A Phase 1 interventional study of Nilotinib and Ruxolitinib in Chronic Myeloid Leukemia, sponsored by Novartis Pharmaceuticals. Completed at 4 sites in Germany. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-05-01.
Sponsored by Novartis Pharmaceuticals (part of Novartis) · Phase 1, Interventional, and Treatment
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.
982 studies on the registry are indexed under Leukemia, Myelogenous, Chronic, BCR-ABL Positive; 109 are open to participants now.
This study's enrollment of 5 is below the median of 43 across 755 interventional studies indexed under Leukemia, Myelogenous, Chronic, BCR-ABL Positive.
Browse Leukemia, Myelogenous, Chronic, BCR-ABL Positive studies →Novartis Pharmaceuticals is the lead sponsor of 2,711 studies on the registry; 218 are open to participants now.
Of its 582 completed or terminated interventional studies of FDA-regulated products, 435 (75%) have results posted.
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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:
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:
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
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 · Drug: Ruxolitinib
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 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.
Occurrence of dose limiting toxicities (DLTs)
Occurrence of DLTs during cycle 1
Time frame: Baseline, up to day 28 (equals first cycle)
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)
Time frame: Baseline, up to month 12
Trough levels of nilotinib and ruxolitinib administered in combination
Trough levels will be determined by measuring the minimum plasma concentration (Cmin).
Time frame: Baseline, up to month 12
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
Time frame: Baseline and at 3, 6, and 12 months
Plan to share: No
No publications or documents are linked to this record.
Ran from Feb 2015 to primary completion in Mar 2018, 36 months.
Of 57 phase 1 interventional studies under Leukemia, Myelogenous, Chronic, BCR-ABL Positive, half reached primary completion within 61 months of starting (the median), counting those still running; a quarter within 41 and three quarters within 104. This study's 36 months is below that.
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This study is completed, as verified in Apr 2019. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Nilotinib · Ruxolitinib
Leukemia, Myelogenous, Chronic, BCR-ABL Positive →