Chronic Myeloid Leukemia
Conditions
Keywords
CML, Ph+ ALL
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.
Interventions
DRUGNilotinib
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.
DRUGRuxolitinib
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.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of dose limiting toxicities (DLTs) | Baseline, up to day 28 (equals first cycle) | Occurrence of DLTs during cycle 1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability profile of nilotinib and ruxolitinib administered in combination | 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) |
| Trough levels of nilotinib and ruxolitinib administered in combination | Baseline, up to month 12 | Trough levels will be determined by measuring the minimum plasma concentration (Cmin). |
| Clinical activity of nilotinib and ruxolitinib administered in combination | 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 |
Countries
Germany
Outcome results
None listed