, at the discretion of the PI, such as:
• active uncontrolled infection (including, but not limited to viral, bacterial, fungal, or mycobacterial infection),
• known human immunodeficiency virus infection,
• known, active, or chronic hepatitis B or C infection (appropriately treated HBV/HCV infections with documented clearance of viral titer are allowed),
• Grade 3 or 4 bleeding,
• significant pulmonary compromise including chronic supplemental oxygen use, history of non-infectious pneumonitis (including radiation pneumonitis), pulmonary fibrosis, or severe chronic obstructive pulmonary disease (COPD),

Sponsors & Collaborators

• Washington University School of Medicine: lead
• MacroGenics: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Matthew Christopher
• Organization: Washington University School of Medicine

christopherm@wustl.edu

314-273-0286

Study Officials

• Matthew Christopher, M.D., Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2020
• First Posted: October 12, 2020
• Study Start: May 20, 2021
• Primary Completion: March 29, 2024
• Study Completion: July 26, 2024
• Last Updated: December 6, 2024
• Results First Posted: December 6, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Time Frame: From 2 years to 10 years after accrual closure
• Access Criteria: IPD will be shared in de-identified form with investigators whose proposed use of the data has been approved by an independent review committee for that purpose.

Locations

US (1)