A Phase 2 Study of ABT-199 in Combination With Ibrutinib in the Treatment of Patients With Relapsed or Refractory Mantle Cell Lymphoma (AIM Study)
Overview
- Phase
- Phase 2
- Intervention
- ABT-199
- Conditions
- Mantle Cell Lymphoma
- Sponsor
- Peter MacCallum Cancer Centre, Australia
- Enrollment
- 37
- Locations
- 2
- Primary Endpoint
- Complete response measured using IWG at 16 weeks
- Status
- Active, not recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This research will test the combination of two new drugs, called ibrutinib and ABT199, taken together in the treatment of Mantle Cell Lymphoma. Other studies have indicated the potential for these drugs to be used in the treatment of participants with Mantle Cell Lymphoma. In this study, the investigators will test the combination of the two drugs together, in order to determine what effects (good and bad) it has on mantle cell lymphoma.
This study has two phases. The first phase is the Primary Evaluation Phase and will closely monitor the effects of ibrutinib and ABT199 for a period of 13 months. Participants who complete 13 months of treatment and continue benefiting from the study treatments will be allowed to continue both drugs until progression or intolerance in the Continuation Phase. The purpose of this phase is to provide patients with continuing access to both ibrutinib and ABT199. Patients will receive routine care from clinician, who will record any sideeffects that may be experienced.
This is one of the first trials in the world to study the combination of ibrutinib and ABT199 together. Therefore the effectiveness of the combination of the study drugs will be assessed, as will how they affect mantle cell lymphoma and how it develops resistance to the treatments. The investigators also do not know whether combining the two drugs together will cause unexpected side effects. Therefore, the study will monitor patients closely and perform scans, blood tests, bone marrow biopsies and other tests at regular intervals.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subject must be \>/= 18 years of age.
- •Subject must have a confirmed diagnosis of Mantle Cell Lymphoma (MCL) according to WHO (2008) criteria, and have received at least one prior line of systemic therapy for MCL.
- •Subject requires treatment in the opinion of the investigator, and has at least one site of radiographically assessable disease not previously irradiated (lymph node with largest diameter \>/= 1.5cm, or unequivocal hepatomegaly / splenomegaly)
- •Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of \</=
- •Subject must have adequate bone marrow function at Screening as follows:
- •Absolute Neutrophil Count (ANC) \>/= 1.0 x 109/L (neutropenia due to marrow infiltration may be supported by growth factors);
- •Platelets \>/= 50 x 109/L (entry platelet count must be independent of transfusion within 7 days).
- •Subject must have adequate coagulation, renal, and hepatic function, per laboratory reference range at Screening as follows:
- •aPTT and PT not to exceed 1.5 × the upper limit of normal (ULN);
- •Serum creatinine not to exceed 2 x ULN, and a calculated creatinine clearance of at least 50 mL/min using the Cockcroft-Gault equation or a 24-hour urine collection;
Exclusion Criteria
- •Subject has undergone an allogeneic stem cell transplant within the last 6 months or currently has active graft-vs-host disease requiring the use of immunosuppressants.
- •Subject has active and uncontrolled autoimmune cytopenias (for 2 weeks), including autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP).
- •Subject has known central nervous system involvement by MCL.
- •Subject previously participated in an ibrutinib clinical trial or subject previously received a Bruton's tyrosine kinase (BTK) inhibitor other than ibrutinib
- •Subject has received the following within 30 days prior to the first dose of study drug:
- •Monoclonal antibody given with anti-neoplastic intent.
- •Subject has received any of the following within 14 days prior to the first dose of study drug, or has not recovered to less than CTC grade 2 clinically significant adverse effect(s)/toxicity(s) of the previous therapy:
- •Any anti-cancer therapy including chemotherapy, or radiotherapy;
- •Investigational therapy, including targeted small molecule agents.
- •Subject has received the following within 7 days prior to the first dose of study drug:
Arms & Interventions
Ibrutinib + ABT-199
Intervention: ABT-199
Ibrutinib + ABT-199
Intervention: Ibrutinib
Outcomes
Primary Outcomes
Complete response measured using IWG at 16 weeks
Time Frame: Measured at 16 weeks after commencement of treatment.
Secondary Outcomes
- Toxicities measured using CTCAE version 4(Continuously measured while on treatment up to a maximum of 56 weeks)
- Complete response using IWG criteria at 4, 16, 28, 40 and 56 weeks(Assessed at 4, 16, 28, 40 and 56 weeks)
- Duration of response(From first disease response date to the date of earliest recurrance or PD, assessed up to the date when the last patient has their 13 months assessment.)
- Completing 4, 16, 28, 40 and 56 weeks of treatment(Assessed at 4, 16, 28, 40 and 56 weeks)
- Overall response (CR + PR) using IWG criteria at 4, 16, 28, 40 and 56 weeks(Assessed at 4, 16, 28, 40 and 56 weeks)
- Minimal residual disease (MRD) at 4, 16, 28, 40 and 56 weeks(Assessed at 4, 16, 28, 40 and 56 weeks)
- Progression free survival(From start of treatment until the date of first documented progression or date of death from any cause, whichever occures first, assessed up to the date when the last patient has their 13 months assessment.)
- Overall survival(From start of treatment until the date of death from any cause assessed up to the date when the last patient has their 13 months assessment.)
- Time to progression(From start of treatment until the date of first documented progression assessed up to the date when the last patient has their 13 months assessment.)