| CTRI Number |
CTRI/2024/11/077468 [Registered on: 28/11/2024] Trial Registered Prospectively |
| Last Modified On: |
26/11/2024 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Single Arm Study |
|
Public Title of Study
|
To study Lower Dose of Cyclophosphamide after Stem Cell Transplant for Blood Cancers |
|
Scientific Title of Study
|
Phase II trial of Reduced dose Post transplant Cyclophosphamide after Haploidentical Hematopoietic Stem Cell Transplant in Hematological malignancies |
| Trial Acronym |
NIL |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Sachin Punatar |
| Designation |
Professor and Medical Oncologist |
| Affiliation |
Advanced Centre for Treatment Research and Education in Cancer Tata Memorial Centre |
| Address |
Department of Medical oncology Adult hematolymphoid and Bone marrow transplant unit OPD room no 103 and 307 Shanti sadan ACTREC Tata Memorial Centre sector 22 Kharghar Navi Mumbai
Raigarh
MAHARASHTRA
410210
India |
| Phone |
09833445041 |
| Fax |
|
| Email |
drsachin_punatar@yahoo.in |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Sachin Punatar |
| Designation |
Professor and Medical Oncologist |
| Affiliation |
Advanced Centre for Treatment Research and Education in Cancer Tata Memorial Centre |
| Address |
Department of Medical oncology Adult hematolymphoid and Bone marrow transplant unit OPD room no 103 and 307 Shanti sadan ACTREC Tata Memorial Centre sector 22 Kharghar Navi Mumbai
MAHARASHTRA
410210
India |
| Phone |
09833445041 |
| Fax |
|
| Email |
drsachin_punatar@yahoo.in |
|
Details of Contact Person
Public Query
|
| Name |
Dr Sachin Punatar |
| Designation |
Professor and Medical Oncologist |
| Affiliation |
Advanced Centre for Treatment Research and Education in Cancer Tata Memorial Centre |
| Address |
Department of Medical oncology Adult hematolymphoid and Bone marrow transplant unit OPD room no 103 and 307 Shanti sadan ACTREC Tata Memorial Centre sector 22 Kharghar Navi Mumbai
MAHARASHTRA
410210
India |
| Phone |
09833445041 |
| Fax |
|
| Email |
drsachin_punatar@yahoo.in |
|
|
Source of Monetary or Material Support
|
| Extramural Indian Council of Medical Research address V. Ramalingaswami Bhawan, P.O. Box No. 4911Ansari Nagar New Delhi 110029 India |
|
|
Primary Sponsor
|
| Name |
ACTREC Tata Memorial Centre |
| Address |
Plot No. 1& 2 Sector 22 Utsav Chowk CISF Road Owe Camp Kharghar Navi Mumbai 410210 Maharashtra India |
| Type of Sponsor |
Research institution and hospital |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Sachin Punatar |
Advanced Centre for Treatment Research and Education in Cancer, Tata Memorial Centre |
Department of Medical oncology Adult hematolymphoid and Bone marrow transplant unit OPD room no 103 and 307 Shanti sadan ACTREC Tata Memorial Centre Kharghar Navi Mumbai
Raigarh
MAHARASHTRA |
09833445041
drsachin_punatar@yahoo.in |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Tata Memorial Centre Advanced Centre for Treatment, Research and Education in Cancer Institutional Ethics Committee (TMC-IEC III) |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: C969||Malignant neoplasm of lymphoid, hematopoietic and related tissue, unspecified, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Cyclophosphamide. |
Post-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
Study treatment: Cyclophosphamide.
Dosage schedule: Day+3 and Day+4 of transplant.
Route/Mode of administration: Intravenous infusion over 2 hrs with Mesna.
Details
-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 would be administered on D+3 and D+4 [first dose starting between 60 - 72 hrs after stem cell infusion] at a dose of 25 mg/kg/day intravenously as an intravenous infusion over 2 hrs. The timing of cyclophosphamide and the infusion time of 2 hours are standard of care. The actual administered dose can be rounded off to the nearest 100 mg (Eg if the dose is 1760 mg, the actual administered dose can be 1800 mg)
|
| Comparator Agent |
Nil |
Nil |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
80.00 Year(s) |
| Gender |
Both |
| Details |
1.ECOG performance score of 0 or 1
|
|
| ExclusionCriteria |
| Details |
1.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.
2.Any medical or psychiatric illness which precludes the participant from giving informed consent.
3.Organ function criteria: Serious organ dysfunctions:
a.Serious cardiac dysfunction: Left ventricular ejection fraction less than 45 percent; no uncontrolled arrhythmias or symptomatic cardiac disease.
b.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) equal to or less than 50 percent of predicted (corrected for haemoglobin).
c.Serious renal dysfunction: Measured serum creatinine clearance equal to or less 60 mL per min.
d.Serious Hepatic dysfunction: Total serum bilirubin more than twice upper normal limit or Alanine aminotransferase (ALT) or aspartate aminotransferase |
|
|
Method of Generating Random Sequence
|
Not Applicable |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| To evaluate the cumulative incidence of severe (Grade 3-4) aGvHD |
at day 100 Post Transplant |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
1.To evaluate the cumulative incidence of clinically significant (Grade2-4) aGvHD at Day 100 and Day 180.
2.To evaluate the cumulative incidence of severe (Grade 3-4) aGvHD at Day 180.
3.To evaluate the GvHD and relapse free survival (GRFS) rate at 1 year post transplant (GRFS events will include grade III or IV acute GVHD, or extensive chronic GVHD or disease relapse).
4.To study the incidence of chronic GvHD at 1 year post transplant.
5.To study the engraftment kinetics
6.Safety Regimen Related Toxicity [Time Frame 100 Days Post Transplant]
7.To study the transplant related mortality (TRM) at 1 year post transplant.
8.To study the overall survival (OS) at 1 year post transplant. |
Day 100, Day 180 and 1 year post transplant |
|
|
Target Sample Size
|
Total Sample Size="20"
Sample Size from India="20"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 2 |
|
Date of First Enrollment (India)
|
10/12/2024 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="4"
Months="0"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
Brief summary 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.
Study synopsis
Background: Allogeneic Hematopoietic stem cell
transplant (HSCT) is often the only curative treatment option for patients with
end stage hematological malignancies. Haploidentical HSCT is increasingly being
adopted worldwide due to ease of access to donors. Post transplant
cyclophosphamide (PTCy) has revolutionized the way the world does T cell
replete haploidentical transplant. However, the success of PTCy comes at the
cost of delayed engraftment and increased organ toxicities. Reduced dose of
PTCy may be equally effective in GvHD prevention and translate into better
engraftment kinetics and immune reconstitution.
Novelty: The proposed study is a prospective
phase 2 trial of reduced dose PTCy as GvHD prophylaxis in haplo HSCT. By
demonstration of equal GvHD prevention efficacy of reduced dose PTCy this study
would provide the base for phase 3 randomised trial and provide practice
changing answers.
Objectives: To evaluate the GvHD prophylactic
effect of reduced dose PTCy in combination with Calcineurin inhibitors and MMF
for haploidentical HSCT.
Methods: Following patient enrolment and
drug administration the GvHD grade, engraftment kinetics, cytokine profile and
immune reconstitution will be evaluated.
Expected Outcome: Combination of reduced dose PTCy
with calcineurin inhibitors and MMF may be equally effective in reducing severe
aGvHD as standard dose PTCy.
|