To Study Lower Dose of Cyclophosphamide After Stem Cell Transplant for Blood Cancers
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorTata Memorial Centre
About this trial
Cyclophosphamide is the name of a medicine given to prevent graft-versus-host-disease (GVHD) after half-matched transplant. This medicine is given on the 3rd and 4th day after stem cell transplant. The standard dose of this medicine is 50 mg per kg of the patient's weight given on the 3rd and the 4th day. However, using this medicine at this dose of 50 mg / kg for 2 days is associated with certain problems such as susceptibility to infections and delay in the recovery of the immune system after stem cell transplant. Therefore, several research groups across the world have tried to reduce the dose of cyclophosphamide that is used. These groups have tried reducing the dose from 50 mg per kg to 25-40 mg per kg. These studies have shown that the reduced dose cyclophosphamide is equally effective in preventing GVHD. However, these studies are carried out on small numbers of patients and further studies are essential to confirm whether reduced dose of cyclophosphamide is equally effective. In this study, we will use cyclophosphamide at a lower dose (25 mg/kg x 2 days) and see if the lower dose results in equal efficacy but lesser toxicities This is a single-arm study. All participants will receive the same treatment; there is no comparison group.
Participants will:
Adults (age ≥18) undergoing haploidentical stem cell transplant for blood cancers Receive low-dose cyclophosphamide (25 mg/kg/day) on Day 3 and Day 4 after transplant Also receive standard GVHD preventive medicines (calcineurin inhibitor and mycophenolate) Undergo regular blood tests, immune system monitoring, and GVHD assessments Have immune cell and cytokine profiles analyzed through blood samples
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patients age ≥ 18 years
ECOG performance score of 0 or 1
Disqualifiers
Presence of an active uncontrolled infection defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs, or radiographic findings attributable to infection.
Any medical or psychiatric illness which precludes the participant from giving informed consent.
Serious cardiac dysfunction: Left ventricular ejection fraction < 45%; no uncontrolled arrhythmias or symptomatic cardiac disease.
Serious pulmonary organ dysfunction: Symptomatic pulmonary disease; forced expiratory volume in one second (FEV1), forced vital capacity (FVC), diffusion capacity of the lung for carbon monoxide (DLCO) =< 50% of predicted (corrected for haemoglobin).
Trial design
Design model
Single group
Treatments tested in this trial
Cyclophosphamide
DrugPost-transplant Immunosuppression: ● GvHD prophylaxis regimen will consist of two doses of cyclophosphamide on D+3 and D+4 at 25mg/kg/day (that is half of the usual standard dose) with calcineurin inhibitor and mycophenolate mofetil / mycophenolate sodium. Mesna will be given with cyclophosphamide (this is standard of care). The use of calcineurin inhibitors and mycophenolate mofetil / mycophenolate sodium will be as per standard practice. Administration of study treatments * Hydration and MESNA * Adequate intravenous hydration with normal saline will be started at least 4 hours prior to cyclophosphamide, and will be continued till 24 hours post completion of 2nd dose of cyclophosphamide as per standard institutional practice. * Mesna will be administered as a continuous infusion starting from Day+3 till 24 hours after the second dose of PTCy. * Cyclophosphamide * Cyclophosphamide would be administered on D+3 and D+4 \[first dose starting between 60 - 72 hrs after stem cell infusion\]
Treatment groups
20 Participants
are divided into 1 treatment groupGroup A: Low dose cyclosphosphamideExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Severe (Grade 3-4) aGvHD
To evaluate the cumulative incidence of severe (Grade 3-4) aGvHD
Time frame
at day 100 Post TransplantSecondary outcomes
1
Cumulative incidence of clinically significant (Grade 2-4) acute graft-versus-host disease (aGvHD)
To evaluate the cumulative incidence of clinically significant (Grade 2-4) acute GvHD following transplantation.
Time frame
Day 100 and Day 180 post-transplant2
Cumulative incidence of severe (Grade 3-4) acute graft-versus-host disease (aGvHD)
To evaluate the cumulative incidence of severe (Grade 3-4) acute GvHD following transplantation.
Time frame
Day 180 post-transplant3
Graft-versus-host disease and relapse-free survival (GRFS)
To evaluate graft-versus-host disease and relapse-free survival (GRFS). GRFS events include grade III or IV acute GvHD, extensive chronic GvHD, disease relapse, or death.
Time frame
1 year post-transplant4
Incidence of chronic graft-versus-host disease (cGvHD
To evaluate the cumulative incidence of chronic GvHD following transplantation.
Time frame
1 year post-transplantSponsors and contacts
Click on the lead sponsor to view all of their trials.
Tata Memorial Centre
Lead sponsor
Indian Council of Medical Research
Collaborator
Source ClinicalTrials.gov