SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT01886872

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

A Randomized Phase III Study of Bendamustine Plus Rituximab Versus Ibrutinib Plus Rituximab Versus Ibrutinib Alone in Untreated Older Patients (>/= 65 Years of Age) With Chronic Lymphocytic Leukemia (CLL)

This randomized phase III trial studies rituximab with bendamustine hydrochloride or ibrutinib to see how well they work compared to ibrutinib alone in treating older patients with previously untreated chronic lymphocytic leukemia. Monoclonal antibodies, such as rituximab, may block cancer growth in different ways by targeting certain cells. Drugs used in chemotherapy, such as bendamustine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether rituximab with bendamustine hydrochloride may work better than rituximab and ibrutinib or ibrutinib alone in treating chronic lymphocytic leukemia.

NCT01886872 CD19 Positive CD20 Positive CD5 Positive Stage I Chronic Lymphocytic Leukemia Stage II Chronic Lymphocytic Leukemia Stage III Chronic Lymphocytic Leukemia Stage IV Chronic Lymphocytic Leukemia
MeSH: Leukemia Leukemia, Lymphoid Leukemia, Lymphocytic, Chronic, B-Cell
HPO: Chronic lymphatic leukemia Leukemia Lymphoid leukemia

5 Interventions

Name: Bendamustine Hydrochloride

Description: Given IV

Type: Drug

Arm I (rituximab, bendamustine hydrochloride)

Name: Ibrutinib

Description: Given PO

Type: Drug

Arm II (ibrutinib) Arm III (ibrutinib, rituximab)

Name: Laboratory Biomarker Analysis

Description: Correlative studies

Type: Other

Arm I (rituximab, bendamustine hydrochloride) Arm II (ibrutinib) Arm III (ibrutinib, rituximab)

Name: Quality-of-Life Assessment

Description: Ancillary studies

Type: Other

Arm I (rituximab, bendamustine hydrochloride) Arm II (ibrutinib) Arm III (ibrutinib, rituximab)

Name: Rituximab

Description: Given IV

Type: Biological

Arm I (rituximab, bendamustine hydrochloride) Arm III (ibrutinib, rituximab)


Primary Outcomes

Description: Log-rank statistics will be used to compare the PFS distributions of the different treatment arms. Progression is defined as any one of the following: an increase in number of blood lymphocytes by >= 50%, >= 50% increase in the products of at least 2 lymph nodes on 2 consecutive determination 2 weeks apart, >= 50% increase in the size of the liver/spleen, transformation to a more aggressive histology, progression of any cytopenia (i.e. decrease of hemoglobin [Hb] levels > 2g/dL). The methods of Kaplan and Meier will be used to estimate PFS for the treatment arms. For each of the planned comparisons, will assess the corresponding hazard ratios, and PFS medians along with their 95% confidence intervals.

Measure: Progression free survival (PFS)

Time: Time from study entry to the time of documented disease progression or death, assessed up to 10 years

Secondary Outcomes

Description: The Kaplan-Meier method will be used to estimate OS distributions in this chronic lymphocytic leukemia (CLL) population. OS will be measured from the date of registration to the date of the event (i.e., death) or the date of last follow-up to evaluate that event. Patients who are event-free at their last follow-up evaluation will be censored at that time point.

Measure: Overall survival (OS)

Time: From the date of registration to the date of death, assessed up to 10 years

Description: The Kaplan-Meier method will be used to estimate the rate of progression free survival at 2 years in this CLL population. Progression is defined as any one of the following: an increase in number of blood lymphocytes by >= 50%, >= 50% increase in the products of at least 2 lymph nodes on 2 consecutive determination 2 weeks apart, >= 50% increase in the size of the liver/spleen, transformation to a more aggressive histology, progression of any cytopenia (i.e. decrease of Hb levels > 2g/dL). Progression free survival time will be the time to either progression or death whichever occurs first.

Measure: Progression Free Survival at 2 years

Time: From the date of registration to the date of disease progression, assessed up to 10 years

Description: Duration of response is defined for all evaluable patients who have achieved an objective response (i.e., CR, nPR, PR) and will be calculated as the length of time from the date at which the patient's objective status is first noted to be a response to the date that progression or death is documented (if one has occurred) or to the date of last follow-up (for those patients who have not progressed or died). Complete response (CR) requires all of the following : absence of lymphadenopathy > 1.5 cm on physical exam/CT scan, no hepatomegaly or splenomegaly, no clonal B-cells in the blood, Normal CBC, bone marrow aspirate and biopsy must be normocellular for age. Partial response (PR) requires a >= 50% decrease in peripheral lymphocyte count from pre-treatment value, >= 50% reduction in lymphadenopathy, and/or ≥ 50% reduction in splenomegaly/hepatomegaly. Patients who fulfill the criteria of CR with exception of having bone marrow lymphoid CLL nodules will be considered a nodular PR (nPR)

Measure: Duration of response (complete response [CR], nodular partial response [nPR], and partial response [PR])

Time: From the date at which the patient's objective status is first noted to be a response to the date that progression or death is documented (if one has occurred) or to the date of last follow-up, assessed up to 10 years

Description: Complete response (CR) requires all of the following : absence of lymphadenopathy > 1.5 cm on physical exam/CT scan, no hepatomegaly or splenomegaly, no clonal B-cells in the blood, Normal CBC, bone marrow aspirate and biopsy must be normocellular for age. Partial response (PR) requires a >= 50% decrease in peripheral lymphocyte count from pre-treatment value, >= 50% reduction in lymphadenopathy, and/or ≥ 50% reduction in splenomegaly/hepatomegaly. Patients who fulfill the criteria of CR with exception of having bone marrow lymphoid CLL nodules will be considered a nodular PR (nPR). Estimated using the number of patients with the type of response of interest divided by the total number of patients randomized to that treatment arm. Corresponding exact binomial 95% confidence intervals for true response rates will be calculated.

Measure: Proportion of patients achieving any response to treatment (overall response rate [ORR] [partial response (PR) + nodular partial response (nPR) + complete response (CR)])

Time: Up to 10 years

Description: Complete response (CR) requires all of the following : absence of lymphadenopathy >1.5 cm on physical exam/CT scan, no hepatomegaly or splenomegaly, no clonal B-cells in the blood, Normal CBC, bone marrow aspirate and biopsy must be normocellular for age. Estimated using the number of patients with the type of response of interest divided by the total number of patients randomized to that treatment arm. Corresponding exact binomial 95% confidence intervals for true response rates will be calculated

Measure: Proportion of patients achieving a biopsy-proven complete response (CR)

Time: Up to 10 years

Description: Complete response (CR) requires all of the following : absence of lymphadenopathy >1.5 cm on physical exam/CT scan, no hepatomegaly or splenomegaly, no clonal B-cells in the blood, Normal CBC, bone marrow aspirate and biopsy must be normocellular for age. Patients who fulfill the criteria of CR with exception of having bone marrow lymphoid CLL nodules will be considered a nodular PR (nPR). Estimated using the number of patients with the type of response of interest divided by the total number of patients randomized to that treatment arm. Corresponding exact binomial 95% confidence intervals for true response rates will be calculated

Measure: Complete and nodular partial response (nPR) rate

Time: Up to 10 years

Description: Estimated using the number of patients who achieve minimal residual disease divided by the total number randomized to that treatment arm. Corresponding exact binomial 95% confidence intervals for MRD rates will be calculated.

Measure: Proportion of patients who attain minimal residual disease (MRD) negative status

Time: Up to 10 years

Description: Will be assessed.

Measure: Proportion of patients who experience grade 3 or higher non-hematologic toxicities

Time: Up to 10 years

Other Outcomes

Description: Assessed using the Older Americans' Resources and Services Multidimensional Functional Assessment Questionnaire, Activities of Daily Living, Medical Outcomes Study physical functioning, Karnofsky performance status rated by a health care professional, Karnofsky performance status rated by the patient, timed "Up and Go", and number of falls in the last six months.

Measure: Geriatric functional status (optional)

Time: Up to 10 years

Purpose: Treatment

Allocation: Randomized

Crossover Assignment


There are 2 SNPs

SNPs


1 rs172378

To assess whether complement component 1, q subcomponent, A chain (C1QA) polymorphism (rs172378) is correlated with MRD status, CR rate, rapidity of response, and PFS.


2 rs396991

To assess whether the Fc fragment of IgG, low affinity IIIa, receptor (CD16a) (FCGR3A) polymorphism (rs396991) is correlated with depth of response (MRD status) to ibrutinib plus rituximab after 6 cycles, with secondary endpoints CR rate, rapidity of response, and progression-free survival (PFS).



HPO Nodes


HPO:
Chronic lymphatic leukemia
Genes 8
SAMHD1 RNASEH2B ADAR RNASEH2A IFIH1 RNASEH2C TREX1 PIK3R1
Leukemia
Genes 125
MPL RNASEH2B KRAS NPM1 TET2 MYD88 TSR2 RPL26 RPL27 TREX1 EFL1 PIGL SCN11A FLT3 PMS2 RPL35A EVC2 ABL1 CEBPA RARA NRAS WAS WIPF1 ATRX SH2B3 PDGFRA RB1 RNASEH2A PDGFRB CALR ARHGAP26 SH3GL1 RPS7 RPS10 NUMA1 GATA1 GATA2 RPS15A APC NSD1 ETV6 TCIRG1 DNAJC21 EVC SRP54 RPS17 NBN RPS19 SAMHD1 MSH2 RPS24 NUP214 RPS26 RPS27 RPS28 RPS29 MLLT10 RUNX1 XRCC4 CBFB CBL BCR ADAR TRIP13 ADA2 NSUN2 CREBBP PICALM GFI1 F13A1 F13B FANCA FANCC BLM FANCD2 FANCE NUTM1 JAK2 IFIH1 TYROBP MSH6 FANCG LIG4 PTPN11 SAMD9L THPO NF1 STS PIGA BRCA2 DYNC2LI1 PIK3CA SBDS GLI1 PIK3R1 BRD4 SETBP1 RNASEH2C LPP BUB1 BUB1B SCN9A SCN10A TREM2 MLF1 MLH1 ELANE DKC1 ATM HAX1 RPL35 GNB1 BUB3 CEP57 TAL1 KIT TAL2 RPL5 EP300 TP53 RPL11 KIF11 RPL15 DNMT3A RPL18
Lymphoid leukemia