ANCO ASH 2005 ReviewANCO ASH 2005 Review Acute Leukemias Acute Leukemias

Feb 22, 2006Feb 22, 2006

Charles LinkerCharles Linker MDMD

Abstract # 43Abstract # 43Mini-allo for AMLMini-allo for AML

Herr et alHerr et alEBMT ReviewEBMT Review

Mini-allo for AMLMini-allo for AMLEBMT RegistryEBMT Registry

n = 204Age 58 (median)Sib and MUD donorsRegimen - Flu/Bu, Flu/TBIFU 13mo

1-yr TRM 15%1-yr Rel 34% 1-yr LFS 50%1-yr OS 62%

Abstract # 47Abstract # 47Mini-allo for AMLMini-allo for AML

Shimoni et alShimoni et alTel Hashomer, IsraelTel Hashomer, Israel

Mini-allo AMLMini-allo AMLIsraelIsrael

n = 67Age > 55Sib and MUD donorsRegimen - Flu/Bu FU 22mo

2-yr TRM 8%2-yr OS 47%

If CR1: 2-yr OS 80%, TRM 0%

CALGB 100103

Phase II Study of mini-allo for AML CR1, age > 60

Study Chair: Steve DevineStudy Chair: Steve DevineCTN co-chair: Sergio GiraltCTN co-chair: Sergio Giralt

CALGB 100103Background - 1

• Poor results of chemotherapyPoor results of chemotherapy• No signs of progress in chemotherapyNo signs of progress in chemotherapy• New approaches are warrantedNew approaches are warranted

CALGB 100103CALGB background data

• Analysis of 600 CALGB AML age > 60 with Analysis of 600 CALGB AML age > 60 with cytogeneticscytogenetics

CR 50%CR 50%5-year OS 7% !!!5-year OS 7% !!!Cytogenetics predictive of outcomeCytogenetics predictive of outcome

AML CR1, age > 60DFS by Cytogenetics

Time (Years)

Probability of Remaining Disease-Free

0 5 10 15

0.0

0.2

0.4

0.6

0.8

1.0

<5 abnormalities (n=273)

>= 5 abnormalities (n=23)

P<0.001

< 5 Abnormalities

P<0.001

5 Abnormalities

AML CR1, age > 60OS by Cytogenetics

AML CR1, age > 60OS by Age

CALGB 100103Background - 2

• Results in best group are still poor (n = 276)Results in best group are still poor (n = 276)CR1CR1Age 60-75Age 60-75Receive first consolidation on randomized trialReceive first consolidation on randomized trial

• 2-year DFS 24%2-year DFS 24%• 3-year DFS 17%3-year DFS 17%

CALGB 100103Eligibility - 1

• AML CR1AML CR1Prior MDS, t-AML allowedPrior MDS, t-AML allowed<< 2 cycles induction 2 cycles induction<< 2 courses consolidation 2 courses consolidation<< 6 months in CR1 6 months in CR1exclude APL, prior MPDexclude APL, prior MPD

• Age 60-74Age 60-74• Matched sibling or 10/10 MUD donorMatched sibling or 10/10 MUD donor

CALGB 100103Eligibility - 2

• PS 0 - 2PS 0 - 2• Adequate organ functionAdequate organ function

DLCODLCO > > 40% 40%EF EF >> 30% 30%Creatinine clearanceCreatinine clearance > > 40 40Bili < 2.0Bili < 2.0AST < 3x normalAST < 3x normal

CALGB 100103 Preparative Regimen

• Fludarabine 30 mg/m2 x 5Fludarabine 30 mg/m2 x 5 days -7 to -3days -7 to -3• Busulfan 0.8 mg/kg IV x 8Busulfan 0.8 mg/kg IV x 8 days -4 to -3days -4 to -3• Thymoglobulin 2.5 mg/kg x 3Thymoglobulin 2.5 mg/kg x 3 days -4 to -2days -4 to -2• Stem cell infusionStem cell infusion day 0day 0

CALGB 100103 GVH Prophylaxis

• TacrolimusTacrolimus day - 2 to +90day - 2 to +90• MTX 5 mg/m2MTX 5 mg/m2 days, +1, 3, 6, 11days, +1, 3, 6, 11

• Taper tacTaper tac day +90 to +150/+180 day +90 to +150/+180

CALGB 100103 Statistics

• Primary objective 2-year DFS Primary objective 2-year DFS >> 35% 35%90% power to exclude DFS < 20%90% power to exclude DFS < 20%

• Accrual goal = 61Accrual goal = 61• Stopping rules for TRMStopping rules for TRM

Assume true TRM 20%Assume true TRM 20%Unacceptable TRM 40%Unacceptable TRM 40%

CALGB 100103

• Currently active in CALGB Currently active in CALGB sib donors onlysib donors only

• Amendment in processAmendment in processAdd CTNAdd CTNAdd MUDAdd MUD

Mini-allo for AML, age > 60

• Currently treatments work poorlyCurrently treatments work poorly• Mini-allo is feasibleMini-allo is feasible• Several pilot studies show DFS > 40%Several pilot studies show DFS > 40%• Deserves testing in Group settingDeserves testing in Group setting• CALGB 100103 is last chance for USA studyCALGB 100103 is last chance for USA study

Abstract # 146Abstract # 146Ph+ ALLPh+ ALL

Dellanoy et alDellanoy et alGRALL, FranceGRALL, France

Ph+ ALL,age > 55Ph+ ALL,age > 55TreatmentTreatment

• Pre-phasePre-phasePrednisone x 1 week

• InductionInduction CyDVPImatinib 600 x 2 mo

• ConsolidationConsolidation10 blocks of chemo

2 x 2 mo imatinib • CNS-PCNS-P

i.t. mtx + cranial RT

Ph+ ALL, age > 55Ph+ ALL, age > 55ResultsResults

N = 30Age 66 (58 - 78)FU 15moCR 20/29 ( vs 6/21 historical control)1-yr OS 71% (11% control)1-yr EFS 57% (5% control)

ASCT for high-risk ALLProtocol 9501 & SOC

10864200.0

0.2

0.4

0.6

0.8

1.0

EFS 44%

10/25/05YEARS

Protocol 9501 SOC for Ph+Effect of Imatinib

10864200.0

0.2

0.4

0.6

0.8

1.0

Imatinib EFS 71%

pre-Imatinib EFS 20%

10/25/05YEARS

Ph+ ALLPh+ ALLRole of ImatinibRole of Imatinib

• Plays major role in inductionPlays major role in inductionSafe to combine with chemotherapySafe to combine with chemotherapyIncreases remission rateIncreases remission rate

• Encouraging results post-remissionEncouraging results post-remission• May play role in transplantMay play role in transplant

Allo transplant is treatment of first choicePatients get to transplant in remission May reduce relapse rateASCT being tested in CALGB 10001

May allow PCR neg stem cells for ASCT

Abstract # 150Abstract # 150Nelarabine for T-ALLNelarabine for T-ALL

Goekbuget et alGoekbuget et alGMALL, GermanyGMALL, Germany

CALGB 19801CALGB 19801De Angelo et alDe Angelo et al

ASH #743 (2002)ASH #743 (2002)• Eligibility

T-ALL or T-LLRelapse or refractory

• TreatmentNelarabine (GW 506U) 1.5g/m2 days 1, 3, 5q3 weeks x 2 cyclesResponders may get additional 2 cycles

• Results10/38 CR (26%)MDCR 10mo1-yr DFS 40%

NelarabineNelarabinePatients and TreatmentPatients and Treatment

• n = 53• Age 31 (19 - 81)• Disease category:

First relapse 36Second relapse 7Relapse after transplant 7Refractory 3

• Treatment:Nelarabine 1.5g/m2 days 1, 3, 5

NelarabineNelarabineResultsResults

25/53 CR (47%)19/25 Cr go to transplantOS 16%OS of CR 27%

Nelarabine for T-ALLNelarabine for T-ALL

• Important new agentImportant new agent• Good choice for relapseGood choice for relapse• Should be tested up frontShould be tested up front