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A Phase II, Single Arm, Open Label Study of Treatment-free Remission After Achieving Sustained MR4.5 on Nilotinib (ENESTop)


Phase 2
N/A
N/A
Open (Enrolling)
Both
Chronic Myeloid Leukemia

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Trial Information

A Phase II, Single Arm, Open Label Study of Treatment-free Remission After Achieving Sustained MR4.5 on Nilotinib (ENESTop)


Inclusion Criteria:



1. Male or female patients >= 18 years of age

2. ECOG Performance Status of 0, 1, or 2

3. Patient with diagnosis of BCR-ABL positive CML

4. Patient has received a minimum of 3 years of tyrosine kinase inhibitor treatment
(first with imatinib and then switched to nilotinib) since initial diagnosis

5. Patient has at least 2 years of nilotinib treatment prior to study entry.

6. Patient has achieved MR4.5 (local laboratory assessment) during nilotinib treatment,
and determined by a Novartis designated central PCR lab assessment at screening

7. Adequate end organ function as defined by:

- Direct bilirubin ≤ 15umol/L

- SGOT(AST) and SGPT(ALT) < 3 x ULN (upper limit of normal)

- Serum lipase ≤ 2 x ULN

- Alkaline phosphatase ≤ 2.5 x ULN

- Serum creatinine < 1.5 x ULN

8. Patients must have the following electrolyte values ≥ LLN (lower limit of normal)
limits or corrected to within normal limits with supplements prior to the first dose
of study medication:

- Potassium

- Magnesium

- Total calcium (corrected for serum albumin)

9. Patients must have normal marrow function as defined below:

- Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L

- Platelets ≥ 100 x 109/L

- Hemoglobin ≥ 9.0 g/dL

10. Written informed consent obtained prior to any screening procedures

Exclusion Criteria:

1. Prior AP, BC or allo-transplant

2. Patient has documented MR4.5 at the time when switched from imatinib to nilotinib

3. Patients with known atypical transcript

4. Mutation(s) detected if a testing was done in the past (there is no requirement to
perform mutation testing at study entry if it was not done in the past)

5. Dose reductions due to neutropenia or thrombocytopenia in the past 6 months

6. Patient ever attempted to permanently discontinue imatinib or nilotinib treatment

7. Known impaired cardiac function including any one of the following:

- Inability to determine the QT interval on ECG

- Complete left bundle branch block

- 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

- QTcF > 480 msec

- History or clinical signs of myocardial infarction within 1 year prior to study
entry

- History of unstable angina within 1 year prior to study entry

- Other clinically significant heart disease (e.g. uncontrolled congestive heart
failure or uncontrolled hypertension)

8. 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 (defined as HbA1c > 9%), uncontrolled infection)

9. History of acute pancreatitis within 1 year prior to study entry or past medical
history of chronic pancreatitis

10. Known presence of a significant congenital or acquired bleeding disorder unrelated to
cancer

11. History of other active malignancy within 5 years prior to study entry with the
exception of previous or concomitant basal cell skin cancer, previous cervical
carcinoma in situ treated curatively

12. Patients who have not recovered from prior surgery

13. Treatment with other investigational agents (defined as not used in accordance with
the approved indication) within 4 weeks of Day 1

14. 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 study entry. See Appendix 14.1 for a list of these medications. This list
may not be comprehensive.

15. 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 study entry. These herbal medicines may
include Echinacea, (including E. purpurea, E. angustifolia and E. pallida), Piperine,
Artemisinin, St. John's Wort, and Ginkgo.

16. 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 study entry. (Please see
www.azcert.org/medical-pros/drug-lists/printable-drug-list.cfm for a list of agents
that prolong the QT interval.)

17. 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)

18. 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.

19. Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using effective methods of contraception during
dosing of study treatment. Effective contraception methods include:

- 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 and documented by follow up hormone level
assessment

- Male sterilization (at least 6 months prior to screening). For female patients
on the study, study participation assumes the vasectomized male partner is the
sole partner for that patient

- Barrier methods of contraception: condom or occlusive cap (diaphragm or
cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository

- 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) 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 is suspected of 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.

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Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

No documented confirmed loss of MR4, no documented loss of MMR and no re-starting of nilotinib therapy

Outcome Description:

Proportion of patients without confirmed loss of MR4 or loss of MMR within 12 months following nilotinib TFR is calculated by dividing the number of patients with no documented confirmed loss of MR4, no documented loss of MMR and no re-starting of nilotinib therapy in the first 12 months after starting nilotinib TFR phase by the number of patients who entered nilotinib TFR phase.

Outcome Time Frame:

First 12 months following nilotinib cessation.

Safety Issue:

No

Principal Investigator

Novartis Pharmaceuticals

Investigator Role:

Study Director

Investigator Affiliation:

Novartis Pharmaceuticals

Authority:

United States: Food and Drug Administration

Study ID:

CAMN107A2408

NCT ID:

NCT01698905

Start Date:

December 2012

Completion Date:

July 2018

Related Keywords:

  • Chronic Myeloid Leukemia
  • Phase II, single arm, open label, nilotinib, treatment-free remission, MR4.5, confirmed loss of MR4, loss of MMR, Ph+ CML-CP
  • Leukemia
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Name

Location

USC/Kenneth Norris Comprehensive Cancer Center USCLos Angeles, California  90033
St. Agnes Hospital SCBaltimore, Maryland  21229
City of Hope National Medical Center Dept of OncologyDuarte, California  91010-3000
Indiana Blood and Marrow Institute SCBeach Grove, Indiana  46107
Compass OncologyVancouver, Washington  98683