A Phase 2 interventional study of Standardized Withaferin A (SWA) in Hematological Malignancy, GVHD - Graft-Versus-Host Disease and Steriod Refractory, sponsored by Tata Memorial Centre. Recruiting at 1 site in India. Open to participants aged 12 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-07-16.
Sponsored by Tata Memorial Centre · Phase 2, Interventional, and Treatment
Study Design Prospective, single center, single arm, Phase II study.
Research aims and objectives Aim:
To evaluate the efficacy and safety of standardized Withaferin A in steroid refractory acute GvHD in patients post allogeneic stem cell transplantation
Primary Objective:
To evaluate the objective Response Rate (ORR) at Day 28 from the start of SWA defined as the proportion of patients achieving Complete Response (CR), Very Good Partial Response (VGPR) or Partial Response (PR).
Methodology
Treatment plan and Interventions Administration of study treatment Name of the intervention: Standardized WA (standardized root extract of Withania somnifera. This will be provided free of cost to the trial patients.
Formulation: The standardized root extract of W. somnifera contains 5% of WA w/w. SWA is available as a 500 mg capsule (AshwaMAX) that contains 25 mg of WA.
Route of administration: Per-oral (P/O) Dose schedule: The dose of SWA is 1500mg/day. It will be administered as 3 capsules of 500 mg once a day.
Duration of treatment:
Secondary Objectives:
Exploratory Objectives:
What is acute Graft versus host disease (GvHD)? GvHD is a complication that can occur after an allogeneic stem cell transplant resulting in damage to internal organs. Patients with GvHD have a mortality rate of 15-40%. In GvHD, the donated bone marrow or peripheral blood stem cells view the recipient's body as foreign, and the donated cells/bone marrow harm the body. Acute GvHD usually develops in the skin, liver or gastrointestinal tract, and symptoms might appear within weeks after transplant. Symptoms of acute GvHD are 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 steroid refractory acute GvHD (SR GvHD)? Most of patients who develop acute GvHD are successfully treated with corticosteroids, a type of medicine that suppress the donor cells from attacking the recipient's organs. If steroids are unsuccessful, it is termed as acute SR GvHD. Acute SR GvHD is a condition with poor outcomes as effective treatments are not available.
What is the current treatment for SR GvHD? The only treatment that is US-FDA approved for the treatment of SR GvHD is ruxolitinib. Ruxolitinib is expensive and hence not affordable for most patients. It also has its own set of side effects which include low blood counts. Although, there are other medicines that have shown to be effective in this condition, none of them have been approved by the regulatory authorities.
What is standardized Withaferin-A (SWA)? Withaferin-A (WA) is the principal 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 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, SR GvHD is a difficult complication of allogeneic stem cell transplant which can lead to increased hospital stay and deaths post-transplant. The only approved drug for steroid refractory GvHD (Ruxolitinib) is expensive and out of reach for most patients. It also has side effects which can lead to its discontinuation. SWA is an oral formulation of WA which seems to be beneficial in the early studies done in the Clinical Pharmacology Laboratory. SWA has also been found to be safe at very high doses. Whether SWA will actually patients undergoing allogeneic stem cell transplant who develop SR GvHD has not been proven as this can only be done by conducting a systematic trial. This trial is being conducted to see if SWA is beneficial in SR GvHD which will give us a drug which is easily available, oral and inexpensive to treat SR GvHD.
How will SWA be given? Patients who agree to participate in this trial and are found to be eligible will be given SWA as a capsule at a dose of 1500 mg/day orally. The drug will be given for a total duration of 12 weeks after which the dose will be reduced and stopped. 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, checking immune cell profile and cytokines (which are markers of your immunity levels) will be done at baseline, Day+7, Day +14, Day+28, Day+56, Day+90, Day +180 from the start of SWA
. What are the risks involved in participation? According to available literature and information, SWA is a safe and well tolerated drug. There is a possibility that rifaximin can have interaction with cyclosporine (immunosuppressant) and antifungal (Azole) drugs which are used in BMT, although studies done in bone marrow transplant (BMT) with rifaximin have not documented such an interaction. Drug levels of azole antifungals and cyclosporine in the blood are monitored as a standard of care (i.e. these will be done irrespective of the decision to take part in this study) in BMT which will help to take corrective action in case there is such an interaction, which will mitigate any potential risk due to this.
What is the possible impact of this trial? If indeed SWA works and treats SR GvHD effectively then this could be a major breakthrough in treatment. It would help many patients who develop SR 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.
1,464 studies on the registry are indexed under Hematologic Neoplasms; 433 are open to participants now.
This study's planned enrollment of 34 is below the median of 45 across 1,068 interventional studies indexed under Hematologic Neoplasms.
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Exclusion Criteria:
Withaferin-A Standardized WA (standardized root extract of Withania somnifera Dose schedule: The dose of SWA is 1500mg/day. It will be administered as 3 capsules of 500 mg once a day. Route :Oral Duration: Every patient will receive treatment for at least 12 weeks followed by a taper as per physician's discretion. WA can be tapered after 12 weeks if the patient has achieved CR or VGPR and has discontinued corticosteroids for at least 4 weeks.
Drug: Standardized Withaferin A (SWA)
Withaferin-A (standardized root extract of Withania somnifera ) Route of administration: Per-oral (P/O) Dose schedule: The dose of SWA is 1500mg/day. It will be administered as 3 capsules of 500 mg once a day. Duration of treatment Every patient will receive treatment for at least 12 weeks followed by a taper as per physician's discretion. WA can be tapered after 12 weeks if the patient has achieved CR or VGPR and has discontinued corticosteroids for at least 4 weeks.
Also known as: root extract of Withania somnifera
OBJECTIVE RESPONSE RATE (ORR)
OBJECTIVE RESPONSE RATE (ORR)
Time frame: Day 28 after initiation of standardized Withaferin A (SWA)
Overall response rate
Overall response rate at Day 14 and Day 56
Time frame: Day 14 and Day 56 after initiation of standardized Withaferin A
Non-relapse mortality (NRM)
The non-relapse mortality (NRM) at 1 year post transplant.
Time frame: Up to 1 year post-transplant
Overall survival (OS)
The overall survival (OS) at 1 year post transplant
Time frame: Up to 1 year post-transplant
Incidence of chronic graft versus host disease
The incidence of chronic graft versus host disease (GVHD) at 1 year post transplant.
Time frame: Up to 1 year post-transplant
Incidence of adverse effects
The incidence of adverse effects attributed to standardized Withaferin A (SWA).
Time frame: until 12 weeks after last dose of Investigational product
Relapse rate
Relapse rate 1 year post transplant
Time frame: upto 1 year post transplant
Number of participants with a ≥30% reduction in corticosteroid dose from baseline
Number of participants achieving a reduction of ≥30% in corticosteroid dose from baseline after initiation of standardized Withaferin A (SWA).
Time frame: Day 28 after initiation of standardized Withaferin A(SWA).
Change in JAK2 and STAT3 biomarker levels from baseline
Change in JAK2 and STAT3 biomarker levels from baseline (before initiation of standardized Withaferin A \[SWA\])
Time frame: Baseline (before initiation of SWA), Day +7 and Day +28 after initiation of SWA.
Change in JAK2-STAT3 receptor kinetics from baseline
Change in JAK2-STAT3 receptor kinetics from baseline (before initiation of standardized Withaferin A \[SWA\])
Time frame: Baseline (before initiation of SWA), Day +7 and Day +28 after initiation of SWA.
Change in immune cell subset frequencies from baseline
Change in the frequency of predefined immune cell subsets
Time frame: Baseline, Day +7 , Day +14 ,Day +28 , and Day +100 post hematopoietic stem cell transplantation (HSCT)
Change in serum cytokine concentrations from baseline
Change in the concentrations of the predefined cytokines from baseline
Time frame: Baseline, Day +7 , Day +14 , Day +28, and Day +100 post transplant
Maximum plasma concentration (Cmax) of Withaferin A
Maximum observed plasma concentration (Cmax) of Withaferin A following administration of standardized Withaferin A (SWA).
Time frame: Pharmacokinetic sampling time points from baseline through Day +100 , post transplant
Plan to share: No — IP details not shared
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