A Pharmacokinetic (PK) Study of Nilotinib in Pediatric Patients With Philadelphia Chromosome-positive (Ph+) Chronic Myelogenous Leukemia (CML) or Acute Lymphoblastic Leukemia (ALL)

NCT01077544 | Completed Phase 1 Results DMC

• 2 other identifiers: CAMN107A21202010-018419-14
• Study Type: interventional
• Target: 15
• Locations: 4 countries
• Sites: 12

Brief Summary

This study will assess the pharmacokinetics of nilotinib in Ph+ CML pediatric patients that are newly diagnosed or resistant or intolerant to imatinib or dasatinib or refractory or relapsed Ph+ ALL compared to the adult populations. It will also evaluate safety and activity of nilotinib as secondary objectives.

Conditions

Chronic Myeloid Leukemia; Acute Lymphoblastic Leukemia

Keywords

Chronic Myeloid Leukemia; Acute Lymphoblastic Leukemia; Ph+ CML; Ph+ ALL; pediatric; nilotinib; imatinib; chronic phase; accelerated phase; newly diagnosed Ph+ CML; dasatinib

Outcome Measures

Primary Outcomes (7)

• Summary of Nilotinib Non-compartmental PK Parameters: Cmax

  The full PK profiles of nilotinib in pediatric patients were assessed using serial sampling following a single 230 mg/m2 dose on Cycle 1 Day 1.

  Cycle 1 Day 1

• Summary of Nilotinib Non-compartmental PK Parameters: Tmax

  The full PK profiles of nilotinib in pediatric patients were assessed using serial sampling following a single 230 mg/m2 dose on Cycle 1 Day 1.

  Cycle 1 Day 1

• Summary of Nilotinib Non-compartmental PK Parameters: AUClast (Last = 24h)

  The full PK profiles of nilotinib in pediatric patients were assessed using serial sampling following a single 230 mg/m2 dose on Cycle 1 Day 1.

  Cycle 1 Day 1

• Summary of Nilotinib Non-compartmental PK Parameters: AUC0-12h

  The full PK profiles of nilotinib in pediatric patients were assessed using serial sampling following a single 230 mg/m2 dose on Cycle 1 Day 1.

  Cycle 1 Day 1

• Summary of Nilotinib Steady-state PK Parameters: AUCss

  The steady-state PK profiles of nilotinib in pediatric patients were estimated using trough sampling following multiple 230 mg/m2 bid doses

  Cycle 1 Day 8 - Cycle 1 Day 28

• Summary of Nilotinib Steady-state PK Parameters: CLF (Body Surface Area (BSA) Adjusted)

  The steady-state PK profiles of nilotinib in pediatric patients were estimated using trough sampling following multiple 230 mg/m2 bid doses

  Cycle 1 Day 8 - Cycle 1 day 28

• Summary of Nilotinib Steady-state PK Parameters: Cmin

  The full PK profiles of nilotinib in pediatric patients were assessed using serial sampling following a single 230 mg/m2 dose.

  Cycle 1 Day 8 - Cycle 1 Day 28

Secondary Outcomes (4)

• Number of Ph+ CML Participants With Confirmed Complete Hematologic Response (CHR)

  minimum of 12 cycles (28 days per cycle)

• Number of Ph+ CML Participants With Cytogenic Response

  minimum of 12 cycles (28 days per cycle)

• Number of Ph+ CML Participants With Major Molecular Response (MMR)

  minimum of 12 cycles (28 days per cycle)

• Efficacy Endpoints for Ph+ ALL Patients

  minimum of 12 cycles (28 days per cycle)

Study Arms (2)

Group 1

EXPERIMENTAL

1 year to \< 10 years pediatric patients with newly diagnosed CP-Ph+ CML, or CP or AP-Ph+ CML resistant/intolerant to imatinib and/or dasatinib, or relapsed/refractory Ph+ ALL (acute lymphoblastic leukemia) treated at the proposed dose of 230 mg/m2 bid.

Drug: Nilotinib

Group 2

EXPERIMENTAL

\>= 10 years to \<18 years pediatric patients with newly diagnosed CP-Ph+ CML, or CP or AP-Ph+ CML resistant/intolerant to imatinib and/or dasatinib, or relapsed/refractory Ph+ ALL (acute lymphoblastic leukemia) treated at the proposed dose of 230 mg/m2 bid.

Drug: Nilotinib

Interventions

Nilotinib DRUG

Nilotinib capsules were delivered in bottles with dose strengths of 50mg, 150mg and 200mg. Patients were administered nilotinib 230 mg/m2 (per BSA) bid, orally, rounded to the nearest 50 mg (max single dose 400 mg) for 28 days (1 cycle) for up to 12 cycles prior to protocol amendment 3 and up to 24 cycles post amendment 3. Capsules were to be swallowed whole with water. Apple sauce (puréed apple) may have been used as a vehicle for dosing where capsules were not able to be swallowed whole with water.

Also known as: AMN107

Group 1; Group 2

Eligibility Criteria

• Age: 1 Year - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Must have one of the following: newly diagnosed CP Ph+CML, CP or AP resistant/ intolerant to imatinib and/or dasatinib, or Ph+ ALL either relapsed after or refractory to standard therapy
• adequate renal, hepatic and pancreatic function

You may not qualify if:

• patients receiving therapy with strong CYP3A4 inhibitors and/or inducers and treatments cannot be stopped or changed to a different medication at least 14 days prior to starting study drug
• patients receiving therapy with any medications with a known risk or possible risk to prolong the QT interval and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug.
• gastrointestinal impairment or disease that may interfere with drug absorption
• liver, pancreatic or severe renal disease unrelated to disease under study
• impaired cardiac function
• patients who received dasatinib within 3 days of starting study drug
• patients who received imatinib within 5 days of starting study drug
• patients receiving hydroxyurea or corticosteroids that has not been discontinued at least 1 week after initiation of nilotinib
• patients who received hematopoietic growth factors within 7 days of starting study drug or Pegfilgrastim (Neulasta®) within 14 days of starting study drug
• patients with Stem Cell Transplant (SCT) or Rescue without TBI: Evidence of active graft vs. host disease and \< 3 months since SCT

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (12)

Novartis Investigative Site

Bordeaux, Aquitaine, 33076, France

Location

Novartis Investigative Site

Lille, 59037, France

Location

Novartis Investigative Site

Paris, 75571, France

Location

Novartis Investigative Site

Poitiers, 86021, France

Location

Novartis Investigative Site

Monza, MB, 20900, Italy

Location

Novartis Investigative Site

Padua, PD, 35128, Italy

Location

Novartis Investigative Site

Roma, RM, 00161, Italy

Location

Novartis Investigative Site

Amsterdam, 1081 HV, Netherlands

Location

Novartis Investigative Site

Rotterdam, 3015 CN, Netherlands

Location

Novartis Investigative Site

West Midlands, Birmingham, B4 6NH, United Kingdom

Location

Novartis Investigative Site

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Novartis Investigative Site

Bristol, BS2 8BJ, United Kingdom

Location

Related Links

• Results for CAMN107A2120 can be found on the Novartis Clinical Trial Results Website

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

nilotinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

trialandresults.registries@novartis.com

82-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2010
• First Posted: March 1, 2010
• Study Start: April 14, 2011
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: December 29, 2020
• Results First Posted: January 27, 2016

Record last verified: 2020-10

Locations

GB (3); IT (3); FR (4); NL (2)