← Back to Search

Tyrosine Kinase Inhibitor

Nilotinib Treatment-Free Remission for Chronic Myeloid Leukemia (ENESTfreedom Trial)

Phase 2

Waitlist Available

Research Sponsored by Novartis Pharmaceuticals

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Minimum of 2 calendar years of nilotinib treatment with at least the last 12 months of nilotinib treatment prior to pre-screening at approved total daily dose of 600 mg BID or at a reduced dose of 400 mg QD if required from the perspective of tolerance for BCR-ABL positive CML in documented chronic phase at the time of diagnosis

Evidence of typical BCR-ABL transcripts (b3a2 and/or b2a2) at the time of CML-CP diagnosis i.e. prior to first start of TKI treatment which are amenable to standardized RT-PCR quantification

Must not have

Impaired cardiac function including any one of the following: LVEF < 45% or below the institutional lower limit of the normal range (whichever is higher), Inability to determine the QT interval on ECG, except for patients with evidence of measurable QT interval at the time of CML diagnosis (e.g. prior to first start of TKI treatment) and who have no documented clinical signs of cardiovascular disease and/or clinical signs of conduction abnormality, Complete left bundle branch block, Right bundle branch block plus left anterior or posterior hemiblock, Use of a ventricular-paced pacemaker, Congenital long QT syndrome or a known family history of long QT syndrome, History of or presence of clinically significant ventricular or atrial tachyarrhythmias, Clinically significant resting bradycardia, QTc > 450 msec on the average of three serial baseline ECG (using the QTcF formula). If QTcF > 450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-tested for QTc. This exclusion criterion is not applicable for patients with non-measurable QT interval who have evidence of measurable QT interval at the time of CML diagnosis (e.g. prior to first start of TKI treatment) and who have no documented clinical signs of cardiovascular disease and/or clinical signs of conduction abnormality, History or clinical signs of myocardial infarction within 1 year of study entry, History of unstable angina within 1 year of study entry, Other clinically significant heart disease (e.g. congestive heart failure, cardiomyopathy or uncontrolled hypertension), History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis, Known presence of significant congenital or acquired bleeding disorder unrelated to cancer, Severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol (e.g. uncontrolled diabetes, uncontrolled infection), History of another active malignancy within 5 years prior to study entry with the exception of previous or concomitant basal cell skin cancer and previous carcinoma in situ treated curatively, Treatment with other investigational agents (defined as not used in accordance with the approved indication) within 4 weeks of Day 1, Patients who have not recovered from prior surgery, Patients actively receiving therapy with strong CYP3A4 inhibitors and/or inducers, and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug, Patients actively receiving therapy with herbal medicines that are strong CYP3A4 inhibitors and/or inducers, and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug. These herbal medicines may include Echinacea, (including E. purpurea, E. angustifolia and E. pallida), Piperine, Artemisinin, St. John's Wort, and Ginkgo, Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either safely discontinued or switched to a different medication prior to starting study drug, Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, or gastric bypass surgery), Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test, Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during the study and for 14 days after the final dose of nilotinib. Highly effective contraception is defined as either: Total abstinence (when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception, Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment, Male sterilization (at least 6 months prior to enrolling). For female patients on the study the vasectomized male partner should be the sole partner for that patient, Use of a combination of any two of the following: Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception, Placement of an intrauterine device (IUD) or intrauterine system (IUS), Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository, In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to enrolling. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential, If a study patient becomes pregnant or suspects being pregnant during the study or within 30 days after the final dose of nilotinib, the Study Doctor needs to be informed immediately and ongoing study treatment with nilotinib has to be stopped immediately.

Previous treatment with BCR-ABL inhibitors other than nilotinib for more than a total cumulative duration of 4 weeks

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 48, 96, 144, 192, 264 weeks, end of 6, 7, 8, 9 and 10 years

Awards & highlights

No Placebo-Only Group

Summary

This trial looked at whether patients with a specific type of leukemia could safely stop taking a certain medication without the leukemia coming back.

Who is the study for?

Adults diagnosed with chronic phase Chronic Myeloid Leukemia (CML) who have been treated with nilotinib for at least two years and are in deep molecular response. They must have normal organ and marrow function, no history of pancreatitis or uncontrolled diabetes, not be pregnant or breastfeeding, and cannot be on certain medications that affect liver enzymes or prolong the QT interval.

What is being tested?

The trial is testing if patients with CML who respond well to nilotinib can safely stop treatment without the disease coming back. Participants will first receive nilotinib until they achieve a specific level of response before attempting a treatment-free period.

What are the potential side effects?

Nilotinib may cause side effects such as rash, nausea, headache, fatigue, itching, vomiting, diarrhea, coughing up blood; it can also affect blood sugar levels and heart rhythm.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I have been treated with nilotinib for my CML for at least 2 years, including the last 12 months.

Select...

My CML was confirmed with specific genetic markers before starting TKI treatment.

Select...

I am able to get out of my bed or chair and move around.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have been treated with BCR-ABL inhibitors, other than nilotinib, for over 4 weeks.

Select...

I have been treated with alpha-interferon before.

Select...

My chronic myeloid leukemia has returned after worsening.

Select...

My diabetes is not well-managed, with an HbA1c level over 9%.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 48, 96, 144, 192, 264 weeks, end of 6, 7, 8, 9 and 10 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~48, 96, 144, 192, 264 weeks, end of 6, 7, 8, 9 and 10 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 48, 96, 144, 192, 264 weeks, end of 6, 7, 8, 9 and 10 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Percentage of Patients Who Are in MMR (Major Molecular Response) at 48 Weeks After Starting the Treatment-free Remission (TFR) Phase

Secondary study objectives

Duration of Re-initiated Treatment Required to Regain MMR After Loss of MMR

Duration of Re-initiated Treatment Required to Regain MR4.5 After Loss of MMR

Kinetics of BCR-ABL Transcript After Re-start of Nilotinib Therapy

+12 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Nilotinib followed by treatment-freeExperimental Treatment1 Intervention

Patients who received a minimum of 2 years of first line nilotinib treatment and with pre-screen PCR results in ≥ MR4.5 entered the consolidation phase of the study (52 weeks - nilotinib 300 mg BID). Patients with Minimal Residual Disease (MRD) at the end of this phase entered the Treatment-Free Remission (TFR) phase where no treatment was given. Non eligible patients will enter the continuation phase of the study. Patients with MRD at the end of the continuation phase will enter the TFR-2 phase of the study where no treatment is given. Non eligible patients will enter the prolonged continuation phase of the study. If at any time during TFR or TFR-2 the patient loses MMR, nilotinib treatment will be immediately re-initiated (nilotinib 300 mg BID).

0 / 8Eligibility criteria met