Clinical Trials /

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

NCT04050280

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: CLAG-GO for Patients With Persistent, Relapsed or Refractory AML
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: 1946GCCC
  • NCT ID: NCT04050280

Conditions

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

Interventions

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

Purpose

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.
    

Trial Arms

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

Eligibility Criteria

        Inclusion Criteria:

          1. 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.

          2. 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.

          3. Eastern Cooperative Oncology Group performance status of 0-2.

          4. 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.

          5. At least 20% expression of CD33 as determined by flow cytometry or immunohistochemical
             staining.

          6. Adequate renal function, defined as a serum creatinine less than 1.8 mg/dL.

          7. 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.

          8. 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.

          9. 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.

         10. 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.

         11. Ability to give written informed consent.

        Exclusion Criteria:

          1. Patients with acute promyelocytic leukemia (FAB-M3) or chronic myelogenous leukemia in
             blast phase.

          2. Isolated myeloid sarcoma. Patients must have marrow involvement with AML to enter the
             study.

          3. Patients with known active AML involvement of the central nervous system.

          4. Prior treatment with gemtuzumab ozogamicin or cladribine for AML. Prior treatment with
             cytarabine is permitted.

          5. As patients will be receiving G-CSF prior to chemotherapy, patients presenting with
             symptomatic leukostasis (as judged by the investigator) are excluded. Hydroxyurea,
             6-mercaptopurine and/or leukapheresis for blast count control (see inclusion criterion
             #4) for patients with asymptomatic hyperleukocytosis is permitted before starting
             treatment, but must be stopped for at least 24 hours prior to starting protocol
             treatment.

          6. Active uncontrolled infection. Patients on prophylactic antibacterial, antifungal,
             and/or antiviral agents and patients whose infections are controlled with these agents
             are eligible.

          7. Known active hepatitis B or C or other known active hepatic disorder.

          8. Any history of veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS).

          9. 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.

         10. 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response Rate (Efficacy)
Time Frame:Responses will be assessed following induction chemotherapy, within 14 days of documented full blood count recovery.
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:Presence of minimal residual disease
Time Frame:Assessed at the end of induction, consolidation and maintenance therapy, up to 1 year
Safety Issue:
Description:This is determined by flow cytometry completed through Hematologics, Inc.
Measure:Time to relapse or death
Time Frame: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.
Safety Issue:
Description:Time to relapse is measured from the date of confirmed remission until the date of confirmed relapse. Time to death (survival) is measured from the date of enrollment until the date of death, assessed up to 2 years.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Maryland, Baltimore

Last Updated

March 30, 2020