CLAG-GO for Patients With Persistent, Relapsed or Refractory AML

NCT04050280 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 1946GCCC ; HP-00085334
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

This study involves evaluating a combination of chemotherapy drugs known as "CLAG-GO" \[cladribine, cytarabine, granulocyte-colony stimulating factor (G-CSF) and gemtuzumab ozogamicin (GO)\] in the treatment of acute myeloid leukemia (AML) that has not responded well to standard therapy or has returned after an initial remission (relapsed). The trial will be conducted at the University of Maryland Greenebaum Comprehensive Cancer Center (UMGCCC). Potential participants will go through a screening period to see if they are eligible to join the study. If eligible, participants will be hospitalized for 4-5 weeks to receive study treatment with CLAG-GO, called induction chemotherapy. If tests show that the cancer is in remission after induction chemotherapy, participants may undergo further chemotherapy (known as consolidation) or may proceed with bone marrow/stem cell transplantation. Patients who receive consolidation chemotherapy and remain in remission may have up to 8 cycles of outpatient maintenance therapy. A cycle lasts about 28 days. All participants will be monitored carefully for both side effects and to see if the study treatment is working. Lab tests and exams will be conducted throughout the entire study. In addition, special studies will be done at various time points to try to understand better how the drugs work and which patients are likely to respond best.

Conditions

Acute Myeloid Leukemia, Adult; Acute Myeloid Leukemia Recurrent; Acute Myeloid Leukemia, Relapsed, Adult

Outcome Measures

Primary Outcomes (2)

• Response Rate (Efficacy)

  Responses will be judged according to modified European LeukemiaNet recommendations published in 2017. Patients who achieve either 1) complete remission without minimal residual disease, 2) complete remission, or 3) complete remission with incomplete hematologic recovery will be considered responders

  Responses will be assessed following induction chemotherapy, within 14 days of documented full blood count recovery.

• Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)

  All adverse events will be graded according to CTCAE version 5.

  From date of enrollment until death from any cause, whichever comes first, assessed up to 1 year.

Secondary Outcomes (2)

• Presence of minimal residual disease

  Assessed at the end of induction, consolidation and maintenance therapy, up to 1 year

• Time to relapse or death

  measured from the date of confirmed remission until the date of confirmed relapse, assessed up to 2 years. Time to death (survival) is measured from the date of enrollment until the date of death, assessed up to 2 years.

Study Arms (1)

CLAG-GO

EXPERIMENTAL

Cladribine, Cytarabine, and Granulocyte-Colony Stimulating Factor with Fractionated Gemtuzumab Ozogamicin (CLAG-GO)

Drug: Cladribine, Cytarabine, and Granulocyte-Colony Stimulating Factor with Fractionated Gemtuzumab Ozogamicin (CLAG-GO)

Interventions

Cladribine, Cytarabine, and Granulocyte-Colony Stimulating Factor with Fractionated Gemtuzumab Ozogamicin (CLAG-GO) DRUG

Induction: G-CSF 300 mcg subcutaneously daily on days 0-5. Cladribine 5 mg/m2 in normal saline given intravenously over 2 hours daily on days 1-5. Cytarabine 2000 mg/m2 in normal saline given intravenously over 4 hours daily on days 1-5. Gemtuzumab ozogamicin 3 mg/m2 intravenously over 2 hours on days 1 and 4, prior to cladribine and cytarabine. Consolidation: If CRMRD-, CR or CRi is confirmed by bone marrow biopsy and aspirate after induction chemotherapy, patients may receive one cycle of consolidation chemotherapy (at the discretion of the investigator) with the same CLAG-GO regimen at the same doses given for induction. In addition, the investigator has the option of giving CLAG alone without GO if there is concern for increased risk of sinusoidal obstruction syndrome. Patients who remain in CRMRD-, CR or CRi after consolidation chemotherapy may receive up to eight infusions of GO 2 mg/m2 approximately every 28 days.

Also known as: Mylotarg

CLAG-GO

Eligibility Criteria

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

You may qualify if:

• Adult patients age 18 years or older, with a pathologically confirmed diagnosis of AML \[excluding acute promyelocytic leukemia (APL)\] according to WHO criteria. AML may be de novo, or following a prior hematologic disease and/or therapy-related.
• Patients must have relapsed after or be refractory to at least one course of an intensive chemotherapy regimen, for example anthracycline/cytarabine ("7+3" or daunorubicin and cytarabine liposome). Patients with residual disease on day 13-22 of initial induction chemotherapy are eligible, provided the bone marrow cellularity is ≥ 30% AND bone marrow blasts are ≥ 20%. Hypomethylating agents such as azacitidine or decitabine are allowed as a prior therapy, but are not considered an intensive chemotherapy regimen.
• Eastern Cooperative Oncology Group performance status of 0-2.
• Any systemic chemotherapy and any radiotherapy must be completed at least 7 days prior to initiation of protocol therapy, with the exception of hydroxyurea or 6-mercaptopurine for cytoreduction.
• At least 20% expression of CD33 as determined by flow cytometry or immunohistochemical staining.
• Adequate renal function, defined as a serum creatinine less than 1.8 mg/dL.
• Adequate hepatic function, defined as a direct bilirubin less than 2 times the institutional upper limit of normal (ULN) and AST, ALT and Alkaline Phosphatase less than 3 times the ULN.
• Patients who relapse after allogeneic hematopoietic stem cell transplantation are eligible, provided they are at least 60 days from stem cell infusion, do not have \> grade 1 graft versus host disease, and have been off all immunosuppressive therapy for at least 2 weeks.
• Female patients of childbearing potential must have a negative pregnancy test and agree to use an adequate method of contraception as defined by the protocol. This must persist through the treatment period until at least 6 months after the last dose of chemotherapy or GO.
• Male subjects who are able to father children and are having intercourse with females of childbearing potential must also agree to an acceptable method of contraception through the treatment period until at least 3 months after the last dose of chemotherapy or GO, and must refrain from sperm donation during this period.
• Ability to give written informed consent.

You may not qualify if:

• Patients with acute promyelocytic leukemia (FAB-M3) or chronic myelogenous leukemia in blast phase.
• Isolated myeloid sarcoma. Patients must have marrow involvement with AML to enter the study.
• Patients with known active AML involvement of the central nervous system.
• Prior treatment with gemtuzumab ozogamicin or cladribine for AML. Prior treatment with cytarabine is permitted.
• Active uncontrolled infection. Patients on prophylactic antibacterial, antifungal, and/or antiviral agents and patients whose infections are controlled with these agents are eligible.
• Known active hepatitis B or C or other known active hepatic disorder.
• Any history of veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS).
• Active concurrent malignancy, unless disease-free for at least 3 years. Subjects with treated non-melanoma skin cancer, in situ carcinoma or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed. Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease are eligible if hormonal therapy has been initiated or the malignancy has been treated surgically or with definitive radiotherapy.
• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that per investigator's judgment would limit compliance with study requirements.

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• Hematologics, Inc: collaborator

Study Sites (1)

University of Maryland Greenebaumn Comprehensive Cancer Center

Baltimore, Maryland, 21201, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Recurrence

Interventions

Cladribine; Cytarabine; Granulocyte Colony-Stimulating Factor; 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)

2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxyadenosines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Calicheamicins; Aminoglycosides; Glycosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins

Study Officials

• Vu H. Duong, MD, MS

  University of Maryland Greenebaumn Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Veronica Kflu

CONTACT

410-328-9416; veronica.kflu@umm.edu

Oyinkansola Arasanmi

CONTACT

410-328-6635; Oyinkansola.Arasanmi@umm.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: July 16, 2019
• First Posted: August 8, 2019
• Study Start: November 1, 2019
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): February 1, 2027
• Last Updated: May 1, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)