Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as navitoclax, A-855071.0, BcI-2 Family Protein Inhibitor ABT-263
ABT-263 · 20 trials · 25 indications
Reduction in spleen volume is measured by magnetic resonance imaging (MRI) or computed tomography (CT), per International Working Group (IWG) criteria.
Reduction in spleen volume is measured by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT), per International Working Group (IWG) criteria.
Reduction in spleen volume is measured by magnetic resonance imaging/computerized tomography (MRI/CT).
The investigators will monitor each subject for clinical and lab evidence of adverse events on a routine basis through out the study. The investigators will question each subject regarding any adverse effects that they have experienced and record any events on the care report forms. All adverse events will be followed to a satisfactory clinical resolution.
Physical exam, blood pressure, pulse, body temperature will be measured and recorded
Chemistry, hematology, urinalysis lab tests will be measured and recorded. All clinically significant values will be followed by the investigator to a satisfactory clinical resolution.
The Bayesian optimal interval (BOIN) design will be employed to find the MTD. The BOIN design is implemented in a simple way. It is more flexible and possesses superior operating characteristics that are comparable to those of the more complex model based designs.
A 90% confidence interval will be computed for the CR rate by cycle 4.
The RP2D is the minimally safe and biologically effective dose. The minimally safe dose is the highest dose level at which \<2 of 6 participants experience a dose limiting toxicity (DLT). See subsequent primary outcome for the DLT definition. With respect to safety, the RP2D will also consider laboratory evidence of platelet recovery. Evaluation of efficacy will be done in real time prioritizing full complete response (see subsequent secondary outcome for the objective response criteria) when possible for AML/MDS/MDS-MPN and transfusion independence/blast reduction/TSS improvement/splenic reduction for myelofibrosis.
DLT is defined by hematologic or non-hematologic adverse event (AE) per protocol (section 5.4); A treatment-related death is a DLT; AEs are graded based on NCI CTCAE v5.0 and must be considered unrelated to the underlying disease or co-morbidity to be a DLT.
Dose limiting toxicities for dose escalation purposes will be determined on events that occur during the first 28-day cycle of navitoclax.
Maximum Observed Plasma Concentration (Cmax) of Navitoclax.
Maximum Observed Plasma Concentration (Cmax) of Celecoxib.
Tmax defined as time to maximum observed plasma concentration of Navitoclax.
Tmax defined as time to maximum observed plasma concentration of Celecoxib.
Area under the plasma concentration-time curve from time zero to the last measurable concentration of Navitoclax.
Area under the plasma concentration-time curve from time zero to the last measurable concentration of Celecoxib.
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
Change in QTcF (Part 3).
Maximum observed plasma concentration (Cmax) of venetoclax + navitoclax
Area under the plasma concentration-time curve (AUC) of venetoclax + navitoclax
Time to Cmax (Tmax) of Venetoclax + Navitoclax
Apparent oral clearance (CL/F) of venetoclax + navitoclax
A DLT is any Grade 3 or higher non-hematologic adverse event (AE) with exceptions outlined in the protocol. AEs and toxicities that occur beyond the DLT assessment period will also be evaluated by the investigator and AbbVie and may be considered as dose-limiting.
Assess the oral bioavailability of Formulation B1, Formulation B2, Formulation C, and Formulation D relative to that of Formulation A being assessed in ongoing Phase 1/2a ABT-263 studies
• assess the safety profile of ABT-263 in combination with erlotinib; • study the pharmacokinetic interaction between ABT-263 and erlotinib; • determine the maximum tolerated dose (MTD) of ABT-263 when administered with erlotinib
• assess the safety profile of ABT-263 in combination with irinotecan; • study the pharmacokinetic interaction between ABT-263 and irinotecan; • determine the maximum tolerated dose (MTD) of ABT-263 when administered with irinotecan.s
• assess the safety profile of ABT-263 as a monotherapy
Evaluate safety at the defined recommended Phase 2 dose (RPTD) and schedule of ABT-263 in combination with Paclitaxel
Evaluate preliminary data regarding objective response rate (ORR), progression free survival (PFS), time to tumor progression (TTP), overall survival (OS), duration of overall response, and, ECOG performance status
An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An SAE is one that: results in death, hospitalization, prolongation of hospitalization, or persistent or significant disability/incapacity; is life-threatening, a congenital anomaly, or other important medical event. Events were graded as 1=mild, 2=moderate, 3=severe, 4=life-threatening, or 5=death. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related. A treatment-emergent adverse event is defined as any adverse event with onset or worsening reported by a subject from the time that the first dose of study drug is administered until 30 days have elapsed following discontinuation of study drug administration. Deaths category included non treatment emergent deaths.
DLTs were graded according to NCI CTCAE version 3.0 (grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=life threatening; grade 5=death). Any of the following events, considered possibly or probably related to the administration of navitoclax, were considered a DLT: Grade 4 thrombocytopenia (\< 25,000/mm\^3); platelet counts \< 25,000/mm\^3, Grade 2 or higher bleeding associated with thrombocytopenia; all other Grade 3, 4 or 5 adverse events were considered a DLT. Exceptions included: Grade 3, 4 febrile neutropenia less than 7 days; Grade 3, 4 leukopenia; Grade 3, 4 lymphopenia; Grade 3 nausea, vomiting and/or diarrhea unless unresponsive to treatment; Grade 2 toxicity that requires dose modification or delay of \> 1 week.
The MTD was defined as the dose at which 30% of participants experienced a DLT during the first cycle. DLTs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0 (grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=life threatening; grade 5=death). Any of the following events, considered possibly or probably related to the administration of navitoclax, were considered a DLT: Grade 4 thrombocytopenia (\< 25,000/mm\^3); platelet counts \< 25,000/mm\^3, Grade 2 or higher bleeding associated with thrombocytopenia; all other Grade 3, 4 or 5 adverse events were considered a DLT. Exceptions included: Grade 3, 4 febrile neutropenia less than 7 days; Grade 3, 4 leukopenia; Grade 3, 4 lymphopenia; Grade 3 nausea, vomiting and/or diarrhea unless unresponsive to treatment; Grade 2 toxicity that requires dose modification or delay of \> 1 week.
The RPTD was determined based on observed DLTs and/or determination of the MTD in phase 1. (See Outcome Measures 2 and 3 above for definition of DLT and MTD.)
The AUC24 was derived and reported from Cycle 1 Day 1 values and Cycle 1 Day 14 values; the pre-dose value taken on Day 14 was utilized as 24-hour timepoint on Day 14 to generate AUC24 for Day 14.
The AUC24 was derived and reported from Cycle 1 Day 1 values and Cycle 1 Day 14 values; the pre-dose value taken on Day 14 was utilized as 24-hour timepoint on Day 14 to generate AUC24 for Day 14.
For t1/2, the harmonic mean and psuedo-standard deviation are used.
An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An SAE is one that: results in death, hospitalization, prolongation of hospitalization, or persistent or significant disability/incapacity; is life-threatening, a congenital anomaly, or other important medical event. Events were graded as 1=mild, 2=moderate, 3=severe, 4=life-threatening, or 5=death. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related. A treatment-emergent adverse event is defined as any adverse event with onset or worsening reported by a subject from the time that the first dose of study drug is administered until 30 days have elapsed following discontinuation of study drug administration. Deaths category included non treatment emergent deaths.
1a: Determination of dose limiting toxicity (DLT) and maximum tolerated dose (MTD) under a 14/21 day dosing schedule
Phase 1b: Determination of ABT-263 dose limiting toxicity (DLT) and maximum tolerated dose (MTD) under a 21 day continuous dosing schedule.
Phase 2a: Continued assessment of the safety profile of ABT-263 at the Recommended Phase 2 Dose (RPTD) and schedule under a 21 day continuous dosing.
Phase 2a: Assessment of the preliminary efficacy signals of ABT-263, including biomarker assessment, at the Recommended Phase 2 Dose (RPTD) and schedule under a 21 day continuous dosing.
Continued assessment of the safety profile of ABT-263.
Continued assessment of the preliminary efficacy signals of ABT-263.
| Arm | Type | Description |
|---|---|---|
| Placebo for Navitoclax + Ruxolitinib | ACTIVE_COMPARATOR | Placebo for navitoclax tablets were administered orally once daily (QD) per Baseline platelet count (\>150 × 10\^9/L starting dose of 200 mg; ≤150 × 10\^9/L starting dose of 100 mg, which could be increased to 200 mg QD after 7 days provided platelet count is ≥75 × 10\^9/L). Placebo for navitoclax didn't exceed 200 mg QD for first 24 weeks of treatment. After Week 25, Day 1 visit, placebo for navitoclax dose may be increased to 300 mg QD at Investigator's discretion for those with suboptimal spleen response defined as failure to achieve spleen volume reduction of at least 10% per imaging. Ruxolitinib tablets were administered orally twice daily (BID) per Baseline platelet count (\>200 × 10\^9/L starting dose of 20 mg; 100-200 × 10\^9/L starting dose of 15 mg). Participants will continue their treatment until end of clinical benefit, unacceptable toxicity, or they meet other protocol criteria for discontinuation (whichever occurs first). |
| Navitoclax + Ruxolitinib | EXPERIMENTAL | Navitoclax tablets were administered orally once daily (QD) per Baseline platelet count (\>150 × 10\^9/L starting dose of 200 mg; ≤150 × 10\^9/L starting dose of 100 mg, which could be increased to 200 mg QD after 7 days provided platelet count is ≥75 × 10\^9/L). Navitoclax didn't exceed 200 mg QD for first 24 weeks of treatment. After Week 25, Day 1 visit, navitoclax dose may be increased to 300 mg QD at Investigator's discretion for those with suboptimal spleen response defined as failure to achieve spleen volume reduction of at least 10% per imaging. Ruxolitinib tablets were administered orally twice daily (BID) per Baseline platelet count (\>200 × 10\^9/L starting dose of 20 mg; 100-200 × 10\^9/L starting dose of 15 mg). Participants will continue their treatment until end of clinical benefit, unacceptable toxicity, or they meet other protocol criteria for discontinuation (whichever occurs first). |
| Arm A: Navitoclax + Ruxolitinib | EXPERIMENTAL | Participants will receive navitoclax tablets once daily and ruxolitinib tablets twice daily. |
| Arm B: Best Available Therapy (BAT) | ACTIVE_COMPARATOR | Participants will receive one of the BAT options, per the investigator's discretion. |
| Arm C: Continued Access for Navitoclax | EXPERIMENTAL | Participants will receive navitoclax tablets once daily. |
| Navitoclax + ruxolitinib (Cohort 1a) | EXPERIMENTAL | Participants must have received ruxolitinib for at least 12 weeks and on stable dose of ≥10 mg tablets orally twice daily (BID) for ≥8 weeks prior to the 1st dose of navitoclax. Navitoclax tablets are administered once daily (QD) at a starting dose of 50 mg. This was increased after approximately ≥7 days to next dose level if platelet count is ≥75 × 10\^9/L up to a maximum dose of navitoclax 300 mg QD. Participants continued their treatment until the end of clinical benefit, unacceptable toxicity, or they met other protocol criteria for discontinuation (whichever occurred first). |
| Navitoclax + ruxolitinib (Cohort 1b) | EXPERIMENTAL | Those receiving ruxolitinib at Screening must be on a stable dose ≥10 mg tablets orally twice daily (BID) for ≥ 4 weeks prior to 1st dose of navitoclax. Those not receiving ruxolitinib at Screening received 10 mg ruxolitinib BID starting on Day 1. Navitoclax tablets were administered orally once daily (QD) per Baseline platelet count (\>150 × 10\^9/L starting dose of 200 mg; ≤150 × 10\^9/L starting dose of 100 mg, which could be increased to 200 mg QD after 7 days provided platelet count is ≥75 × 10\^9/L). Navitoclax didn't exceed 200 mg QD for first 24 weeks of treatment. After Week 24 disease assessment, navitoclax dose was increased to 300 mg QD at discretion of the Investigator for those with suboptimal spleen response defined as failure to achieve spleen volume reduction of at least 10% per imaging. Participants continued their treatment until the end of clinical benefit, unacceptable toxicity, or they met other protocol criteria for discontinuation (whichever occurred first). |
| Navitoclax (Cohort 2) | EXPERIMENTAL | Participants must have received prior treatment with a Janus Kinase 2 (JAK-2) inhibitor. Those with Baseline platelet count \>150 × 10\^9/L initiated navitoclax film-coated tablets orally once daily (QD) at the starting dose of 200 mg. Those with a Baseline platelet count ≤150 × 10\^9/L initiated navitoclax film-coated tablets orally once daily (QD) at the starting dose of 100 mg, which could be increased to 200 mg once daily after 7 days provided the platelet count is ≥75 × 10\^9/L. Navitoclax didn't exceed 200 mg QD for the first 24 weeks of treatment. After Week 24 disease assessment, navitoclax dose may be increased to 300 mg QD at discretion of the Investigator for those with suboptimal spleen response defined as failure to achieve spleen volume reduction of at least 10% per imaging. Participants continued their treatment until the end of clinical benefit, unacceptable toxicity, or they met other protocol criteria for discontinuation (whichever occurred first). |
| Navitoclax + ruxolitinib (Cohort 3) | EXPERIMENTAL | Prior treatment with a Janus Kinase 2 (JAK-2) or Bromodomain and Extra-Terminal motif (BET) proteins inhibitor was prohibited. Ruxolitinib tablets administered orally twice daily (BID) based on Baseline platelet count as per the local approved label. Navitoclax tablets were administered orally once daily (QD) per Baseline platelet count (\>150 × 10\^9/L starting dose of 200 mg; ≤150 × 10\^9/L starting dose of 100 mg, which could be increased to 200 mg QD after 7 days provided platelet count is ≥75 × 10\^9/L). Navitoclax didn't exceed 200 mg QD for first 24 weeks of treatment. After Week 24 disease assessment, navitoclax dose may be increased to 300 mg QD at discretion of Investigator for those with suboptimal spleen response defined as failure to achieve spleen volume reduction of at least 10% per imaging. Participants continued their treatment until the end of clinical benefit, unacceptable toxicity, or they met other protocol criteria for discontinuation (whichever occurred first). |
| Navitoclax, ABT-263 | EXPERIMENTAL | - |
| A | ACTIVE_COMPARATOR | - |
| B | EXPERIMENTAL | - |
| C | EXPERIMENTAL | - |
| Treatment (navitoclax, decitabine, venetoclax) | EXPERIMENTAL | This is a single-center trial of navitoclax, venetoclax and decitabine in adult patients with R/R HR-MDS who have previously failed HMA therapy. This trial was intended to be a Phase 1/2 trial but the trial never moved forward to Phase 2. In the phase I dose escalation portion, patients will receive navitoclax in combination with standard dosing of venetoclax and decitabine. The maximally tolerated dose (MTD) will be the recommended phase II dose (RP2D). Previously, navitoclax in combination with venetoclax and chemotherapy in ALL found the MTD to 50mg of nativoclax po. In the phase II dose expansion portion, patients will receive navitoclax at the RP2D in combination with standard dose venetoclax and decitabine. Patients will continue on treatment with navitoclax, venetoclax and decitabine until relapse, dose-limiting toxicity, availability of alternate therapy or withdrawal of consent. |
| Dose Level 0: Decitabine + Venetoclax + Navitoclax [AML and Non-AML] | EXPERIMENTAL | Dose Level 0 \[AML and Non-AML\] Decitabine \[intravenously (IV) preferred\] Venetoclax Cycle 1: ramp-up days 1-2 and days 3-14 absence of strong/moderate CYP3A inhibitor and reduced doses dependent on presence of moderate or strong CYP3A inhibitor Cycle 2+: dosing days 1-14 Navitoclax Cycle 1: dosing days 3-14; Cycle 2+: dosing on days 1-14 Cycle length=28 days Participants are treated indefinitely until disease progression, unacceptable toxicity or withdrawal for other reasons. |
| Dose Level 1: Venetoclax + Decitabine + Navitoclax [AML and Non-AML] | EXPERIMENTAL | Dose Level 1 \[AML and Non-AML\] Decitabine \[intravenously (IV) preferred\] Cycle 1+: dosing on days 1-5 Venetoclax \[orally\] Cycle 1: ramp-up starting on day 1-2 then days 3-14 continued dosing in absence of strong/moderate CYP3A inhibitor and reduced doses dependent on presence of moderate or strong CYP3A inhibitor Cycle 2+: dosing days 1-14 Navitoclax \[orally\] Cycle 1: Dosing days 3-14 Cycle 2+: dosing on days 1-14 Cycle length=28 days Participants are treated indefinitely until disease progression, unacceptable toxicity or withdrawal for other reasons. |
| Dose Level 2: Venetoclax + Decitabine + Navitoclax [AML] | EXPERIMENTAL | Dose Level 2 \[AML\] Decitabine \[intravenously (IV) preferred\] Cycle 1+: dosing on days 1-5 Venetoclax \[orally\] Cycle 1: ramp-up on day 1-2, days 3-21 continued dosing in absence of strong/moderate CYP3A inhibitor and reduced doses dependent on presence of moderate or strong CYP3A inhibitor Cycle 2+: dosing on days 1-21 Navitoclax \[orally\] Cycle 1: dosing on days 3-14 Cycle 2+: dosing on days 1-14 Cycle length=28 days Participants are treated indefinitely until disease progression, unacceptable toxicity or withdrawal for other reasons. |
| Dose Level -1: Venetoclax + Decitabine + Navitoclax [Non-AML] | EXPERIMENTAL | Dose Level -1 \[Non-AML\] Decitabine \[intravenously (IV) preferred\] Cycle 1+:dosing \[intravenously (IV) preferred\] on days 1-3 Venetoclax \[orally\] Cycle 1: ramp-up of starting day 1-2 then days 3-7 continued dosing in absence of strong/moderate CYP3A inhibitor and reduced doses dependent on presence of moderate or strong CYP3A inhibitor Cycle 2+: dosing on days 1-7 Navitoclax \[orally\] Cycle 1: Dosing days 3-14 Cycle 2+: continued dosing on days 1-14 Cycle length=28 days Participants are treated indefinitely until disease progression, unacceptable toxicity or withdrawal for other reasons. |
| Recommended Phase 2 Dose Level: Venetoclax + Decitabine + Navitoclax [AML and Non-AML] | EXPERIMENTAL | RP2D \[AML and Non-AML\] Decitabine \[intravenously (IV) preferred\] To be determined based on dose escalation design. Venetoclax \[orally\] To be determined based on dose escalation design. Navitoclax \[orally\] To be determined based on dose escalation design. Cycle length=28 days Participants are treated indefinitely until disease progression, unacceptable toxicity or withdrawal for other reasons. |
| Part 1: Navitoclax Monotherapy | EXPERIMENTAL | Participants will receive various doses of navitoclax once daily (QD). |
| Part 2: Navitoclax + Ruxolitinib Combination Therapy | EXPERIMENTAL | Participants will receive various doses of navitoclax once daily (QD) in combination with ruxolitinib twice daily (BID). |
| Part 3: Navitoclax Monotherapy | EXPERIMENTAL | Participants will receive navitoclax once daily (QD). |
| Part 4: Navitoclax + Celecoxib | EXPERIMENTAL | Participants will receive navitoclax once daily (QD) starting on Day 3. Participants will also receive celecoxib single dose on Day 1 and Day 7. |
| Part 5: Navitoclax + Ruxolitinib Combination Therapy | EXPERIMENTAL | Participants will receive ruxolitinib BID and navitoclax QD for drug-drug interaction (DDI) assessment, followed by continued administration of navitoclax in combination with ruxolitinib. |
| Venetoclax + Navitoclax + Chemotherapy | EXPERIMENTAL | Venetoclax weight-adjusted doses administered orally every day (QD) starting on Day 1 + navitoclax various, weight-adjusted doses administered orally QD starting on Day 3 + chemotherapy (peg-asparaginase \[or any other forms of asparaginase\], vincristine, dexamethasone) and tyrosine kinase inhibitor \[TKI, if applicable\]). This regimen and any of its components may be delayed, reduced or omitted at the discretion of the Investigator. |
| Arm A (navitoclax and rifampin) | EXPERIMENTAL | - |
| ABT-263 + etoposide/cisplatin | EXPERIMENTAL | - |
| Sequence I | EXPERIMENTAL | - |
| Sequence II | EXPERIMENTAL | - |
| Sequence III | EXPERIMENTAL | - |
| Sequence IV | EXPERIMENTAL | - |
| Sequence V | EXPERIMENTAL | - |
| Sequence VI | EXPERIMENTAL | - |
| Sequence VII | EXPERIMENTAL | - |
| Sequence VIII | EXPERIMENTAL | - |
| Sequence IX | EXPERIMENTAL | - |
| Sequence X | EXPERIMENTAL | - |
| Sequence XI | EXPERIMENTAL | - |
| Sequence XII | EXPERIMENTAL | - |
| Sequence XIII | EXPERIMENTAL | - |
| Sequence XIV | EXPERIMENTAL | - |
| Sequence XVI | EXPERIMENTAL | - |
| Sequence XV | EXPERIMENTAL | - |
| Arm A (ABT-263 and erlotinib) | EXPERIMENTAL | - |
| Arm B (ABT-263 and irinotecan) | EXPERIMENTAL | - |
| Arm C (ABT-263 monotherapy) | EXPERIMENTAL | - |
| gemcitabine +ABT-263 | EXPERIMENTAL | - |
| ABT-263 + rituximab | EXPERIMENTAL | - |
| Paclitaxel and ABT-263 | EXPERIMENTAL | - |
| Navitoclax 14/21 Day Cycle: 10 mg | EXPERIMENTAL | Navitoclax 10 mg administered for 14 consecutive days followed by 7 days off drug to complete a 21-day cycle. |
| Navitoclax 14/21 Day Cycle: 110 mg | EXPERIMENTAL | Navitoclax 110 mg administered for 14 consecutive days followed by 7 days off drug to complete a 21-day cycle. |
| Navitoclax 14/21 Day Cycle: 200 mg | EXPERIMENTAL | Navitoclax 200 mg administered for 14 consecutive days followed by 7 days off drug to complete a 21-day cycle. |
| Navitoclax 14/21 Day Cycle: 250 mg | EXPERIMENTAL | Navitoclax 250 mg administered for 14 consecutive days followed by 7 days off drug to complete a 21-day cycle. |
| Navitoclax 21/21 Day Cycle: 125 mg | EXPERIMENTAL | Navitoclax 125 mg administered for 21 consecutive days to complete a 21-day cycle. |
| Navitoclax 21/21 Day Cycle: 200 mg | EXPERIMENTAL | Navitoclax 200 mg administered for 21 consecutive days to complete a 21-day cycle. |
| Navitoclax 21/21 Day Cycle: 250 mg | EXPERIMENTAL | Navitoclax 250 mg administered for 21 consecutive days to complete a 21-day cycle. |
| Navitoclax 21/21 Day Cycle: 300 mg | EXPERIMENTAL | Navitoclax 300 mg administered for 21 consecutive days to complete a 21-day cycle. |
| Phase 2: Navitoclax 100 mg | EXPERIMENTAL | Navitoclax 100 mg in participants with CLL who had relapsed following any (but no more than 5) prior myelosuppressive/chemotherapy treatment regimen(s). |
| Phase 2: Navitoclax 250 mg | EXPERIMENTAL | Navitoclax 250 mg in participants with CLL who had relapsed following any (but no more than 5) prior myelosuppressive/chemotherapy treatment regimen(s). |
| Phase 1 and Phase 2a | EXPERIMENTAL | - |
| Phase 1a and 1b | EXPERIMENTAL | Relapsed or refractory lymphoid malignancies |
| Arm A (Phase 2a) | EXPERIMENTAL | Relapsed or refractory follicular lymphoma |
| Arm B (Phase 2a) | EXPERIMENTAL | Relapsed or refractory mantle cell, peripheral T-cell, cutaneous T-cell lymphoma including mycosis fungoides and Sezary syndrome, or other indolent B-cell lymphomas such as marginal zone lymphoma |
| Extension Study | EXPERIMENTAL | Relapsed or refractory follicular lymphoma or Relapsed or refractory mantle cell, peripheral T-cell, cutaneous T-cell lymphoma including mycosis fungoides and Sezary syndrome, or other indolent B-cell lymphomas such as marginal zone lymphoma |
| Name | Type | Description |
|---|---|---|
| Placebo for Navitoclax | DRUG | Film-coated tablet; Oral |
| Ruxolitinib | DRUG | Tablet; Oral |
| Navitoclax | DRUG | Film-coated tablet; Oral |
| Best Available Therapy (BAT) | DRUG | Tablet/Capsule; Oral or Solution for Subcutaneous Injection |
| ABT-263 | DRUG | Oral repeating dose |
| rituximab | DRUG | Intravenous repeating dose |
| Venetoclax | DRUG | Given PO |
| Decitabine | DRUG | Given IV |
| Bone Marrow Biopsy | PROCEDURE | Undergo bone marrow biopsy |
| Biospecimen Collection | PROCEDURE | Undergo collection of blood |
| Laboratory Biomarker Analysis | OTHER | Correlative studies |
| Quality-of-Life Assessment | OTHER | Ancillary studies |
| Celecoxib | DRUG | Capsule; Oral |
| Chemotherapy | DRUG | peg-asparaginase (or other form of asparaginase, per local standard of care (intravenous) + vincristine (intravenous) + dexamethasone (oral) + tyrosine kinase inhibitor (TKI) (if applicable, oral) |
| Rifampin | DRUG | Subjects will be dosed with Navitoclax, then, dosed with Navitoclax in combination with Rifampin. |
| FCR | DRUG | Rituximab will be given by intravenous infusion for 1 day out of each 28 day cycle; Fludarabine will be given by intravenous infusion for 3 days out of each 28 day cycle; and Cyclophosphamide will be given by intravenous infusion for 3 days out of each 28 day cycle |
| BR | DRUG | Rituximab will be given by intravenous infusion for 2 days out of each 28 day cycle and Bendamustine will be given by intravenous infusion for 2 days out of each 28 day cycle |
| etoposide/cisplatin | DRUG | etoposide = 100 mg/m2 Days 1-3 of each Cycle; Max duration 6 cycles. cisplatin = 75 mg/m2 Day 1 of each Cycle; Max duration 6 cycles |
| erlotinib | DRUG | 150 mg of erlotinib is taken orally once daily. |
| irinotecan (3-week schedule) | DRUG | 180 mg/m2 over 90 minutes, irinotecan will be given by intravenous infusion on Day 1 of each 21 day cycle. Note - The dose and schedule is subject to change based on the toxicities observed. |
| irinotecan (weekly schedule) | DRUG | 75 mg/m2 over 45 minutes, irinotecan will be given by intravenous infusion on Days 1 and 8 of each 21 day cycle. Note - The dose and schedule is subject to change based on the toxicities observed. |
| gemcitabine | DRUG | Gemcitabine 1000 mg/m2 will be given by intravenous infusion on Day 1 and Day 8 of each 21 day cycle. Gemcitabine 1000 mg/m2 will be given by intravenous infusion on days 1, 8 and 15 of each 28 day cycle. |
| paclitaxel | DRUG | 175 mg/m2 over 3 hours of paclitaxel will be given by intravenous infusion on Day 1 of each 21 day cycle. Note - The dose and schedule is subject to change based on the toxicities observed. |
Inclusion Criteria: * Documented diagnosis of Primary MyeloFibrosis (MF) as defined by World Health Organization (WHO) classification or Secondary MF (post polycythemia vera \[PPV\] - MF or Post Essential Thrombocythemia \[PET\] - MF) . * Must be able to complete the MF Symptom Assessment Form (MFS...
ABT-263 is an investigational small molecule being developed by AbbVie Inc. for oncology indications. It has been studied in chronic lymphocytic leukemia and other CD20-positive lymphoid malignancies, as well as in solid tumors including small cell lung cancer. ABT-263 remains in clinical development and is not approved for any indication.
ABT-263 has been studied in chronic lymphocytic leukemia, including a Phase 2 trial in previously untreated patients with B-cell CLL. It has also been evaluated in other lymphoid malignancies and in solid tumors. ABT-263 is investigational and has not been approved for the treatment of CLL or any other condition.
ABT-263 is being developed by AbbVie Inc., which trades on the New York Stock Exchange under the ticker ABBV. AbbVie sponsored the clinical trials of ABT-263 in chronic lymphocytic leukemia, lymphoid malignancies, and solid tumors.
ABT-263 is in Phase 1 development overall, though one completed trial was a Phase 2 study in chronic lymphocytic leukemia. All four listed trials of ABT-263 have been completed, and no trials are currently active. ABT-263 is investigational and has not been approved by the FDA.
ABT-263 has been evaluated in four completed trials: NCT01087151, a Phase 2 study in previously untreated B-cell chronic lymphocytic leukemia; NCT01009073, a Phase 1 study in solid tumors; NCT00982566, a Phase 1 oral bioavailability study; and NCT00891605, a Phase 1 study with paclitaxel in solid tumors.