The major treatment-related toxicities in TT3 pertained to the high-dose melphalan 200mg/m2 (MEL200)-based tandem transplant approach, consisting of mucosal and other toxicities.~For the TT4 trial, we are proposing to compare standard TT3 (S-TT3) to TT3-Lite (L-TT3). L-TT3 will employ various strategies aimed at improving the therapeutic Index of S-TT3 by reducing toxicities while maintaining the superior results reported for S-TT3 in terms of frequency and duration of CR, EFS, and. The following strategies will be utilized in L-TT3:~Applying only 1 instead of 2 cycles of induction and consolidation therapy prior to and after tandem transplant. This is supported by the well known association between prior exposure to mucotoxic therapies4, 5 and worse post-transplant mucositis, particularly when etoposide is used in the mobilizing regimen6 such as in VDTPACE.~Note: Randomization has been discontinued and accrual is closed to the L-TT3 arm. This trial is currently enrolling as a single-arm trial for patients to receive S-TT3.
Toward improving the therapeutic index of standard TT3 (S-TT3), the investigators will employ a randomized Phase III trial design to determine whether S-TT3 treatment-related toxicities can be reduced by 50% in TT3-Lite (L-TT3).~Note: Randomization has been discontinued and accrual is closed to the L-TT3 arm. This trial is currently enrolling as a single-arm trial for patients to receive S-TT3.