Hematological MalignancyPhase 2Withaferin_ANCT07708987
Study of Standardized Withaferin-A for the Treatment of Steroid Refractory Acute Graft Versus Host Disease.
A Phase 2 study testing Standardized Withaferin A (SWA) in people with Hematological Malignancy and GVHD - Graft-Versus-Host Disease, run by Tata Memorial Centre at 1 site in India.
Trial summary
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)… Read more about this study
- Who is it for?
- Ages 12 to 65 years
- Conditions the study is for
- Hematological Malignancy, GVHD - Graft-Versus-Host Disease, Steriod Refractory
- What is being tested?
- Standardized Withaferin A (SWA)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteIndia
- Study dates
- 23 Sep 2023to 25 Sep 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 12 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients age ≥ 12 years with a hematological malignancy who have undergone allogeneic stem cell transplant with matched related donor (MRD), Haploidentical (Haplo) donor or matched unrelated donor (MUD)
- Evidence of myeloid engraftment (eg, absolute neutrophil count ≥0.5 × 109 /L for 3 consecutive days)
- ECOG performance score of 0 or 1
- Patients with steroid-refractory aGvHD, defined as any of the following:
- Patients with progressive GvHD (ie, increase in stage in any organ system or any new organ involvement) after 3 days of primary treatment with methylprednisolone ≥2 mg/kg/d (or equivalent)
- Patients with GvHD that has not improved (ie, decrease in stage in at least 1 involved organ system) after 7 days of primary treatment with methylprednisolone ≥2 mg/kg/d (or equivalent)
- Patients who previously began corticosteroid therapy at a lower dose (≥1 mg/kg/d methylprednisolone) for treatment of skin GvHD or skin GvHD accompanied by upper gut GvHD but develop new GvHD in another organ system
- Patients who cannot tolerate a corticosteroid taper, that is, begin corticosteroids at 2.0 mg/kg/d, demonstrate response, but progress before a 50% decrease from the initial starting dose of corticosteroids is achieved
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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
India1 site, 1 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
About this study
Official title: A Phase II Clinical Trial of Standardized Withaferin-A for the Treatment of Steroid Refractory Acute Graft Versus Host Disease
Study Design Prospective, single center, single arm, Phase II study.
Research aims and objectives Aim:
Read more
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:
- 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.
- Dose adjustments/modifications: If the patient experiences any grade ≥3 toxicities related to SWA, further administration of SWA will be withheld immediately. Once the severity of the adverse event reduces to grade ≤1, the study agent will be rechallenged with 25% dose reduction. The same strategy will be adopted for successive grade ≥3 toxicities. If the drug is not tolerated at 25% of original dose (100 mg), no further rechallenge will be attempted.
- Corticosteroid tapering will be done as per the treating physician's discretion and clinical condition of the patient.
Read the detailed description
Secondary Objectives:
- To evaluate the ORR at other defined time points (Day 14 and Day 56) from initiation of SWA
- To study the Non relapse Mortality (NRM) at 1 year post transplant
- To study the Relapse rate at 1 year post transplant
- To study the Overall Survival (OS) at 1 year post transplant
- To study the incidence of chronic GvHD at 1 year post transplant
- To study the incidence of adverse effects attributed to SWA
Exploratory Objectives:
- Reduction of steroid dose by ≥30% from baseline will be calculated for all patients on day 28 after start of SWA.
- To measure the JAK2-STAT3 levels, JAK2-STAT3 receptor kinetics at baseline (pre- conditioning) and post initiation of WA.
- Immune cell phenotype, cytokine profile and pharmacokinetics of WA in patients post treatment with SWA at baseline, Day +7, Day +14, Day +28, Day+56, Day+90 and Day +180 post HSCT.
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.
- Being tested
- Standardized Withaferin A (SWA)
- Keywords
- Withaferin A
- Medical subject headings
- Hematologic Neoplasms, Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standardized Withaferin A (SWA)Drug
Also called root extract of Withania somnifera
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.
| Study group | Role | What they receive |
|---|---|---|
| Standardized Withaferin A (SWA) | Experimental | 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. Receives: Drug: Standardized Withaferin A (SWA) |
What is being measured
The primary outcome is the main question the study is designed to answer.
OBJECTIVE RESPONSE RATE (ORR)
OBJECTIVE RESPONSE RATE (ORR)
Measured: Day 28 after initiation of standardized Withaferin A (SWA)
Secondary outcomes (6)
Overall response rate
Overall response rate at Day 14 and Day 56
Measured: 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.
Measured: Up to 1 year post-transplant
Overall survival (OS)
The overall survival (OS) at 1 year post transplant
Measured: 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.
Measured: Up to 1 year post-transplant
Incidence of adverse effects
The incidence of adverse effects attributed to standardized Withaferin A (SWA).
Measured: until 12 weeks after last dose of Investigational product
Relapse rate
Relapse rate 1 year post transplant
Measured: upto 1 year post transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2026
- Study start23 Sep 2023
- Primary completion9 Jan 2028 (estimated)
- Study completion25 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (18)Papers the sponsor has linked to this study.
- Other trials for Hematological MalignancyStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Withaferin A ((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.
- Masking
- None (open label)
- Enrolment
- 34 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tata Memorial Centre
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Akanksha Chichra, Tata Memorial Centre
- Investigators
- Dr.Akanksha Chichra, DNB, Principal investigator, Advanced Centre for Treatment, Research and Education in Cancer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07708987
- Sponsor's protocol ID
- 900937
- Acronym
- Withaferin_A
- Status last verified
- Jul 2026
- First submitted
- 15 Sep 2023
- Last updated
- 16 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: IP details not shared
Publications
Martin PJ, Inamoto Y, Flowers ME, Carpenter PA. Secondary treatment of acute graft-versus-host disease: a critical review. Biol Blood Marrow Transplant. 2012 Jul;18(7):982-8. doi: 10.1016/j.bbmt.2012.04.006. Epub 2012 Apr 14.
PubMed 22510383Pires 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 30904387Mehta 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 32416453Jagasia 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 32160294Socie G, Vigouroux S, Yakoub-Agha I, Bay JO, Furst S, Bilger K, Suarez F, Michallet M, Bron D, Gard P, Medeghri Z, Lehert P, Lai C, Corn T, Vernant JP. A phase 3 randomized trial comparing inolimomab vs usual care in steroid-resistant acute GVHD. Blood. 2017 Feb 2;129(5):643-649. doi: 10.1182/blood-2016-09-738625. Epub 2016 Nov 29.
PubMed 27899357Zeiser R, Blazar BR. Acute Graft-versus-Host Disease - Biologic Process, Prevention, and Therapy. N Engl J Med. 2017 Nov 30;377(22):2167-2179. doi: 10.1056/NEJMra1609337. No abstract available.
PubMed 29171820Martin PJ, Rizzo JD, Wingard JR, Ballen K, Curtin PT, Cutler C, Litzow MR, Nieto Y, Savani BN, Schriber JR, Shaughnessy PJ, Wall DA, Carpenter PA. First- and second-line systemic treatment of acute graft-versus-host disease: recommendations of the American Society of Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2012 Aug;18(8):1150-63. doi: 10.1016/j.bbmt.2012.04.005. Epub 2012 Apr 14.
PubMed 22510384Dignan FL, Clark A, Amrolia P, Cornish J, Jackson G, Mahendra P, Scarisbrick JJ, Taylor PC, Hadzic N, Shaw BE, Potter MN; Haemato-oncology Task Force of British Committee for Standards in Haematology; British Society for Blood and Marrow Transplantation. Diagnosis and management of acute graft-versus-host disease. Br J Haematol. 2012 Jul;158(1):30-45. doi: 10.1111/j.1365-2141.2012.09129.x. Epub 2012 Apr 26.
PubMed 22533831Westin JR, Saliba RM, De Lima M, Alousi A, Hosing C, Qazilbash MH, Khouri IF, Shpall EJ, Anderlini P, Rondon G, Andersson BS, Champlin R, Couriel DR. Steroid-Refractory Acute GVHD: Predictors and Outcomes. Adv Hematol. 2011;2011:601953. doi: 10.1155/2011/601953. Epub 2011 Nov 3.
PubMed 22110505Ruutu T, Gratwohl A, de Witte T, Afanasyev B, Apperley J, Bacigalupo A, Dazzi F, Dreger P, Duarte R, Finke J, Garderet L, Greinix H, Holler E, Kroger N, Lawitschka A, Mohty M, Nagler A, Passweg J, Ringden O, Socie G, Sierra J, Sureda A, Wiktor-Jedrzejczak W, Madrigal A, Niederwieser D. Prophylaxis and treatment of GVHD: EBMT-ELN working group recommendations for a standardized practice. Bone Marrow Transplant. 2014 Feb;49(2):168-73. doi: 10.1038/bmt.2013.107. Epub 2013 Jul 29.
PubMed 23892326Shohat 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 5449164Gambhir 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 26408225Przepiorka D, Luo L, Subramaniam S, Qiu J, Gudi R, Cunningham LC, Nie L, Leong R, Ma L, Sheth C, Deisseroth A, Goldberg KB, Blumenthal GM, Pazdur R. FDA Approval Summary: Ruxolitinib for Treatment of Steroid-Refractory Acute Graft-Versus-Host Disease. Oncologist. 2020 Feb;25(2):e328-e334. doi: 10.1634/theoncologist.2019-0627. Epub 2019 Oct 22.
PubMed 32043777Rizvi TF, Razauddin M, Rahman SR. Immunomodulatory effect of Ashwagandha against doxorubicin toxicity. Eur J Pharma Med Res. 2016;3:463-7.
Furmanowa M, Gajdzis-Kuls D, Ruszkowska J, Czarnocki Z, Obidoska G, Sadowska A, Rani R, Upadhyay SN. In vitro propagation of Withania somnifera and isolation of withanolides with immunosuppressive activity. Planta Med. 2001 Mar;67(2):146-9. doi: 10.1055/s-2001-11494.
PubMed 11301861
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Clinical Trial of Standardized Withaferin-A for the Treatment of Steroid Refractory Acute Graft Versus Host Disease
- ClinicalTrials.gov ID
- NCT07708987
- Acronym / sponsor ID
- Withaferin_A / 900937
- Keywords
- Withaferin A
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 34 participants (estimated)
- Lead sponsor
- Tata Memorial CentreUniversity, hospital or other
- Study start
- 23 Sep 2023 (actual)
- Primary completion
- 9 Jan 2028 (estimated)
- Study completion
- 25 Sep 2028 (estimated)
- First posted
- 16 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
- Dose adjustments/modifications: If the patient experiences any grade ≥3 toxicities related to SWA, further administration of SWA will be withheld immediately. Once the severity of the adverse event reduces to grade ≤1, the study agent will be rechallenged with 25% dose reduction. The same strategy will be adopted for successive grade ≥3 toxicities. If the drug is not tolerated at 25% of original dose (100 mg), no further rechallenge will be attempted.
- Corticosteroid tapering will be done as per the treating physician's discretion and clinical condition of the patient.
Detailed description
Secondary Objectives:
- To evaluate the ORR at other defined time points (Day 14 and Day 56) from initiation of SWA
- To study the Non relapse Mortality (NRM) at 1 year post transplant
- To study the Relapse rate at 1 year post transplant
- To study the Overall Survival (OS) at 1 year post transplant
- To study the incidence of chronic GvHD at 1 year post transplant
- To study the incidence of adverse effects attributed to SWA
Exploratory Objectives:
- Reduction of steroid dose by ≥30% from baseline will be calculated for all patients on day 28 after start of SWA.
- To measure the JAK2-STAT3 levels, JAK2-STAT3 receptor kinetics at baseline (pre- conditioning) and post initiation of WA.
- Immune cell phenotype, cytokine profile and pharmacokinetics of WA in patients post treatment with SWA at baseline, Day +7, Day +14, Day +28, Day+56, Day+90 and Day +180 post HSCT.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Withaferin A ((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.
| Arm | Type | Receives |
|---|---|---|
| Standardized Withaferin A (SWA) | Experimental | Drug: Standardized Withaferin A (SWA)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. |
Who may qualify
- Ages
- 12 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Patients age ≥ 12 years with a hematological malignancy who have undergone allogeneic stem cell transplant with matched related donor (MRD), Haploidentical (Haplo) donor or matched unrelated donor (MUD)
- Evidence of myeloid engraftment (eg, absolute neutrophil count ≥0.5 × 109 /L for 3 consecutive days)
- ECOG performance score of 0 or 1
- Patients with steroid-refractory aGvHD, defined as any of the following:
- Patients with progressive GvHD (ie, increase in stage in any organ system or any new organ involvement) after 3 days of primary treatment with methylprednisolone ≥2 mg/kg/d (or equivalent)
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standardized Withaferin A (SWA)Also: root extract of Withania somniferaWithaferin-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. | Drug | Standardized Withaferin A (SWA) |
Primary outcome
OBJECTIVE RESPONSE RATE (ORR)
Time frame: Day 28 after initiation of standardized Withaferin A (SWA)
OBJECTIVE RESPONSE RATE (ORR)
6 secondary outcomes
Overall response rate
Time frame: Day 14 and Day 56 after initiation of standardized Withaferin A
Non-relapse mortality (NRM)
Time frame: Up to 1 year post-transplant
Overall survival (OS)
Time frame: Up to 1 year post-transplant
Incidence of chronic graft versus host disease
Time frame: Up to 1 year post-transplant
Incidence of adverse effects
Time frame: until 12 weeks after last dose of Investigational product
Relapse rate
Time frame: upto 1 year post transplant
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2026.
- Background: PubMed 22510383Martin PJ, Inamoto Y, Flowers ME, Carpenter PA. Secondary treatment of acute graft-versus-host disease: a critical review. Biol Blood Marrow Transplant. 2012 Jul;18(7):982-8. doi: 10.1016/j.bbmt.2012.04.006. Epub 2012 Apr 14.
- Results publication: PubMed 30904387Pires 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.
- Results publication: PubMed 32416453Mehta 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.
- Results publication: PubMed 32160294Jagasia 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.
- Results publication: PubMed 27899357Socie G, Vigouroux S, Yakoub-Agha I, Bay JO, Furst S, Bilger K, Suarez F, Michallet M, Bron D, Gard P, Medeghri Z, Lehert P, Lai C, Corn T, Vernant JP. A phase 3 randomized trial comparing inolimomab vs usual care in steroid-resistant acute GVHD. Blood. 2017 Feb 2;129(5):643-649. doi: 10.1182/blood-2016-09-738625. Epub 2016 Nov 29.
- Results publication: PubMed 29171820Zeiser R, Blazar BR. Acute Graft-versus-Host Disease - Biologic Process, Prevention, and Therapy. N Engl J Med. 2017 Nov 30;377(22):2167-2179. doi: 10.1056/NEJMra1609337. No abstract available.
- Results publication: PubMed 22510384Martin PJ, Rizzo JD, Wingard JR, Ballen K, Curtin PT, Cutler C, Litzow MR, Nieto Y, Savani BN, Schriber JR, Shaughnessy PJ, Wall DA, Carpenter PA. First- and second-line systemic treatment of acute graft-versus-host disease: recommendations of the American Society of Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2012 Aug;18(8):1150-63. doi: 10.1016/j.bbmt.2012.04.005. Epub 2012 Apr 14.
- Results publication: PubMed 22533831Dignan FL, Clark A, Amrolia P, Cornish J, Jackson G, Mahendra P, Scarisbrick JJ, Taylor PC, Hadzic N, Shaw BE, Potter MN; Haemato-oncology Task Force of British Committee for Standards in Haematology; British Society for Blood and Marrow Transplantation. Diagnosis and management of acute graft-versus-host disease. Br J Haematol. 2012 Jul;158(1):30-45. doi: 10.1111/j.1365-2141.2012.09129.x. Epub 2012 Apr 26.
- Results publication: PubMed 22110505Westin JR, Saliba RM, De Lima M, Alousi A, Hosing C, Qazilbash MH, Khouri IF, Shpall EJ, Anderlini P, Rondon G, Andersson BS, Champlin R, Couriel DR. Steroid-Refractory Acute GVHD: Predictors and Outcomes. Adv Hematol. 2011;2011:601953. doi: 10.1155/2011/601953. Epub 2011 Nov 3.
- Results publication: PubMed 23892326Ruutu T, Gratwohl A, de Witte T, Afanasyev B, Apperley J, Bacigalupo A, Dazzi F, Dreger P, Duarte R, Finke J, Garderet L, Greinix H, Holler E, Kroger N, Lawitschka A, Mohty M, Nagler A, Passweg J, Ringden O, Socie G, Sierra J, Sureda A, Wiktor-Jedrzejczak W, Madrigal A, Niederwieser D. Prophylaxis and treatment of GVHD: EBMT-ELN working group recommendations for a standardized practice. Bone Marrow Transplant. 2014 Feb;49(2):168-73. doi: 10.1038/bmt.2013.107. Epub 2013 Jul 29.
- Results publication: PubMed 5449164Shohat 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.
- Results publication: PubMed 26408225Gambhir 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.
- Individual participant dataSharing planned: No. IP details not shared
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Dr.Akanksha Chichra, DNB principal investigator
Advanced Centre for Treatment, Research and Education in Cancer
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Standardized Withaferin A (SWA) in people with Hematological Malignancy and GVHD - Graft-Versus-Host Disease, run by Tata Memorial Centre at 1 site in India.
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 3 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: looking for participants now, as of the sponsor's last update on 16 Jul 2026. 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 India. 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 phase mean?
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Dr Akanksha Chichra, DNB (27405000 ext. 5404, akanksha7@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
OBJECTIVE RESPONSE RATE (ORR) (time frame: Day 28 after initiation of standardized Withaferin A (SWA)). 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 NCT07708987, which also lists 18 linked publications.
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 16 Jul 2026.