Diseases and Abnormalities at or Before Birth

All Conditions

Neoplasms

Blood and Lymph Conditions

Immune System Diseases

Heart and Blood Diseases

Rare Diseases

Congenital Abnormalities

Lymphoma

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Lymphosarcoma

Investigators will select the first drug listed in the tumor analysis report for the first mutation listed in the tumor analysis report. However, If the subject has a medical contraindication to the first listed drug (according to the drug label) or the first listed drug cannot be obtained for the patient, the study team will select the next drug presented by the tumor sequencing report. Patients receive targeted therapy based on next generation sequencing report. Cycles repeat every 2, 4, or 6 weeks in the absence of disease progression or unacceptable toxicity.

Treatment will be administered on an inpatient or outpatient basis based on the type of medication selected. The investigatory will administer the drug as directed in the FDA approved label.

Investigational Agent

Supportive care regimens will vary depending on the type of drug that will be administered at the treating investigator's discretion.

Supportive Care Regimens

1) Next Gen Sequencing report obtained as Standard of Care within the past 12 months of enrollment date will be used. If more than one report exists in this time period, the most recent report will be used.

Next Gen Sequencing Report

Stefan Grant, MD

The goal of the current pragmatic trial is to evaluate the impact of a simple method of selecting a treatment approach for identified mutations on participants' progression free survival (PFS). The study also intends to collect information on barriers that investigators encounter when prescribing treatment options using the Next Generation Sequencing (NGS) reports. Additionally, patients' quality of life will be measured before, after, and during treatment.

Patients will be followed until death for monitoring survival study endpoints.

Primary Objective:

• To estimate the progression-free ratio, as defined by the progression-free survival time on study treatment divided by the progression-free survival time on the last treatment received by patient, for an identified actionable mutation, who will be treated with an off-label treatment off label therapy based on a simplified selection methodology using the Next Generation Sequencing results.

Secondary Objectives:

* To estimate patient response rate on off-label treatments for actionable mutations based on Next Generation Sequencing results.
* To estimate overall survival (OS) for patients treated with off-label treatments for actionable mutations based on Next Generation Sequencing results.
* To describe the safety of using off-label or other experimental treatments for patients with actionable mutations based on Next Generation Sequencing results.

Exploratory Objectives:

* To describe health related quality of life in patients undergoing off-label treatment targeting genetic mutations, as measured by the PROMIS-29 Overall Health-Related Quality of Life, Including 4-Item Anxiety Subscale.
* Using the Satisfaction with Medical Decision Scale, to describe patient satisfaction with decision to pursue off-label treatment.
* To identify types of actionable mutations with available targeted treatment occurring in cancer patients.
* To characterize the historical treatment regimens for these patients relative to the targetable mutation.
* To describe patient clinical and demographic characteristics of those with actionable mutations based on Next Generation Sequencing results.
* To identify barriers to treatment based on Next Generation Sequencing results.

Precision Medicine for Patients With Identified Actionable Mutations

Precision Medicine for Patients With Identified Actionable Mutations at Wake Forest Baptist Comprehensive Cancer Center (WFBCCC): A Pragmatic Trial-

Estimation of progression-free ratio defined as the duration of time from start of treatment to the time of progression divided by the duration of time from the last treatment received pre-trial to the time of progression on that treatment. The median progression-free ratio will be estimated with the range and a two-sided Wilcoxon Signed Rank test will be calculated to see if the progression free survival ratio is different from 1.0. This trial is powered to detect differences in the progression-free ratio for those with actionable mutations identified by NGS results and then treated with a targeted therapy. A hypothesized PFS ratio larger than 1.3 would suggest that the targeted therapy is doing better than the previous treatment received (not targeted), and we assume a null hypothesis PFS ratio of 1.0 (no difference).

Overall survival will be displayed using Kaplan-Meier curves with median survival times and 95% confidence intervals.

Adverse events will be summarized in incidence tables by type and grade severity for all patients and presented by type of treatment received.

Response rate will be estimated for all patients with corresponding 95% confidence intervals.

National Cancer Institute (NCI)

Wake Forest University Health Sciences

Teclistamab

Jessica Vandermark

Mercedes Martillo

Hearn J Cho, MD, PhD

This trial is an adaptive platform trial. The structure of the protocol allows the trial to evolve over time. Multiple investigational arms will be included within the trial under a Master Protocol (MP). These investigational arms may be added as appendices at different times depending on whether they are trial-ready and whether accrual in the trial will support another arm. Accrual to an arm will terminate in accord with the arm's appendix to the Master Protocol.

The purpose of this proposed structure is to support the recurrent research challenge of efficiently evaluating what is the best therapy for a particular patient.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Precision Medicine for Patients With Identified Actionable Mutations	NCT04111107	Solid Tumor Lymphoma Multiple Myelom... Malignant Neopl... Mutation Abnorm...	Investigational... Supportive Care... Next Gen Sequen...	18 Years -	Wake Forest University Health Sciences
Horizon Adaptive Platform Trial Evaluating Therapies in RRMM	NCT06171685	Relapse Multipl... Refractory Mult...	Teclistamab Investigational...	18 Years - 99 Years	Multiple Myeloma Research Consortium

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