“INVESTIGATORY” TRANSPLANTS Helen Heslop Roy Jones

Pivotal Question Does participation in early-phase, therapeutically-oriented clinical trials have independent prognostic significance for OUTCOME? Motivation: avoid punishing centers conducting high-risk research if outcomes are inferior as a result

Examples of Trials “Near Myeloablative” preparative regimen for myeloma patients Minimal intensity preparation for high risk tumors Transplant for “new” diseases Second allotransplants Strategies to reduce risk of relapse in high risk patients

Hypothesis Participation in an early-phase therapeutically-directed clinical trial is an independently negative prognostic factor –Patients participating in these studies are at higher risk for adverse outcomes than those receiving standard of care treatments –Already-collected patient variables do not adequately describe this risk

Operational Questions How do we uniformly identify these trials and patients participating in them? How do we acquire and use the information?

Proposal Identify research trials and later identify patients participating in them. Identify research participation as a single data collection element reportable to the SCTOD (dichotomous variable) Analyze independent effect on outcome using established statistical techniques, likely in a pilot fashion.

Identification of Research Trials Simple protocol-specific questionnaire to be filled out and scored by centers. Y/N reply to a provisional data element included in FormsNet based on a given patient’s research study participation –Intent to treat Analysis by SCTOD staff Formal adoption as a data element only if hypothesis is accepted.

Content of Trial Questionnaire IRB approval: Y Peer-reviewed, published, reproducible: N Correct answer required Therapeutic intent: Y Use of non-standard cell products: Y Toxicity mitigation of high-risk therapy: Y Older or high-comorbidity patients: Y One of four must be yes

Questions or Comments?

Screening Questions Is the treatment protocol IRB-approved? Has the protocol treatment been published in the peer-reviewed literature in sufficient detail to be reproduced? Answer to Q1 must be YES Answer to Q2 must be NO

Screening Questions Is the protocol designed to treat malignancy, genetic disease, or aplastic anemia? Does the protocol propose the use of unrelated cell products outside of the specifications in Q#2? Is the protocol designed to mitigate toxicity where the estimate of fatal toxicity for the protocol exceeds 30%? Is the protocol designed to enroll older patients (allos >60, autos >65) or patients with high comorbidity scores (HCT-CI>2)? At least one must be YES