Condition category
Injury, Occupational Diseases, Poisoning
Date applied
05/11/2008
Date assigned
27/11/2008
Last edited
27/11/2008
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof JHF Falkenburg

ORCID ID

Contact details

Department of Haematology
CR-2 Albinusdreef 2
Leiden
2333 ZA
Netherlands
+31 (0)71 526 2271
J.H.F.Falkenburg@lumc.nl

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

LUMC2007-02

Study information

Scientific title

Vaccination with human minor H antigen (HA-1) peptide in patients showing minimal residual disease or mixed chimerism after allogeneic stem cell transplantation and donor lymphocyte infusion

Acronym

Study hypothesis

After allogeneic human leukocyte antigen (HLA)-matched stem cell transplantation (SCT), minor histocompatibility antigens (mHags) are the most likely targets for graft-versus-leukaemia (GvL) associated immune reactivity. Among these mHags, human minor H antigen (HA-1) is expressed by both normal haematopoietic cells and their malignant counterparts. HA-1 specific T-cells have been shown to be capable of eliminating HA-1 positive malignant (precursor) cells in HLA-A2 positive HA-1 positive patients after stem cell transplantation and donor lymphocyte infusion (DLI) administration from a HA-1 negative donor. However, after DLI not all patients develop a HA-1 specific T-cell response and a durable GvL effect in this setting.

We hypothesise that vaccination with administration of HA-1 peptide vaccine in HLA-A2 and HA-1 positive patients who had undergone HLA-matched allogeneic stem cell transplantation followed by DLI from a HLA-A2 positive, HA-1 negative, donor showing persistent disease or mixed chimerism eight weeks after DLI can induce an immunological response without severe graft-versus-host disease (GVHD).

Ethics approval

Central Committee on Research involving Human Subjects (CCMO) gave approval on the 17th March 2008.

Study design

Single arm open label intervention phase I/II study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Mixed chimerism after allogeneic stem cell transplantation

Intervention

Week 0: The study starts when DLI is given in an eligible patient
Week 8: Bone marrow investigation for chimerism and/or disease evaluation. GVHD evaluation and measurement of HA-1 specific T cells. If no HA-1 specific response:
Week 10: First subcutaneous vaccination with HA-1 peptide vaccine and as a control subcutaneous vaccination with Keyhole Limpet Hemocyanin (KLH)
Week 13: Second subcutaneous vaccination with HA-1 peptide vaccine
Week 16: Third subcutaneous vaccination with HA-1 peptide vaccine

Immunological and clinical effects will be evaluated after the first 12 patients treated using the 20mer vaccine. If six or more patients showed an immunological response, the vaccination program using the 20mer vaccine will be continued, aiming for a total number of 24 patients. If less than 6 patients showed an immunologic response, 12 additional patients will be entered and treated using the 20mer + 9mer vaccine If less than 6 patients showed an immunological response to the 20mer + 9mer vaccine, the vaccination strategy using current peptides will be considered inadequate.

Information on vaccines:

20mer vaccine (300 µg peptide):
The subcutaneous 20mer HA-1 vaccine consists of a single peptide representing the amino-acid sequence 133-152 (LKECVLHDDLLEARRPRAHE) of the HA-1 protein encoded by the gene KIAA0223. The peptide is produced in the Interdivisional GMP-Facility of the LUMC (IGFL), Department of Clinical Pharmacy and Toxicology. Montanide ISA 51 is used as an adjuvant.

KLH:
Immucothel (Biosyn Arzneimittel GmbH) 1 mg is used to test the capacity for generating an immune response in the patient).

20mer and 9 mer combination vaccine (300 µg 20-mer peptide and 250 µg 9-mer peptide):
This investigational medical product (IMP) consists of a peptide that comprises LKECVLHDDLLEARRPRAHE, representing the amino-acid sequence 133-152 of the HA-1 protein encoded by the gene KIAA0223, in combination with a peptide that comprises VLHDDLLEA, representing the amino-acid sequence 137-145 of the HA-1 protein encoded by the gene KIAA0223. The peptides are produced in the Interdivisional GMP-Facility of the LUMC (IGFL), Department of Clinical Pharmacy and Toxicology. Montanide ISA 51 is used as an adjuvant.

Total follow-up is 26 weeks after week 0 (so 16 weeks after vaccination).

Intervention type

Drug

Phase

Phase I/II

Drug names

Human minor H antigen (HA-1) peptide

Primary outcome measures

1. Toxicity (phase 1), monitored every two weeks until end of study
2. Appearance of HA-1 specific CD8+ lymphocytes, monitored at weeks 6 and 8 and from 10 - 26 weeks after DLI

Secondary outcome measures

1. Bone marrow chimerism, monitored at weeks 8, 12, 15, 19 and 26
2. Disease activity, monitored at weeks 8, 12, 15, 19 and 26

Overall trial start date

01/12/2008

Overall trial end date

01/12/2012

Reason abandoned

Eligibility

Participant inclusion criteria

1. Patients with acute myeloid leukaemia (AML), myelodysplasia (MDS), acute lymphoblastic leukaemia (ALL), chronic myeloid leukaemia (CML) in accelerated phase or blastic transformation before transplantation, chronic lymphocytic leukaemia (CLL), multiple myeloma (MM) or aggressive lymphoma, who underwent allo-SCT (both myeloablative and non-myeloablative) followed by DLI for persistent mixed chimerism or smoldering disease
2. Patient and donor HLA-A2 positive, patient HA-1 positive, donor HA-1 negative
3. World Health Organization (WHO) performance status of 0, 1 or 2
4. Female patients of childbearing potential must be neither pregnant nor breastfeeding and must agree to use effective contraception (birth control pills, condoms, approved implant, or intra-uterine device [IUD]) during the course of this trial and for at least three months after the last injection
5. Mixed chimerism or persisting disease 8 weeks after DLI
6. Male and female, aged 18 years and older

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

24

Participant exclusion criteria

1. Life expectation of less than 3 months
2. Psychological disturbances
3. Severely limited life expectation due to diseases other than the malignancy
4. Human immunodeficiency virus (HIV) positivity
5. Persistent treatment with high-dose corticosteroids (greater than 20 mg prednisone a day), chemotherapy or other immunosuppressive drugs
6. Rapidly progressive disease
7. GVHD grade 3 or 4
8. HA-1 specific immune response (defined by greater than 0.2% of total CD8+ cells in first six patients and defined by greater than 1.0% of total CD8+ cells in patients 4 - 24 if no toxicity greater than grade II in first three patients). No important increase in percentage HA-1 specific CD8+ cells between 6 and 8 weeks after DLI (defined as a doubling of this percentage resulting in a percentage of greater than 0.2%).

Recruitment start date

01/12/2008

Recruitment end date

01/12/2012

Locations

Countries of recruitment

Netherlands

Trial participating centre

Department of Haematology
Leiden
2333 ZA
Netherlands

Sponsor information

Organisation

Leiden University Medical Centre (LUMC) (Netherlands)

Sponsor details

Albinusdreef 2
Leiden
2333 ZA
Netherlands
+31 (0)71 526 2267
c.j.m.halkes@lumc.nl

Sponsor type

Hospital/treatment centre

Website

http://www.lumc.nl/english/start_english.html

Funders

Funder type

Research organisation

Funder name

Dutch Cancer Society (KWF Kankerbestrijding) (The Netherlands)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes