INCTR

1
African Burkitts Lymphoma Strategy Group Report

• Presented by Twalib Ngoma for
• M.A. Durosinmi
• Obafemi Awolowo University Teaching Hospitals
  Complex, Ile-Ife, Nigeria

2
The Journey So FarMeetings Held to Date

• 1st June 2002
• Discuss on-going activities in the treatment of
  African BL in sub-Saharan Africa
• Determine interest in the development of a
  collaborative program for the study of this
  disease
• Determine interest in the development of a common
  treatment protocol for African BL

3
The Journey So FarMeetings Held to Date

• 6 - 7th Dec 2002
• Develop a strategy for characterization and
  treatment
• Standardize COM regimen
• Standardize IT therapy
• Develop gene expression studies
• Discuss ethical considerations
• Plan data management
• Plan strategies to improve patient follow-up

4
The Journey So FarMeetings Held to Date

• 31st May 2003
• Review progress with standardized COM regimen
• Finalize treatment protocol for African BL
• Discuss gene expression studies
• Discuss serum EBV DNA studies

5
The Journey So FarMeetings Held to Date

• Protocol Implementation Meeting
• 12 13th August 2004 Dar es Salaam, Tanzania
• Review of the protocol document
• In-depth review of the case report forms data
  management procedures
• Decide protocol activation date
• Discuss data quality assurance plan
• Discuss potential new studies

6
Background Experience with Standard COM at
Ile-IfePatient Characteristics
7
Background ExperienceStage and Risk Group
8
Background ExperienceSites of Disease
9
Background ExperienceResponse
10
Problems Encountered During Pilot of COM

• 12/32 treated patients completed planned
  treatment (others unable to pay for therapy)
• 1 patient died of neutropenic sepsis
• Reversible myelosuppression noted in many
  patients

11
Problems Encountered During Pilot of COM

• 4 deaths (2, PD, 1, early relapse and 1, sepsis)
• 28/32 treated patients lost to follow-up
• All drugs for second-line treatment were not
  available during the pilot phase

12
Comments Pilot of COM

• CR rate superior with standardized COM
• Drug toxicity is minimal
• Anticipated mucositis did not occur
• No tumor lysis with hydration regimen
• Price is affordable (USD 160 for 6 cycles) and
  drugs are available
• To avoid default, it will be necessary to provide
  drugs for treatment

13
Protocol INCTR 03-06

• Title The Treatment and Characterization of
  Burkitts Lymphoma in Africa
• 5 participating institutions in 4 countries
• Anticipated rate of accrual 180 240 eligible
  patients/year

14
Participating Institutions in Africa

• KENYA
• Kenyatta National Hospital, University of
  Nairobi, Nairobi (Dr Jessie Githanga)
• NIGERIA
• University College Hospital, Ibadan (Dr Yetunde
  Akenova)
• Obafemi Awolowo University Teaching Hospitals
  Complex, Ile-Ife (Dr MA Durosinmi)

15
Participating Institutions in Africa

• TANZANIA
• Ocean Road Cancer Institute, Dar es Salaam (Dr
  Twalib Ngoma)
• UGANDA
• Mbarara University of Science and Technology,
  Mbarara (Dr Julius Kiwanuka)

16
INCTR Personnel

• Medical Advisors
• Ian Magrath
• Ama Rohatiner
• Aziza Shad
• Study Coordination and Data Management
• Melissa Adde
• Lolita Lantican

17
Protocol Design

• Eligibility Criteria
• Diagnosis BL, Burkitt-like and Large B cell
  lymphoma
• Patients aged gt 2 - lt 60 years
• No history of prior treatment

18
Protocol Design

• First-Line Treatment
• Low Risk Arm
• Single extra-abdominal mass lt 10 cm
• High Risk Arm
• All other patients not meeting low risk
  definition
• Second-Line Treatment
• Failures of First-Line Treatment

19
First-Line Treatment

• Low Risk Arm
• 3 cycles of treatment
• Administered every 14 days
• High Risk Arm
• 6 cycles of treatment
• CNS disease IT therapy x 6 cycles
• No CNS disease IT therapy x 3 cycles

20
First-Line Treatment
21
Second-Line Treatment

• Criteria for Second-Line Treatment
• Failures of First-Line Treatment
• NR/PD
• No CR after 2 cycles
• Early relapse (within 3 months)
• Total 4 cycles
• Administered every 21 days

22
Second-Line Treatment
23
Other Elements to be Added

• Molecular profiling of African BL versus BL in
  Europe
• Comparison with clinical characteristics
• Comparison with treatment outcome
• EBV DNA in serum
• Comparison with clinical stage
• Evaluation as a prognostic indicator (relapse)
• Tumor and serum samples to be collected pending
  development of funding

24
Activation of Protocol INCTR 03-06

• Data managers in 4/5 participating centers
• Assist with patient monitoring follow up
• Data collection
• Patient accrual began 15th Aug 2004
• Total patients accrued to date 6
• Total patients not entered to date 8 (6, not
  eligible due to prior treatment 1, refused 1,
  died before diagnosis confirmed)

25
Summary

• Ethical approval
• INCTR ERC and 4/5 participating institutions
• Protocol Implementation Meeting, Aug, 2004
• Infrastructure for data management, including
  patient follow-up in place in most participating
  institutions
• Patient accrual has begun
• Support for costs of treatment are being pursued

26
Appreciation

• Members of the African BL Strategy Group
• Colleagues in Department of Haemotology and
  Paediatrics, OAUTHC, Ile-Ife

27
THANK YOU FOR YOUR ATTENTION