Autologous Bone Marrow Transplantation - Blog Science Connections

Proposed International Adult Lymphoma Study 329
replicates the BEAM regimen with only one modification. Because melphalan
is still an experimental drug in the United States, we decided to substitute
the classic cyclophosphamide (35 mg/kg x 4).
THE PROJECTED INTERNATIONAL STUDY: A SUMMARY
The projected international study will be a phase III randomized study of
involved-field XRT, high-dose chemotherapy consolidation (BEAC), and
ABMT therapy compared with maintenance chemotherapy and involved-field
XRT in patients totally responding to DHAP therapy at the time of first or
second relapse (in or off frontline therapy) (Fig 10). The objectives are to
compare intensive therapy with or without ABMT rescue in patients with SRs,
to show at least a 20% improvement in disease-free survival rates with ABMT 2
years after randomization, and to evaluate the toxicity and mortality
associated with each approach.
Patient eligibility standards will be the following: 1) patients must have
relapsed diffuse intermediate- and high-grade lymphomas and must be
adults who are less than 60 years old; 2) patients must have been previously
treated with a doxorubicin-containing regimen or COMLA (Cytoxan, vincristine,
methotrexate, Leucovorin rescue, ara-C); 3) patients must not have CNS
or bone marrow involvement at relapse; 4) only patients who have previously
reached a first CR on the induction regimen (i.e., a true relapse) are eligible for
this protocol; and 5) only patients with a first or second relapse will be
admitted to the study group.
The international study is expected to enroll 142 patients who will be
randomized into two groups of 71 each. A 3-year inclusion period is scheduled
for reaching this sample size. Statistical parameters will be the following
(two-sided test): a = 5% and j8 = 20%.
There will be two phases—the preinclusion and inclusion phases—to the
treatment plan. In the preinclusion phase (with all patients admitted with an
intention to treat), two courses of DHAP will be administered (see Table 2),
and then patients whose disease responds to therapy even in relapse (SRs)
will be randomized into two groups. After randomization, one group will
receive involved-field XRT, high-dose BEAC chemotherapy (Table 3), and
Table 2. DHAP Protocol
Agent Dose Day Administration
Dexamethasone 40 mg 1-4 15-min bolus i.v.
Cisplatin 100 mg/m2 1 24-hr continuous
infusion i.v.
Cytarabine 4 g/m2 2 2 g/m 2 3-hr i.v.
every 12 hr x 2