Hematopoietic Stem Cell Transplant (HSCT)Phase 1/2NCT07724873
Study to Evaluate the Safety and Effectiveness of Withaferin A as a Treatment to Prevent GvHD in Transplant Patients
A Phase 1/2 study testing SWA (standardized root extract of Withania somnifera) in people with Hematopoietic Stem Cell Transplant (HSCT) and GVHD - Graft-Versus-Host Disease, run by Tata Memorial Centre at 2 sites in India.
Trial summary
What is acute Graft versus host disease (aGvHD)? GvHD is a complication that can occur after an allogeneic stem cell transplant resulting in damage to some organs. The death rate of GvHD patients is 15-40%. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hematopoietic Stem Cell Transplant (HSCT), GVHD - Graft-Versus-Host Disease, Hematological Malignancy
- What is being tested?
- SWA (standardized root extract of Withania somnifera)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 2 sitesIndia
- Study dates
- 28 Jan 2025to 3 Dec 2029
- Phase
- Phase 1/2
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
- ECOG performance score of 0 or 1
- Adequate liver function (Total serum bilirubin < twice upper normal limit or Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 3-fold higher than laboratory upper normal limits)
- Adequate renal function (creatinine clearance > 50 ml/min)
- Adequate cardiac function (LVEF>40%)
- Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration.
- Signed, written informed consent
Who cannot join
- Known hypersensitivity or contraindications against Withaferin-A.
- 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
- Pregnancy, lactation, or inadequate contraception.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Dr Akanksha Chichra, FNB, DNB Pediatric oncology contact
Dr Sachin Punatar, MBBS MD DM Medical Oncology contact
India2 sites, 2 recruiting
- Recruiting
Advanced Centre for Treatment, Research and Education in Cancer
Navi Mumbai, Maharashtra, 410210
Akanksha Chichra, FNB DNB Pediatric oncology, 09004920555, akanksha7@hotmail.com
sachin Punatar, MBBS DM MD Medical Oncology, 09833445041, drsachin_punatar@yahoo.in
- Recruiting
Advanced Centre for Treatment, Research and Education in Cancer
Navi Mumbai, Maharashtra, 410210
Akanksha Chichra, FNB DNB Pediatric oncology, 09004920555, akanksha7@hotmail.com
sachin Punatar, MBBS DM MD Medical Oncology, 09833445041, drsachin_punatar@yahoo.in
About this study
Official title: A Phase I/II Trial to Assess Safety and Activity of Standardized Withaferin A as GvHD Prophylaxis in Patients Undergoing Matched Related Donor Hematopoietic Stem Cell Transplant
What is acute Graft versus host disease (aGvHD)? GvHD is a complication that can occur after an allogeneic stem cell transplant resulting in damage to some organs. The death rate of GvHD patients is 15-40%. In GvHD, the donated peripheral blood stem cells or bone marrow view the recipient's body as foreign, and the donated cells/bone marrow harm the body. aGvHD usually develops in skin, liver or gastrointestinal tract, and symptoms might appear within few weeks after transplant. Symptoms of acute GvHD are observed as skin rash or reddened areas on the skin, yellow discoloration of the skin and/or eyes, and abnormal blood test results, nausea, vomiting, diarrhea, or abdominal cramping.
What is the current prevention used for GvHD? To prevent development of GvHD many standard drugs like cyclosporine (CSA), tacrolimus (TAC), methotrexate (MTX), mycophenolate mofetil (MMF), rapamycin and cyclophosphamide are given.
Read more
What is standardized Withaferin-A (SWA)? Withaferin-A (WA) is the main active component of Withania somnifera (Ashwagandha). It has been shown in many studies to have properties of healing and immune-modulation (improving the immune system). Studies have been done in our Clinical Pharmacology Laboratory that have shown a significant beneficial effect of this drug, when added to the standard drugs used for prophylaxis of GvHD, on reducing the risk of acute GvHD. The drug has also been tested and proven to be very safe in humans.
What is the rationale of this trial? As has been described earlier, GvHD is a difficult complication of allogeneic stem cell transplant which can lead to increased hospital stay and deaths post-transplant. The standard drugs for prevention of GvHD are cyclosporine (CSA), tacrolimus (TAC), methotrexate (MTX), mycophenolate mofetil (MMF), rapamycin and cyclophosphamide. These drugs also have some side effects during the course of transplant. This points out the need for new preventive drugs that are safe and effective.
SWA is an oral formulation of WA which seems to be beneficial in the early studies done in the Clinical Pharmacology Laboratory, ACTREC. SWA has also been found to be safe at very high doses.
SWA will be given along with the standard drugs given to prevent GvHD. Despite of consuming these drugs, about 40 - 60% patients still develop GvHD. The investigators aim to add SWA to these standard drugs during transplant to reduce significant aGvHD.
How will SWA be given? Participants who agree to participate in this trial and are found to be eligible will be given SWA as a capsule at a dose of 500 mg/day (2 capsules of 250 mg) to 3000 mg/day (6 capsules of 250 mg) as per the dose level allotted to the Patient. The drug will be given for a total duration 90 days starting from Day +1 of transplant. All other standard treatments which are part of a transplant procedure will be carried out without any change.
Participants will be monitored clinically for any adverse events and followed up as per standard protocols post-transplant.
What additional tests will be carried out? Additional blood sampling to study the levels of the drug WA blood samples will be collected at 0, 1, 2, 4, 8 hours on the day of start of SWA (Day +1) and Day +7. Checking immune cell profile and cytokines (which are markers of - immunity levels) will be done at Day+30, Day +90, Day+180, Day+365 from the start of SWA which is also the part of routine care. Blood sample of 5 ml will also be taken at Day 0, Day +14, Day +30, Day +60 and Day +90 after start of drug to see level of some special protein called JAK2 STAT3 protein.
What are the risks involved in participation? According to available literature and information, SWA is a safe and well tolerated drug. In a phase 1 study, Standardized Withaferin-A was administered to Patients with advanced stage osteosarcoma. The drug was well tolerated by Patient up to a dose of 4800 mg. No severe side effects were observed. Increase in liver enzymes and skin rash were the most common side effects. Other side effects included fatigue, fever, swelling, and diarrhea.
What is the possible impact of this trial? If indeed SWA works and prevents GvHD effectively then this could be a breakthrough in treatment. It would help many Pateints to prevent GvHD post allogeneic stem cell transplant and would be a safe, easily available, inexpensive and oral drug for the same. This possibly could benefit and help future Patients who undergo bone marrow transplant (BMT) to have better chances of survival and reduce their financial burden.
Read the detailed description
Background :Acute graft versus host disease (aGvHD) is one of the most serious complications of allogeneic hematopoietic stem cell transplant (AHSCT) leading to high non relapse mortality (NRM). Withaferin A (WA) is the principal active component of Withania somnifera (Ashwagandha) and is known to have anti-inflammatory and immunomodulatory activity.
WA use in GvHD prophylaxis may be beneficial, with the evidence from preclinical models. We designed this study to evaluate the efficacy and safety of oral WA in addition to the standard GvHD prophylaxis backbone in MRD transplants.
Study design :Prospective, single arm, Phase I/II, non-randomized interventional study.
Study population :Patients ≥ 18 years with any hematological malignancy, planned for MRD (10/10 match on high resolution typing) transplant will be enrolled .
Treatment: SWA will be started from Day +1 to Day +90 in addition to the standard GvHD prophylaxis backbone of calcineurin inhibitor and methotrexate. Following standard dose escalation design, patients will be enrolled at 4 dose levels (500 mg OD, 1000 mg OD, 1500 mg OD and 1500 mg BD). Based on the toxicity, pharmacokinetic data and acute GvHD rates the dose will be fixed for the rest of the patients enrolled in the Phase 2 arm Note: Dose escalation: The dose escalation to the next dose level will be made after completion of Day + 30 of all three patients. The 30 days is the safety evaluation period for the determination of MTD which is standard for phase 1 trials Study assessments:1. Baseline CBC, biochemistry, PFT, 2D ECHO/MUGA, GFR and NCCT thorax will be done pre transplant 2. Till Day +100 - Twice weekly OPD follow up with CBC, biochemistry, CMV PCR, clinical evaluation for aGvHD features and toxicity features, engraftment details and chimerism assessment 3. Post-transplant Day 100-Day 365 - Weekly OPD follow up with CBC, biochemistry, CMV PCR, clinical evaluation for GvHD features and chimerism assessment on D+180, D+360 and then yearly basis.
- Disease status assessment by Bone marrow assessment / PET Scan on Day+90 and then at 1 year.
- Conditions
- Hematopoietic Stem Cell Transplant (HSCT), GVHD - Graft-Versus-Host Disease, Hematological Malignancy
- Being tested
- SWA (standardized root extract of Withania somnifera)
- Keywords
- Standardized Withaferin A, Matched related donor Hematopoietic stem cell transplant
- Medical subject headings
- Graft vs Host Disease, Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SWA (standardized root extract of Withania somnifera)Drug
SWA will be started from Day +1 to Day +90 in addition to the standard GvHD prophylaxis backbone of calcineurin inhibitor and methotrexate. Following standard dose escalation design, patients will be enrolled at 4 dose levels (500 mg OD, 1000 mg OD, 1500 mg OD and 1500 mg BD). Based on the toxicity, pharmacokinetic data and acute GvHD rates the dose will be fixed for the rest of the patients enrolled in the Phase 2 arm Note: Dose escalation: The dose escalation to the next dose level will be made after completion of Day + 30 of all three patients. The 30 days is the safety evaluation period for the determination of MTD which is standard for phase 1 trials
| Study group | Role | What they receive |
|---|---|---|
| SWA (standardized root extract of Withania somnifera) | Experimental | SWA will be started from Day +1 to Day +90 in addition to the standard GvHD prophylaxis backbone of calcineurin inhibitor and methotrexate. Following standard dose escalation design, patients will be enrolled at 4 dose levels (500 mg OD, 1000 mg OD, 1500 mg OD and 1500 mg BD). Receives: Drug: SWA (standardized root extract of Withania somnifera) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of oral SWA
Incidence of treatment-emergent adverse events (TEAEs), including Grade ≥3 adverse events assessed using CTCAE v5.0 and PRO-CTCAE v1.0
Measured: Day 1 to Day 90
Peak plasma concentration (Cmax) of Withaferin A
Maximum observed plasma concentration following oral administration
Measured: During PK sampling (Phase I)
Area Under the Plasma Concentration-Time Curve (AUC)
Area under the plasma concentration-time curve of Withaferin A
Measured: During PK sampling (Phase I)
Recommended Phase II Dose (RP2D)
RP2D determined based on safety, tolerability and PK findings
Measured: By completion of Phase I (Day 90)
Cumulative incidence of clinically significant acute GvHD (Grade 2-4)
Incidence of Grade 2-4 acute GvHD according to standard grading criteria
Measured: Day 100 post-transplant
Secondary outcomes (7)
Cumulative incidence of severe acute GvHD (Grade 3-4)
Incidence of Grade 3-4 acute GvHD
Measured: Day 100 and Day 180
GvHD-free and relapse-free survival (GRFS
Participants alive without Grade III-IV acute GvHD, chronic GvHD requiring systemic therapy, relapse, or death
Measured: 1 year
Incidence of chronic GvHD
Incidence of chronic GvHD according to NIH criteria
Measured: 1 year
Time to neutrophil engraftment
Time to neutrophil engraftment, defined as the first of three consecutive days with an absolute neutrophil count (ANC) >500 cells/mm³ following hematopoietic stem cell transplantation.
Measured: Up to Day 30 post-transplant
Time to platelet engraftment
Time to platelet engraftment, defined as the first day of a platelet count >20,000 cells/mm³ without platelet transfusion during the preceding 7 days.
Measured: Up to Day 100 post-transplant
Non-relapse mortality (NRM)
Death without prior disease relapse
Measured: 1 year
Overall survival (OS)
Time from transplant until death from any cause
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2026
- Study start28 Jan 2025
- Primary completion3 Dec 2029 (estimated)
- Study completion3 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (26)Papers the sponsor has linked to this study.
- Other trials for Hematopoietic Stem Cell Transplant (HSCT)Studies of the same condition, open and under way.
- More trials run by Tata Memorial CentreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Prospective, single arm, Phase I/II interventional study
- Masking
- None (open label)
- Enrolment
- 54 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tata Memorial Centre
- Sponsor type
- University, hospital or other
- Collaborators
- Indian Council of Medical Research
- Responsible party
- Principal investigator, Akanksha Chichra, Tata Memorial Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07724873
- Sponsor's protocol ID
- 901067
- Status last verified
- Jul 2026
- First submitted
- 11 Jul 2026
- Last updated
- 24 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: At this time, we do not plan to share individual participant data (IPD) due to concerns regarding patient privacy, the regulatory requirements for data sharing for maintaining patient confidentiality
Publications
Yco LP, Mocz G, Opoku-Ansah J, Bachmann AS. Withaferin A Inhibits STAT3 and Induces Tumor Cell Death in Neuroblastoma and Multiple Myeloma. Biochem Insights. 2014 Nov 9;7:1-13. doi: 10.4137/BCI.S18863. eCollection 2014.
PubMed 25452693Um HJ, Min KJ, Kim DE, Kwon TK. Withaferin A inhibits JAK/STAT3 signaling and induces apoptosis of human renal carcinoma Caki cells. Biochem Biophys Res Commun. 2012 Oct 12;427(1):24-9. doi: 10.1016/j.bbrc.2012.08.133. Epub 2012 Sep 12.
PubMed 22982675Jagasia M, Perales MA, Schroeder MA, Ali H, Shah NN, Chen YB, Fazal S, Dawkins FW, Arbushites MC, Tian C, Connelly-Smith L, Howell MD, Khoury HJ. Ruxolitinib for the treatment of steroid-refractory acute GVHD (REACH1): a multicenter, open-label phase 2 trial. Blood. 2020 May 14;135(20):1739-1749. doi: 10.1182/blood.2020004823.
PubMed 32160294Abboud R, Choi J, Ruminski P, Schroeder MA, Kim S, Abboud CN, DiPersio JF. Insights into the role of the JAK/STAT signaling pathway in graft-versus-host disease. Ther Adv Hematol. 2020 Jun 2;11:2040620720914489. doi: 10.1177/2040620720914489. eCollection 2020.
PubMed 32537114Pires N, Gota V, Gulia A, Hingorani L, Agarwal M, Puri A. Safety and pharmacokinetics of Withaferin-A in advanced stage high grade osteosarcoma: A phase I trial. J Ayurveda Integr Med. 2020 Jan-Mar;11(1):68-72. doi: 10.1016/j.jaim.2018.12.008. Epub 2019 Mar 21.
PubMed 30904387Gupta SK, Jadhav S, Gohil D, Panigrahi GC, Kaushal RK, Gandhi K, Patil A, Chavan P, Gota V. Safety, toxicity and pharmacokinetic assessment of oral Withaferin-A in mice. Toxicol Rep. 2022 May 18;9:1204-1212. doi: 10.1016/j.toxrep.2022.05.012. eCollection 2022.
PubMed 36518386Das R, Rauf A, Akhter S, Islam MN, Emran TB, Mitra S, Khan IN, Mubarak MS. Role of Withaferin A and Its Derivatives in the Management of Alzheimer's Disease: Recent Trends and Future Perspectives. Molecules. 2021 Jun 17;26(12):3696. doi: 10.3390/molecules26123696.
PubMed 34204308Xia Y, Wang P, Yan N, Gonzalez FJ, Yan T. Withaferin A alleviates fulminant hepatitis by targeting macrophage and NLRP3. Cell Death Dis. 2021 Feb 11;12(2):174. doi: 10.1038/s41419-020-03243-w.
PubMed 33574236Vedi M, Sabina EP. Assessment of hepatoprotective and nephroprotective potential of withaferin A on bromobenzene-induced injury in Swiss albino mice: possible involvement of mitochondrial dysfunction and inflammation. Cell Biol Toxicol. 2016 Oct;32(5):373-90. doi: 10.1007/s10565-016-9340-2. Epub 2016 Jun 1.
PubMed 27250656Gambhir L, Checker R, Sharma D, Thoh M, Patil A, Degani M, Gota V, Sandur SK. Thiol dependent NF-kappaB suppression and inhibition of T-cell mediated adaptive immune responses by a naturally occurring steroidal lactone Withaferin A. Toxicol Appl Pharmacol. 2015 Dec 1;289(2):297-312. doi: 10.1016/j.taap.2015.09.014. Epub 2015 Sep 25.
PubMed 26408225Straughn AR, Kakar SS. Withaferin A: a potential therapeutic agent against COVID-19 infection. J Ovarian Res. 2020 Jul 19;13(1):79. doi: 10.1186/s13048-020-00684-x.
PubMed 32684166Mehta M, Gohil D, Khattry N, Kumar R, Sandur S, Sharma D, Checker R, Agarwal B, Jha D, Majumdar A, Gota V. Prevention of acute graft-versus-host-disease by Withaferin a via suppression of AKT/mTOR pathway. Int Immunopharmacol. 2020 Jul;84:106575. doi: 10.1016/j.intimp.2020.106575. Epub 2020 May 13.
PubMed 32416453Shohat B, Gitter S, Lavie D. Effect of withaferin A on Ehrlich ascites tumor cells--cytological observations. Int J Cancer. 1970 Mar 15;5(2):244-52. doi: 10.1002/ijc.2910050212. No abstract available.
PubMed 5449164Lee IC, Choi BY. Withaferin-A--A Natural Anticancer Agent with Pleitropic Mechanisms of Action. Int J Mol Sci. 2016 Mar 4;17(3):290. doi: 10.3390/ijms17030290.
PubMed 26959007Singh N, Bhalla M, de Jager P, Gilca M. An overview on ashwagandha: a Rasayana (rejuvenator) of Ayurveda. Afr J Tradit Complement Altern Med. 2011;8(5 Suppl):208-13. doi: 10.4314/ajtcam.v8i5S.9. Epub 2011 Jul 3.
PubMed 22754076