Novartis PhII Ceritinib (LDK378) in R/R ALK+ Hem Malignancies

NCT02343679 | Withdrawn Phase 2

• 1 other identifier: Pro00056623
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase II, single arm, unblinded study of ceritinib in patients with rel/ref hematologic malignancies. Up to 24 evaluable subjects will be enrolled with an interim analysis for efficacy after the first 9 subjects are enrolled. Any subject who takes at least one dose of study drug will be evaluable for safety. Only subjects who complete at least 1 cycle of study drug and have clear progression on physical exam or have had at least one restaging study will be considered evaluable for response. Each subject will receive the same dose of 750mg po daily at the study entry. Subjects with stable disease or better will be allowed to continue study drug until disease progression or until intolerable adverse events or patient or physician decision. Intrapatient dose reductions will be allowed for adverse events. This is a multicenter study with Duke as the lead site. Blood and tissue samples, will be collected and used for exploratory analysis.

Conditions

Hematologic Malignancies

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  ORR defined as CR + PR. Stable disease of at least 3 months will also be reported.

  5 years

Secondary Outcomes (1)

• Progression Free Survival (PFS)

  5 years

Study Arms (1)

Ceritinib for ALK + patients

EXPERIMENTAL

all ALK + hematologic malignancies patients will receive ceritinib

Drug: ceritinib

Interventions

ceritinib DRUG

Ceritinib will be administered to ALK + hematologic malignancies orally at the 750mg/day dose that has been calculated as the maximum tolerated dose in prior phase I trials in lung cancer patients. Intra patient dose reductions will be allowed for toxicities. Subjects with stable disease or better will be allowed to continue study drug until disease progression or until intolerable adverse events or patient or physician choice.

Also known as: LDK378

Ceritinib for ALK + patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Alk+R/R hematologic malignancy including but not limited to ALK+ALCL or ALK+LBCL \> 1 prior standard cytotoxic regimen
• Age \>18
• ECOG performance status \<2
• Evidence of measurable or evaluable disease
• Toxicities ≤ grade 2 due to prior therapies Exception: any grade alopecia
• Platelets \>75 x 109/L
• ANC\>1.5 x 109/L
• AST/ALT\<3.0 x ULN, except liver involvement by their lymphoma, include if AST/ALT\<5 x ULN.
• Total Bilirubin\<1.5 x ULN, (includes gilbert's syndrome if total bilirubin \<3.0 x ULN and direct bilirubin \<1.5 x ULN)
• Potassium, magnesium, total calcium and phosphorous \> lower limits of normal
• Calculated or measured CrCl\> 30ml/min
• Ability to provide written informed consent
• Willing/able to comply with scheduled visits, treatment plans, laboratory tests and other procedures
• Women/men of reproductive potential must agree to use effective birth control during study and for 3 months after receiving study drug.
• Must have existing tissue available for correlative studies

You may not qualify if:

• No chemotherapy, radiation or surgical resection of malignancy \< 3 weeks before start of study drug
• Prior therapy with other ALK inhibitor investigational agents except crizotinib
• Active, uncontrolled, serious infection or medical or psychiatric illness likely to interfere with trial
• Known HIV infection
• Extensive disseminated bilateral interstitial fibrosis or interstitial lung disease, (history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, obliterative bronchiolitis or clinically significant radiation pneumonitis) i.e. affecting daily living or requiring ongoing therapeutic intervention.
• Symptomatic CNS metastases and neurologically unstable or increasing doses of steroids \< 2 weeks prior to study entry
• Major surgery 4 weeks before initiating protocol therapy.
• Hypersensitivity to microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide, magnesium stearate
• Diagnosis or treatment for malignancy other than NHL \< 3 years before Day 1 of protocol therapy. Exceptions:
• Basal or squamous cell carcinoma of the skin
• In situ malignancy - completely resected.
• Prostate cancer treated with prostatectomy or radiotherapy \> 2 years before Day 1 of protocol therapy and PSA is undetectable
• In situ malignancy - completely resected
• Current treatment with another investigational agent \< 14 days before enrollment. Other non-treatment studies allowed if it won't interfere with study participation.
• Myocardial infarction or unstable angina 6 months before enrollment or New York Hospital Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.

Sponsors & Collaborators

• Anne Beaven, MD: lead
• Novartis: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

ceritinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Anne Beaven, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: December 3, 2014
• First Posted: January 22, 2015
• Study Start: May 1, 2015
• Primary Completion: October 1, 2020
• Study Completion: October 1, 2022
• Last Updated: February 1, 2017

Record last verified: 2017-01

Locations

US (1)