NCT04050280

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

A Phase II Study of Cladribine, Cytarabine, and Granulocyte-Colony Stimulating Factor With Fractionated Gemtuzumab Ozogamicin (CLAG-GO) for the Treatment of Patients With Persistent, Relapsed or Refractory Acute Myeloid Leukemia

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 39 (estimated)
• Sponsor: University of Maryland, Baltimore · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

This is a single-arm, two-stage phase II trial of cladribine, cytarabine, granulocyte colony stimulating factor and gemtuzumab ozogamicin (CLAG-GO) in adult patients with acute myeloid leukemia (AML) who are either have persistent disease after initial induction chemotherapy or are in first relapse, with early stopping for unacceptable toxicity. The trial will be conducted at the University of Maryland Greenebaum Comprehensive Cancer Center (UMGCCC), with a target enrollment of 39 patients if the trial proceeds to the second stage. Eligible patients will receive induction chemotherapy with CLAG-GO at the doses detailed below. In the first stage of the trial, a sequential boundary is used to monitor induction mortality and halt accrual if this mortality is significantly above 10%. If more than 6 responses are seen in the initial 19 patients, 20 additional patients will be enrolled in the 2nd stage. Responders may proceed to allogeneic hematopoietic stem cell transplantation (alloHSCT) at any time after induction, and these patients will be monitored for at least 30 days post-transplantation for veno-occlusive disease. Responding patients will also have the option of having a single cycle of consolidation therapy using the same CLAG-GO regimen, followed by maintenance with GO monotherapy for up to 8 additional cycles. Responses will be categorized according to the European LeukemiaNet (ELN) response criteria for AML. Assessment of measureable residual disease (MRD) will be conducted with bone marrow aspirate samples and changes in immunophenotype will be evaluated. In addition, single nucleotide polymorphism (SNP) analysis and sialylation status of CD33, along with sialidase activity of myeloblasts will be evaluated and correlated with responses and survival times. Safety and toxicity will be evaluated continuously, and event-free survival, and overall survival as well as the proportion of patients proceeding to receive alloHSCT will be estimated.

Conditions

• Acute Myeloid Leukemia, Adult
• Acute Myeloid Leukemia Recurrent
• Acute Myeloid Leukemia, Relapsed, Adult

Interventions

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

Timeline

• Start date: 2019-11-01
• Primary completion: 2026-06-30
• Completion: 2027-02-01
• First posted: 2019-08-08
• Last updated: 2025-05-01

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study