SNPMiner Trials by Shray Alag


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Report for SNP rs861529

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There is one clinical trial.

Clinical Trials


1 Randomized Study of Personalized Melphalan Dosing in the Setting of Autologous Transplant

This randomized phase II trial studies the side effects and how well melphalan hydrochloride works in treating patients with multiple myeloma that has come back or does not respond to treatment. Drugs used in chemotherapy, such as melphalan 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.

NCT03328936 Hematopoietic Cell Transplantation Recipient Recurrent Plasma Cell Myeloma Refractory Plasma Cell Myeloma Other: Laboratory Biomarker Analysis Drug: Melphalan Hydrochloride Drug: Melphalan Hydrochloride Other: Pharmacological Study
MeSH: Multiple Myeloma Neoplasms, Plasma Cell
HPO: Multiple myeloma

Will determine the parameter accuracy and precision of the newly integrated PK/PD model for absolute neutrophil count, mucositis, tachyarrhythmias, and disease progression.. XRCC1 rs25487 and XRCC3 rs861529 variant alleles.

Will use Cox survival analysis, measure progression free survival of patients with XRCC1 rs25487 and XRCC3 rs861529 variant alleles compared to wild type.. Inclusion Criteria: - Patient must have relapsed or refractory myeloma that fits or did fit IMWG diagnostic criteria for multiple myeloma; patients with AL amyloidosis and polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) are excluded; measurable disease is not required - Patient undergoing autologous transplant as part of first line therapy - All races and ethnic groups are eligible for this study - Patients must also have an adequate autologous graft as defined as a cryopreserved peripheral blood stem cell (PBSC) graft containing > 2 x 10^6 CD34+ cells/kg patient weight - Eastern Cooperative Oncology Group (ECOG) performance status < 2 (Karnofsky > 60%) is required for eligibility; those patients with lower performance status based solely on bone pain secondary to multiple myeloma are eligible - Absolute neutrophil count (ANC) > 1000/uL - Platelet count > 50,000 - Transfusion independent - Total bilirubin < 1.5 mg/dL - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x the institutional upper limit of normal - Left ventricular ejection fraction >= 40% - Carbon monoxide diffusing capability (DLCO) > 50% predicted - Forced expiratory volume in 1 second (FEV1) > 50% predicted - Forced vital capacity (FVC) > 50% predicted - Ability to understand and willingness to sign a written informed consent document - Females of childbearing potential (FCBP) must not be pregnant as per institutional standard; if no institutional standard exists, then patients must have a negative serum or urine pregnancy test prior to transplant; a female of childbearing potential (FCBP) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months) Exclusion Criteria: - Patients who are receiving any other anti-myeloma investigational agents - Uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, myocardial infarction in the preceding 6 months, or psychiatric illness/social situations that would limit compliance with study requirements - Pregnant women are excluded from this study; breastfeeding should be discontinued - Patients with a "currently active" second malignancy that, in the opinion of the principal investigator, will interfere with patient participation, increase patient risk, shorten survival to < 1 year, or confound data interpretation - Concurrent use of complementary or alternative medicines that in the opinion of the principal investigator would confound the interpretation of toxicities and/or antitumor activity of the study drug Inclusion Criteria: - Patient must have relapsed or refractory myeloma that fits or did fit IMWG diagnostic criteria for multiple myeloma; patients with AL amyloidosis and polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) are excluded; measurable disease is not required - Patient undergoing autologous transplant as part of first line therapy - All races and ethnic groups are eligible for this study - Patients must also have an adequate autologous graft as defined as a cryopreserved peripheral blood stem cell (PBSC) graft containing > 2 x 10^6 CD34+ cells/kg patient weight - Eastern Cooperative Oncology Group (ECOG) performance status < 2 (Karnofsky > 60%) is required for eligibility; those patients with lower performance status based solely on bone pain secondary to multiple myeloma are eligible - Absolute neutrophil count (ANC) > 1000/uL - Platelet count > 50,000 - Transfusion independent - Total bilirubin < 1.5 mg/dL - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x the institutional upper limit of normal - Left ventricular ejection fraction >= 40% - Carbon monoxide diffusing capability (DLCO) > 50% predicted - Forced expiratory volume in 1 second (FEV1) > 50% predicted - Forced vital capacity (FVC) > 50% predicted - Ability to understand and willingness to sign a written informed consent document - Females of childbearing potential (FCBP) must not be pregnant as per institutional standard; if no institutional standard exists, then patients must have a negative serum or urine pregnancy test prior to transplant; a female of childbearing potential (FCBP) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months) Exclusion Criteria: - Patients who are receiving any other anti-myeloma investigational agents - Uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, myocardial infarction in the preceding 6 months, or psychiatric illness/social situations that would limit compliance with study requirements - Pregnant women are excluded from this study; breastfeeding should be discontinued - Patients with a "currently active" second malignancy that, in the opinion of the principal investigator, will interfere with patient participation, increase patient risk, shorten survival to < 1 year, or confound data interpretation - Concurrent use of complementary or alternative medicines that in the opinion of the principal investigator would confound the interpretation of toxicities and/or antitumor activity of the study drug Hematopoietic Cell Transplantation Recipient Recurrent Plasma Cell Myeloma Refractory Plasma Cell Myeloma Multiple Myeloma Neoplasms, Plasma Cell PRIMARY OBJECTIVES: I. Identify whether targeting approximate (approx.)

V. Measure allele and genotype frequencies of variants, as well as gene expression of XRCC1 rs25487 and XRCC3 rs861529.

Primary Outcomes

Description: Complete response will be defined as complete response + stringent complete response according to the International Myeloma Working Group Uniform response criterion. Will be calculated with an exact 95% confidence interval, both within arms and across arms.

Measure: Complete response proportion

Time: At 90 days

Secondary Outcomes

Description: Will assess melphalan-related toxicities (possibly, probably, or definitely related to high dose melphalan) including the incidence of grade 3/4 mucositis, grade 3/4 bacteremia, length of inpatient stay, duration of severe neutropenia (absolute neutrophil count < 500), duration of severe thrombocytopenia (Platelet < 20K), and proportion with tachyarrhythmias (e.g. atrial fibrillation with rapid ventricular rate).

Measure: Incidence of melphalan hydrochloride-related toxicities

Time: Up to 3.5 years

Description: Will be assessed by standard next generation sequencing.

Measure: Minimal residual disease negative proportions

Time: Pre-transplant

Description: Will be assessed by standard next generation sequencing.

Measure: Minimal residual disease negative proportions

Time: up to 1 year

Description: Will be assessed.

Measure: Overall survival

Time: time from randomization to death, assessed up to 3.5 years

Description: Will be assessed.

Measure: Progression free survival

Time: Time from transplant to death, clinical relapse, progressive disease, and death in all treated patients, assessed up to 3.5 years

Description: Will be assessed.

Measure: Time to biochemical relapse

Time: Time from start of melphalan hydrochloride until the earliest of the following time points: progressive disease, clinical relapse, or relapse from complete response, assessed up to 3.5 years

Description: Will be assessed.

Measure: Time to progression

Time: Time from start of melphalan hydrochloride until the criteria for disease progression are met, assessed up to 3.5 years

Other Outcomes

Description: Will compare DNA damage repair efficiency in patients that have minimal response to induction and high dose melphalan hydrochloride (partial response or less) compared to those that are sequencing minimal residual disease negative.

Measure: Deoxyribonucleic acid (DNA) damage repair

Time: Up to 3.5 years

Description: Will create a multivariate linear regression model that includes each patient?s IC50, DNA repair gene single nucleotide polymorphism (SNP) presence or absence, and revised Multiple Myeloma International Staging System with progression free survival as the outcome.

Measure: Half maximal inhibitory concentration (IC50)

Time: Up to 3.5 years

Description: Will compare the prediction accuracy of melphalan hydrochloride pharmacokinetics using the test dose versus the current PK model. Test the use of aspects of test dose PK as a covariate in the current high dose melphalan hydrochloride prediction model.

Measure: Melphalan hydrochloride pharmacokinetics (PK) parameters

Time: Within 2 hours prior to start of melphalan hydrochloride infusion and at 5, 30, 45, and 60 minutes, and 3 and 6 hours

Description: Will correlate with progression free survival.

Measure: p53 messenger ribonucleic acid

Time: Up to 3.5 years

Description: Will correlate with progression free survival.

Measure: Phosphorylated TP53

Time: Up to 3.5 years

Description: Will determine the parameter accuracy and precision of the newly integrated PK/PD model for absolute neutrophil count, mucositis, tachyarrhythmias, and disease progression.

Measure: PK/pharmacodynamics (PD) model

Time: Up to 3.5 years

Description: Will use Cox survival analysis, measure progression free survival of patients with XRCC1 rs25487 and XRCC3 rs861529 variant alleles compared to wild type.

Measure: XRCC1 rs25487 and XRCC3 rs861529 variant alleles

Time: Up to 3.5 years


HPO Nodes


Multiple myeloma
Genes 3
LIG4 CCND1 GBA