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Antibody Mediated RejectionPhase 2NCT01630538

Cyclophosphamide Therapy for Refractory Antibody-Mediated Rejection (AMR) in Kidney Transplants

A Phase 2 study testing Cyclophosphamide in people with Antibody Mediated Rejection, run by University of Manitoba at 1 site in Canada.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The study hypothesis is that short-term low dose cyclophosphamide therapy will be effective in resolving inflammation in patients with late phase antibody-mediated rejection refractory to current standard of care treatment. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Antibody Mediated Rejection
What is being tested?
Cyclophosphamide
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4 participants
Where
1 siteCanada
Study dates
Jun 2013to 18 Jan 2018
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with a living or deceased donor kidney transplant
  • Failed current standard of care for late antibody-mediated rejection
  • Persistent de novo donor specific antibody and a concurrent biopsy with histologic evidence of acute antibody-mediated inflammation
  • Adults with reproductive potential must agree to use approved methods of birth control while in the study

Who cannot join

  • Leukopenia (WBC) < 3.0 x 109/L
  • Creatinine Clearance less than or equal to 25 ml/min/1.73m2
  • HCV or HBV positive
  • BKV or CMV viremia assessed by PCR
  • Any active infection
  • Use of other investigational drugs within 4 weeks of study
Show all 12Show fewer
  • Pregnancy/breast feeding/unwilling or unable to take birth control
  • Active malignancy
  • de novo DSA occurring equal to or greater than15 years after kidney transplant
  • Screening biopsy with equal to or greater than cg2 on Banff criteria
  • Cumulative/lifetime dose of cyclophosphamide, including anticipated total study dose (calculated according to Creatinine Clearance and mg/kg/day) equal to or greater than 36 g.
  • Any condition that, in the opinion of the investigator, would pose risk to the subject's safe participation in the study

Trial locations and contacts

1 site in 1 country.

Canada1 site

  • Transplant Manitoba Adult Kidney Transplant Program, Health Sciences Centre

    Winnipeg, Manitoba

Other trials in Canada

About this study

Official title: Phase II Pilot Study of Cyclophosphamide Therapy for Refractory Antibody-Mediated Rejection in Kidney Transplantation

The study hypothesis is that short-term low dose cyclophosphamide therapy will be effective in resolving inflammation in patients with late phase antibody-mediated rejection refractory to current standard of care treatment.

Read the detailed description

There is no consensus on the optimal treatment of de novo donor specific antibody-mediated rejection. Optimizing baseline immunosuppression (calcineurin inhibitor (CNI), anti-proliferative agent, and anti-inflammatory) is considered foundational but is insufficient. Pulse steroids are routinely used. A number of immunosuppressive approaches have been tried in uncontrolled trials. The strongest evidence, at least for early antibody-mediated rejection (< 6 months from transplant), exists for plasmapheresis, with or without low dose IVIg, or high dose IVIg alone. However, as noted in a recent FDA workshop, "while the literature suggests that [these agents] have evidence of efficacy for the management of acute antibody-mediated rejection, and could be considered as standard of care, treatment regimes have not been standardized or optimized." Moreover the evidence supporting efficacy of this approach in late, as opposed to early antibody-mediated rejection is distinctly lacking.

Being tested
Cyclophosphamide
Keywords
Transplantation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CyclophosphamideDrug

    Also called Procytox

    Cyclophosphamide 1.5 mg/kg orally daily for 180 days adjusted for renal function

Study groups in NCT01630538
Study groupRoleWhat they receive
CyclophosphamideExperimentalCyclophosphamide 1.5 mg/kg orally daily for 180 days (26 weeks) adjusted for renal function.
Receives: Drug: Cyclophosphamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Microvascular inflammation

    Histologic resolution of acute antibody-mediated inflammation in a 6 month post-treatment biopsy (Banff histology scores: g, v, ptc, C4d +ve)

    Measured: month 6

Secondary outcomes (6)

  1. titre of donor specific antibody (DSA)

    Change in the level of de novo DSA between enrolment and at 6 and 12 months post-enrollment

    Measured: 6 and 12 months

  2. antibody-mediated tissue injury

    Change in antibody-mediated tissue injury between the enrollment and post-treatment kidney transplant biopsy samples

    Measured: month 6

  3. Urine Albumin/Creatinine ratios

    Change in urine albumin/creatinine ratio between enrolment and 6 and 12 month post-enrolment samples

    Measured: month 6 and 12

  4. Creatinine Clearance and estimated GFR

    Evaluation of Creatinine Clearance, and estimated GFR using the Chronic Kidney Disease Epidemiology (CKR-EPI) equation

    Measured: month 6 and 12

  5. Graft Survival

    Measured: month 6 and 12

  6. Patient Survival

    Measured: month 6 and 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jun 2012 (estimated)
  2. Study startJun 2013
  3. Primary completion18 Jan 2018
  4. Study completion18 Jan 2018

Why it stopped: After March 2015, unable to enroll due to patients meeting exclusion criteria.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01630538
Sponsor's protocol ID
TMCT-01
Status last verified
Apr 2018
First submitted
25 Jun 2012
Last updated
19 Apr 2018
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Undecided

Publications

  • Wiebe C, Gibson IW, Blydt-Hansen TD, Karpinski M, Ho J, Storsley LJ, Goldberg A, Birk PE, Rush DN, Nickerson PW. Evolution and clinical pathologic correlations of de novo donor-specific HLA antibody post kidney transplant. Am J Transplant. 2012 May;12(5):1157-67. doi: 10.1111/j.1600-6143.2012.04013.x. Epub 2012 Mar 19.

    PubMed 22429309

  • Archdeacon P, Chan M, Neuland C, Velidedeoglu E, Meyer J, Tracy L, Cavaille-Coll M, Bala S, Hernandez A, Albrecht R. Summary of FDA antibody-mediated rejection workshop. Am J Transplant. 2011 May;11(5):896-906. doi: 10.1111/j.1600-6143.2011.03525.x.

    PubMed 21521465

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cyclophosphamide in people with Antibody Mediated Rejection, run by University of Manitoba at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 19 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: After March 2015, unable to enroll due to patients meeting exclusion criteria.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Microvascular inflammation (time frame: month 6). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01630538, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2018.

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