Study of Standardized Withaferin-A for the Treatment of Steroid Refractory Acute Graft Versus Host Disease.

NCT07708987 | Recruiting Phase 2 DMC

• 1 other identifier: 900937
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief 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) 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.

Conditions

Hematological Malignancy; GVHD - Graft-Versus-Host Disease; Steriod Refractory

Keywords

Withaferin A

Outcome Measures

Primary Outcomes (1)

• OBJECTIVE RESPONSE RATE (ORR)

  OBJECTIVE RESPONSE RATE (ORR)

  Day 28 after initiation of standardized Withaferin A (SWA)

Secondary Outcomes (6)

• Overall response rate

  Day 14 and Day 56 after initiation of standardized Withaferin A

• Non-relapse mortality (NRM)

  Up to 1 year post-transplant

• Overall survival (OS)

  Up to 1 year post-transplant

• Incidence of chronic graft versus host disease

  Up to 1 year post-transplant

• Incidence of adverse effects

  until 12 weeks after last dose of Investigational product

Other Outcomes (6)

• Number of participants with a ≥30% reduction in corticosteroid dose from baseline

  Day 28 after initiation of standardized Withaferin A(SWA).

• Change in JAK2 and STAT3 biomarker levels from baseline

  Baseline (before initiation of SWA), Day +7 and Day +28 after initiation of SWA.

• Change in JAK2-STAT3 receptor kinetics from baseline

  Baseline (before initiation of SWA), Day +7 and Day +28 after initiation of SWA.

Study Arms (1)

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.

Drug: Standardized Withaferin A (SWA)

Interventions

Standardized Withaferin A (SWA) DRUG

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

Standardized Withaferin A (SWA)

Eligibility Criteria

• Age: 12 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tata Memorial Centre: lead

Study Sites (1)

Advanced Centre for Treatment, Research and Education in Cancer

Navi Mumbai, Maharashtra, 410210, India

RECRUITING

Related Publications (18)

• 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.

  PMID: 22510383 BACKGROUND

• Pires 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.

  PMID: 30904387 RESULT

• Mehta 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.

  PMID: 32416453 RESULT

• Jagasia 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.

  PMID: 32160294 RESULT

• Socie 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.

  PMID: 27899357 RESULT

• Zeiser 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.

  PMID: 29171820 RESULT

• Martin 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.

  PMID: 22510384 RESULT

• Dignan 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.

  PMID: 22533831 RESULT

• Westin 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.

  PMID: 22110505 RESULT

• Ruutu 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.

  PMID: 23892326 RESULT

• Shohat 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.

  PMID: 5449164 RESULT

• Gambhir 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.

  PMID: 26408225 RESULT

• Przepiorka 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.

  PMID: 32043777 RESULT

• Rizvi TF, Razauddin M, Rahman SR. Immunomodulatory effect of Ashwagandha against doxorubicin toxicity. Eur J Pharma Med Res. 2016;3:463-7.

  RESULT

• 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.

  PMID: 11301861 RESULT

• Schroeder MA, DiPersio JF. Mouse models of graft-versus-host disease: advances and limitations. Dis Model Mech. 2011 May;4(3):318-33. doi: 10.1242/dmm.006668.

  PMID: 21558065 RESULT

• Ferrara JL, Levine JE, Reddy P, Holler E. Graft-versus-host disease. Lancet. 2009 May 2;373(9674):1550-61. doi: 10.1016/S0140-6736(09)60237-3. Epub 2009 Mar 11.

  PMID: 19282026 RESULT

• Qian L, Wu Z, Shen J. Advances in the treatment of acute graft-versus-host disease. J Cell Mol Med. 2013 Aug;17(8):966-75. doi: 10.1111/jcmm.12093. Epub 2013 Jun 26.

  PMID: 23802653 RESULT

MeSH Terms

Conditions

Hematologic Neoplasms; Graft vs Host Disease

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Immune System Diseases

Study Officials

• Dr.Akanksha Chichra, DNB

  Advanced Centre for Treatment, Research and Education in Cancer

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dr Akanksha Chichra, DNB

CONTACT

27405000; akanksha7@hotmail.com

Dr.Sachin Punatar, DM

CONTACT

27405000; drsachin_punatar@yahoo.in

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: FNB DNB Pediatric oncologist

Model Details: 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.

Study Record Dates

• First Submitted: September 15, 2023
• First Posted: July 16, 2026
• Study Start: September 23, 2023
• Primary Completion (Estimated): January 9, 2028
• Study Completion (Estimated): September 25, 2028
• Last Updated: July 16, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)