RFUSIN2-AML1: Lentivirus Transduced Acute Myeloid Leukaemia Blasts Expressing B7.1 (CD80) and IL-2

Sponsor

King's College Hospital NHS Trust (Other)

Overall Status

Unknown status

CT.gov ID

NCT00718250

Collaborator

Department of Health (Other), Leukemia Research Fund (Other), Elimination of Leukaemia Fund (Other)

Enrollment

Location

Arms

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Leukemia, Myeloid, Acute	Biological: RFUSIN2-AML1 Biological: Donor leukocyte infusion (DLI) Biological: RFUSIN2-AML1 and donor leukocyte infusion Biological: RFUSIN2-AML1 and donor leukocyte infusion	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

Non-Randomized

Intervention Model:

Factorial Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

May 1, 2008

Anticipated Primary Completion Date :

May 1, 2011

Anticipated Study Completion Date :

Feb 1, 2012

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Toxicity and safety of the 'AML Cell Vaccine' [one year]

Secondary Outcome Measures

relapse, leukaemia free survival and overall survival [one year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

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%)