AzTrials
AzTrials

Leukemia, Acute LymphoblasticPhase 1/2NCT02799147

GVHD Prophylaxis With Post-transplantation Bendamustine in Refractory Leukemia

A Phase 1/2 study testing Allogeneic stem cell transplantation, Fludarabine monophosphate and Busulfan in people with Leukemia, Acute Lymphoblastic and Acute Myeloid Leukemia, run by St. Petersburg State Pavlov Medical University at 1 site in Russia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Several groups have demonstrated very low incidence of acute and chronic graft-versus-host disease (GVHD) with post-transplantation cyclophosphamide (PTCy) in haploidentical, unrelated and related allogeneic stem cell transplantation (SCT). Read more about this study

Who is it for?
Ages 18 to 60 years
What is being tested?
Allogeneic stem cell transplantation, Fludarabine monophosphate and Busulfan
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
1 siteRussia
Study dates
Jun 2016to Nov 2020
Phase
Phase 1/2
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 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Diagnosis: Acute Myeloblastic Leukemia Acute Lymphoblastic Leukemia Mixed-Lineage Acute Leukemias
  • Disease, refractory to at list one course of induction chemotherapy or immunotherapy
  • More than 5% clonal blasts in the bone marrow or peripheral blood at the time of inclusion
  • Signed informed consent
  • Matched related, 8-10/10 HLA-matched unrelated or haploidentical donor available. The HLA typing is performed by the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA-DQB1.
  • No second tumors
  • No severe concurrent illness
  • No previous autologous or allogeneic stem cell transplantations

Who cannot join

  • Karnofsky index <70%
  • Moderate or severe cardiac dysfunction, left ventricular ejection fraction <50%
  • Moderate or severe decrease in pulmonary function, FEV1 <70% or DLCO<70% of predicted
  • Respiratory distress >grade I
  • Severe organ dysfunction: AST or ALT >5 upper normal limits, bilirubin >1.5 upper normal limits, creatinine >1.5 upper normal limits
  • Creatinine clearance < 60 mL/min
Show all 10Show fewer
  • Uncontrolled bacterial or fungal infection at the time of enrollment, defined by CRP level >70 mg/L or positive procalcitonin in patient with adequate empirical antibacterial and antifungal therapy.
  • Requirement for vasopressor support at the time of enrollment
  • Pregnancy
  • Somatic or psychiatric disorder making the patient unable to sign informed consent

Trial locations and contacts

1 site in 1 country.

Russia1 site

  • First Pavlov State Medical University of St. Petersburg

    Saint Petersburg, 197089

Other trials in Russia

About this study

Official title: Dose-escalation Study of Graft-versus-host Disease Prophylaxis With High-dose Post-transplantation Bendamustine in Patients With Refractory Acute Leukemia

Several groups have demonstrated very low incidence of acute and chronic graft-versus-host disease (GVHD) with post-transplantation cyclophosphamide (PTCy) in haploidentical, unrelated and related allogeneic stem cell transplantation (SCT). Nonetheless for majority of the grafts, except for 10/10 HLA-matched bone marrow, with this type of prophylaxis require concomitant administration of calcineurin inhibitors±MMF, which delays immune reconstitution and development of graft-versus-leukemia (GVL) effect. So, despite reduction of transplant-related mortality, use of PTCy doesn't lead to the reduction of relapse incidence. This is particularly important for relapsed or refractory acute leukemia patients, where, despite all efforts to intensify conditioning regimens, relapses after SCT occur in more than 50% of patients, and long-term survival rarely exceeds 10-20%. In preclinical model of haploidentical SCT the substitution of post-transplantation cyclophosphamide with bendamustine, led to comparable GVHD control, but significantly augmented GVL effect. To test this hypothesis and improve the outcome of allogeneic SCT in refractory acute leukemia patients we initiated a pilot trial with high-dose post-transplantation bendamustine for GVHD prophylaxis. The selection of doses is based on the previous dose-escalation studies. Additional immunosuppression could be added for mismatched grafts.

Being tested
Allogeneic stem cell transplantation, Fludarabine monophosphate, Busulfan, Bendamustine
Keywords
Allogeneic Transplantation, Hematopoietic Stem Cell Transplantation, Leukemia, Acute Lymphoblastic, Acute Myeloid Leukemia, Mixed-Lineage Acute Leukemias, Immune System Diseases, Immunosuppressive Agents, Myeloablative Agonists, Busulfan, Fludarabine, Antineoplastic Agents, Alkylating, Bendamustine Hydrochloride
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Leukemia, Biphenotypic, Acute, Immune System Diseases

What participants receive

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

  • Allogeneic stem cell transplantationProcedure or surgery

    Also called HSCT

  • Fludarabine monophosphateDrug

  • BusulfanDrug

  • BendamustineDrug

Study groups in NCT02799147
Study groupRoleWhat they receive
280 mg/m2 bendamustineExperimental10 patients Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days Days -6 through -3: Busulfan 1 mg/kg po qid №14 Day 0: Infusion of unmanipulated graft Day +3 and +4: Bendamustine 140 mg/m2/day iv.
Receives: Procedure: Allogeneic stem cell transplantation; Drug: Fludarabine monophosphate; Drug: Busulfan; Drug: Bendamustine
200 mg/m2 bendamustineExperimental10 patients Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days Days -6 through -3: Busulfan 1 mg/kg po qid №14 Day 0: Infusion of unmanipulated graft Day +3 and +4: Bendamustine 100 mg/m2/day iv
Receives: Procedure: Allogeneic stem cell transplantation; Drug: Fludarabine monophosphate; Drug: Busulfan; Drug: Bendamustine
140 mg/m2 bendamustineExperimental10 patients Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days Days -6 through -3: Busulfan 1 mg/kg po qid №14 Day 0: Infusion of unmanipulated graft Day +3, +4: Bendamustine 70 mg/m2/day iv.
Receives: Procedure: Allogeneic stem cell transplantation; Drug: Fludarabine monophosphate; Drug: Busulfan; Drug: Bendamustine

What is being measured

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

  1. Engraftment rate

    Engraftment is defined as the first of 3 consecutive days with an ANC>500 per μl and WBC>1000 per μl. Platelet engraftment is not mandatory for the endpoint.

    Measured: 60 days

Secondary outcomes (8)

  1. Relapse rate analysis

    Measured: 365 days

  2. Non-relapse mortality analysis

    Measured: 365 days

  3. Incidence of acute GVHD, grades II-IV

    Measured: 180 days

  4. Incidence of chronic GVHD, moderate and severe (NIH criteria)

    Measured: 365 days

  5. Overall survival analysis

    Measured: 365 days

  6. Event-free survival analysis

    Measured: 365 days

  7. Toxicity (NCI CTCAE 4.03)

    Toxicity parameters based on NCI CTCAE 4.03 grades: hepatotoxicity (liver function tests), nephrotoxicity (creatinine), neurotoxicity (attending physician assessment), mucositis (attending physician assessment), hemorrhagic cystitis (attending physician assessment), cardiotoxicity (ECG, echocardiography). Additional toxicity parameters: incidence and severity of veno-occlusive disease, incidence of transplant-associated microangiopathy

    Measured: 100 days

  8. Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence

    Measured: 100 days

Timeline

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

  1. First posted14 Jun 2016 (estimated)
  2. Study startJun 2016
  3. Primary completionNov 2020
  4. Study completionNov 2020

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
27 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02799147
Sponsor's protocol ID
05/16-n
Status last verified
Nov 2020
First submitted
9 Jun 2016
Last updated
23 Nov 2020
Results posted
No
Data monitoring committee
No
Individual data sharing
Undecided: Consultations are ongoing about how IPD initiative fits the local law "About personal data 152-fz".

Publications

  • Stokes J, Hoffman EA, Zeng Y, Larmonier N, Katsanis E. Post-transplant bendamustine reduces GvHD while preserving GvL in experimental haploidentical bone marrow transplantation. Br J Haematol. 2016 Jul;174(1):102-16. doi: 10.1111/bjh.14034. Epub 2016 Mar 31.

    PubMed 27030315

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Allogeneic stem cell transplantation, Fludarabine monophosphate and Busulfan in people with Leukemia, Acute Lymphoblastic and Acute Myeloid Leukemia, run by St. Petersburg State Pavlov Medical University at 1 site in Russia.

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 8 inclusion and 10 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: finished, as of the sponsor's last update on 23 Nov 2020. 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 Russia. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Engraftment rate (time frame: 60 days). 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 NCT02799147, which also lists 1 linked publication.

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 23 Nov 2020.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in