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Trial record 1 of 1 for:    NCT02253277
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Safety and Tolerability of Combined Treatment With Nilotinib and Ruxolitinib in CML and Ph+ ALL Patients (CoRNea)

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ClinicalTrials.gov Identifier: NCT02253277
Recruitment Status : Completed
First Posted : October 1, 2014
Last Update Posted : May 1, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief 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.

Condition or disease Intervention/treatment Phase
Chronic Myeloid Leukemia Drug: Nilotinib Drug: Ruxolitinib Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : February 18, 2015
Actual Primary Completion Date : March 6, 2018
Actual Study Completion Date : April 3, 2018


Arm Intervention/treatment
Experimental: Nilotinib and Ruxolitinib
The study included two strata, which were to be treated in parallel. The first stratum consisted of CML-patients in CP, which had been on nilotinib treatment before entering the study. These patients did not optimally respond to the previous treatment. The second stratum consisted of patients with CML in AP or BC and patients with relapsed/refractory Ph+ ALL and Ph+ ALL patients with MRD, with or without previous nilotinib treatment. Patients were treated with 300mg nilotinib BID during the escalation phase (12 months) with increasing doses of ruxolitinib. The dose expansion phase (12 months) began following the determination of the MTD of the combination and the decision to explore the cohort for confirmation of RPIID. In this phase, safety and tolerability of the MTD and/or potential RPIID was to be further evaluated, with the purpose of establishing that this dose is suitable for use in this patient group.
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.

Drug: 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.




Primary Outcome Measures :
  1. Occurrence of dose limiting toxicities (DLTs) [ Time Frame: Baseline, up to day 28 (equals first cycle) ]
    Occurrence of DLTs during cycle 1


Secondary Outcome Measures :
  1. Safety and tolerability profile of nilotinib and ruxolitinib administered in combination [ Time Frame: Baseline, up to month 12 ]
    Maximum Tolerated Dose (MTD) and/or Recommended Phase II Dose (RPIID) of ruxolitinib in combination with nilotinib. (timeframe, baseline up to month 12)

  2. Trough levels of nilotinib and ruxolitinib administered in combination [ Time Frame: Baseline, up to month 12 ]
    Trough levels will be determined by measuring the minimum plasma concentration (Cmin).

  3. Clinical activity of nilotinib and ruxolitinib administered in combination [ Time Frame: Baseline and at 3, 6, and 12 months ]
    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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02253277


Locations
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Germany
Novartis Investigative Site
Berlin, Germany, 13353
Novartis Investigative Site
Frankfurt, Germany, 60590
Novartis Investigative Site
Jena, Germany, 07740
Novartis Investigative Site
Leipzig, Germany, 04103
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Principal Investigator: Andreas Hochhaus, Prof. Dr. med. Universitätsklinikum Jena

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02253277     History of Changes
Other Study ID Numbers: CAMN107YDE19
First Posted: October 1, 2014    Key Record Dates
Last Update Posted: May 1, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
CML, Ph+ ALL

Additional relevant MeSH terms:
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Leukemia
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases