Safety and Tolerability of Combined Treatment With Nilotinib and Ruxolitinib in CML and Ph+ ALL Patients

Chronic Myeloid Leukemia Clinical Trial

— CoRNea  

Official title:

A Phase Ib Single-arm, Open-label, Multicenter Study to Assess the Safety and Tolerability of Combined Treatment With Nilotinib 300mg BID and Ruxolitinib Increasing Dose in CML and Ph+ ALL Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02253277
• Other study ID #: CAMN107YDE19
• Status: Completed
• Phase: Phase 1
• Start date: February 18, 2015
• Est. completion date: April 3, 2018

Study information

• Verified date: April 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In this study it was the rationale to evaluate the safety and tolerability of the combined administration of nilotinib and increasing dose of ruxolitinib in patients with chronic myeloid leukemia and patients with Philadelphia positive acute lymphoblastic leukemia.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: April 3, 2018
• Est. primary completion date: March 6, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Patients of the first stratum must have chronic myeloid leukemia receiving nilotinib first-line therapy or receiving second-line or subsequent-line treatment with nilotinib.

Patients of the second stratum must have CML in AP/BC or relapsed/refractory Ph+ ALL, or be Ph+ ALL patients with MRD with or without prior nilotinib pretreatment;

Patients must have adequate end organ function, as defined by:

• Creatinine < 2.0 x upper limit of normal (ULN)

• Total bilirubin < 1.5 x ULN (< 3.0 x ULN if related to disease or polymorphism, such as Mb. Gilbert)

• ALT and AST < 2.5 x ULN (< 5.0 x ULN if related to disease)

• Serum lipase = 1.5 x ULN

• Alkaline phosphatase = 2.5 x ULN (< 5.0 x ULN if related to disease);

Patients must have the following electrolyte values within normal limits or corrected to within normal limits with supplements prior to the first dose of study medication:

• Potassium

• Magnesium

• Phosphate

• Total calcium (corrected for serum albumin);

Female patients of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days before initiation of study drug. All WOCBP must use highly effective contraceptive methods throughout and during 3 months after study;

Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of = 1 for patients in CP, = 2 for patients in AP/BC or with relapsed/refractory Ph+ ALL or with Ph+ ALL with MRD;

Patient has the following laboratory values within 7 days of starting study drug:

• For CML and Ph+ ALL patients: platelet count > 75 x 109/L and ANC > 1.0 x 109/L

Exclusion Criteria:

Patient must not have evidence of active malignancy other than the existing CML or ALL

Patient must not receive drugs that interfere with coagulation or inhibits platelet function, with the exception of aspirin = 150 mg per day or low molecular weight heparin.

Patient must not have history of platelet dysfunction, bleeding diathesis, and/or coagulopathy in the 6 months prior to screening;

Patient must not require treatment with any strong CYP3A4 inducer or inhibitor

Patient must not have history of hypersensitivity to any of the study drugs or to drugs of similar chemical classes and their excipients;

Patients must not take other investigational drugs within 28 days prior to screening;

Patient must not be pregnant or lactating at screening and/or baseline;

Patient must not have impaired cardiac functions

Other protocol-defined inclusion/exclusion criteria may apply

Related Conditions & MeSH terms

• Chronic Myeloid Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Intervention

Drug:
• Nilotinib
Nilotinib was supplied by Novartis as 150 mg and 200 mg hard gelatin capsules. Nilotinib was not dosed by weight or body surface area. Medication labels were in German and complied with the legal requirements of Germany. They included storage conditions for the drug but no information about the patient. The investigator emphasized compliance and instructed the patient to take nilotinib exactly as prescribed.
• Ruxolitinib
Ruxolitinib was supplied by Novartis as 5 mg, 15 mg, and 20 mg tablets. Medication labels were in German and complied with the legal requirements of Germany. They included storage conditions for the drug but no information about the patient. The investigator emphasized compliance and instructed the patient to take ruxolitinib exactly as prescribed.

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Jena
Germany	Novartis Investigative Site	Leipzig

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of dose limiting toxicities (DLTs)	Occurrence of DLTs during cycle 1	Baseline, up to day 28 (equals first cycle)
Secondary	Safety and tolerability profile of nilotinib and ruxolitinib administered in combination	Maximum Tolerated Dose (MTD) and/or Recommended Phase II Dose (RPIID) of ruxolitinib in combination with nilotinib. (timeframe, baseline up to month 12)	Baseline, up to month 12
Secondary	Trough levels of nilotinib and ruxolitinib administered in combination	Trough levels will be determined by measuring the minimum plasma concentration (Cmin).	Baseline, up to month 12
Secondary	Clinical activity of nilotinib and ruxolitinib administered in combination	Chronic myeloid leukemia in chronic phase: assessment of molecular response: MMR (=0.1% BCR-ABL) and MR4 (=0.001% BCR-ABL) at 3, 6, 12 months; Advanced disease: assessment of cytogenetic response will be based on evaluating percentage of Ph+ metaphases	Baseline and at 3, 6, and 12 months