Lentivirus Transduced Acute Myeloid Leukaemia Blasts Expressing B7.1 (CD80) and IL-2

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and tolerability of an 'AML Cell Vaccine' in patients with poor prognosis acute myeloid leukaemia (AML).

Official Title
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A Phase I Study of Lentivirus Transduced Acute Myeloid Leukaemic Cells (AML) Expressing B7.1 (CD80) and IL-2 for the Potential Enhancement of Graft Versus Leukaemia(GvL) Effect in Poor Prognosis AML

Conditions
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Leukemia, Myeloid, Acute

Intervention / Treatment
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* Biological: RFUSIN2-AML1
* Biological: Donor leukocyte infusion (DLI)
* Biological: RFUSIN2-AML1 and donor leukocyte infusion
* Biological: RFUSIN2-AML1 and donor leukocyte infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of AML defined according to the WHO classification Age ≥ 18 years New presentation or relapsed AML Patients must be able to give written informed consent Failure to enter complete morphological remission (>5% bone marrow AML cells) or persistence of cytogenetic abnormality following intensive combination chemotherapy At day+100 post-transplant HIV negative No GvHD No continuing use of immunosuppressive drugs Absence of active systemic fungal or viral infection including HTLV-1, hepatitis B or C. Adequate renal and liver function confirmed by: creatinine clearance >30mls/min; bilirubin <3.0 x upper limit of normal; AST <3.0 x upper limit of normal; prothrombin time <2.0 x upper limit of normal. Performance status of 1 or less by ECOG criteria or >80% by the Karnovsky score Patient must provide written informed consent and be willing to comply for the duration of the study. Life expectancy >36 weeks Women of childbearing potential (WCBP) must have a negative serum or urine pregnancy test within 10 - 14 days and again within 24 hours of starting the study. In addition, sexually active WCBP must agree continued abstinence from heterosexual intercourse or to use adequate contraceptive methods starting 4 weeks prior to the initiation of therapy (see appendix G for pregnancy testing and birth control guidelines while on study). WCBP must agree to have pregnancy tests every 3 weeks while on study drug (every 14 days for women with irregular cycles) and 4 weeks after the last dose of study drug. Men must also agree to use a condom if their partner is of child bearing potential, even if they have had a successful vasectomy. Exclusion Criteria: Age < 18 years Patients not fit for intensive chemotherapy Complete morphological and cytogenetic remission following intensive combination chemotherapy Absence of HLA compatible donor HIV positive Evidence of graft versus host disease at day+100 post transplant Evidence of relapse of leukaemia (≥5% bone marrow blasts) Concurrent use of other forms of anti-leukaemic therapy Other malignancy with the exception of carcinoma in situ. Significant history of heart disease (unstable angina, myocardial within the past six months, congestive cardiac failure requiring daily treatment) Evidence of active lung disease determined by chest x-ray and absence of chronic lung disease (FEV1<60% predicted, Vital capacity <60%, Tlco<50%)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cohort 1<br>AML Cell Vaccine alone | Biological: RFUSIN2-AML1<br>* AML cell vaccine alone. x4 doses 3 weeks apart<br>|
| Experimental: cohort 2<br>Donor leukocytes alone | Biological: Donor leukocyte infusion (DLI)<br>* 1 dose 1x107/kg<br>* Other names: RFUSIN2-AML1;|
| Experimental: cohort 3<br>AML cell vaccine and Donor Leukocyte Infusion (1x107/kg) | Biological: RFUSIN2-AML1 and donor leukocyte infusion<br>* AML cell vaccine x 4 doses 3 weeks apart Donor leukocyte infusion 1x107/kg x 1 dose<br>* Other names: RFUSIN2-AML1;|
| Experimental: cohort 4<br>AML cell vaccine and Donor Leukocyte Infusion (1x108/kg) | Biological: RFUSIN2-AML1 and donor leukocyte infusion<br>* AML cell vaccine x4 doses 3 weeks apart Donor leukocyte infusion 1x108/kg x1 dose<br>* Other names: RFUSIN2-AML1;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity and safety of the 'AML Cell Vaccine' |  | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| relapse, leukaemia free survival and overall survival |  | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute myeloid leukaemia, Cancer vaccines, Immunotherapy