Romidepsin Maintenance After Allogeneic Stem Cell Transplantation

NCT02512497 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-16242NCI-2015-01555
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if giving romidepsin before and after a stem cell transplant in combination with fludarabine and busulfan can help to control leukemia or lymphoma. Researchers also want to learn the highest tolerable dose of romidepsin that can be given with this combination. The safety of this combination and the safety of giving romidepsin after a stem cell transplant will also be studied. This is an investigational study. Romidepsin is FDA approved and commercially available for the treatment of CTCL in patients who have received at least 1 systemic (affecting the whole body) therapy before. Busulfan and fludarabine are FDA approved and commercially available for use with a stem cell transplant. The use of the combination of romidepsin, busulfan, and fludarabine to treat the type of leukemia or lymphoma you have is considered investigational. Up to 30 participants will be enrolled in this study. All will take part at MD Anderson.

Conditions

Cutaneous T-cell Lymphoma; T-Prolymphocytic Leukemia; T-Large Granulocytic Leukemia; T-Lymphoblastic Leukemia/Lymphoma; Peripheral T-Cell Lymphoma

Keywords

Cutaneous T-cell Lymphoma; CTCL; T-Prolymphocytic Leukemia; T-PLL; T-Large Granulocytic Leukemia; T-LGL; T-Lymphoblastic Leukemia/Lymphoma; T-ALL; Peripheral T-Cell Lymphoma; PTCL; Allogeneic stem cell transplantation; Romidepsin; Istodax; Depsipeptide; FK228; Busulfan; Busulfex; Myleran; Fludarabine; Fludarabine phosphate; Fludara

Outcome Measures

Primary Outcomes (2)

• Toxicity of Romidepsin with Busulfan and Fludarabine Conditioning Therapy for Allogeneic Stem Cell Transplantation

  Toxicity defined as death from any cause, grade 3 or 4 graft-versus-host disease, grade 3-4 mucositis lasting for more than 3 days at peak severity, or or grade 3 or 4 non-hematologic non-infectious toxicity within 30 days of receiving the first Romidepsin administration on day -6 (day 24 post allosct).

  30 days

• Efficacy of Romidepsin with Busulfan and Fludarabine Conditioning Therapy for Allogeneic Stem Cell Transplantation

  Efficacy defined as the participant being engrafted and alive at day 30 post allosct.

  30 days post allosct

Study Arms (1)

Romidepsin + Busulfan + Fludarabine + Stem Cell Transplant

EXPERIMENTAL

Part 1: Busulfan administered at the dose calculated to achieve a total (including first two doses delivered on Day -13 and -12) systemic exposure of 20,000 ± 12% µMol-min based on the pharmacokinetic studies. Fludarabine 40 mg/m2 by vein on Days -6 to -3. Romidepsin dosed per actual body weight/actual body surface area. Romidepsin administered on Day -6, -5, -4, and -3 at escalating doses of 1 mg/m2, 2 mg/m2, and 3 mg/m2 by vein to determine the optimal dose. Participants receiving a graft from a matched unrelated donor receive rabbit Thymoglobulin; 0.5 mg/kg on Day -3, 1.5 mg/kg on Day -2 and 2.0 mg/kg on Day -1. Stem cell infusion on Day 0. Romidepsin Maintenance Therapy - Part 2: Starting between Day +28 and Day +100, if participant is eligible based on disease status, they will continue to receive Romidepsin 8 mg/m2 by vein over 1 hour on Day 1 of each 2-week cycle.

Drug: Romidepsin; Drug: Busulfan; Drug: Fludarabine; Procedure: Stem Cell Transplant; Drug: Thymoglobulin

Interventions

Romidepsin DRUG

Part 1: Romidepsin dosed per actual body weight/actual body surface area. Romidepsin administered on Day -6, -5, -4, and -3 at escalating doses of 1 mg/m2, 2 mg/m2, and 3 mg/m2 by vein to determine the maximal tolerated dose. Romidepsin Maintenance Therapy - Part 2: Starting between Day +28 and Day +100, if participant is eligible based on disease status, they will continue to receive Romidepsin 8 mg/m2 by vein over 1 hour on Day 1 of each 2-week cycle.

Also known as: Istodax, Depsipeptide, FK228

Romidepsin + Busulfan + Fludarabine + Stem Cell Transplant

Busulfan DRUG

Part 1: First 2 doses of Busulfan of 80 mg/m2 administered on day -13 and -12. Busulfan administered at the dose calculated to achieve a total (including first two doses delivered on Day -13 and -12) systemic exposure of 20,000 ± 12% µMol-min based on the pharmacokinetic (PK) studies. An additional standard of care (SOC) option is now added for those with an HCT-CI \>4 or deemed unfit by the investigator to receive full dose (AUC 5000 umol-min) Time-Sequential (TS) Busulfan. SOC busulfan is administered per OSU SCT SOP with a targeted AUC of 4000 umol-min/day for a total exposure of 16,000 umol-min +/- 12% u-Mol-min based upon PK studies. Busulfan 'test-dose' PK studies will be performed prior to administration of full dose of busulfan per SOC. Romidepsin and fludarabine will be administered in an identical fashion using the SOC busulfan as with the TS busulfan. TS busulfan method of busulfan administration will be the preferred method of conditioning therapy for patients enrolled.

Also known as: Busulfex, Myleran

Romidepsin + Busulfan + Fludarabine + Stem Cell Transplant

Fludarabine DRUG

Part 1: Fludarabine 40 mg/m2 by vein on Days -6 to -3.

Also known as: Fludarabine Phosphate, Fludara

Romidepsin + Busulfan + Fludarabine + Stem Cell Transplant

Stem Cell Transplant PROCEDURE

Stem cell infusion on Day 0.

Romidepsin + Busulfan + Fludarabine + Stem Cell Transplant

Thymoglobulin DRUG

Participants receiving a graft from a matched unrelated donor receive rabbit Thymoglobulin; 0.5 mg/kg on Day -3, 1.5 mg/kg on Day -2 and 2.0 mg/kg on Day -1.

Also known as: ATG, Rabbit Antithymocyte Globulin, Rabbit Antilymphocyte Globulin, Rabbit ATG, rATG

Romidepsin + Busulfan + Fludarabine + Stem Cell Transplant

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 70 years of age.
• Diagnosis of either Cutaneous T-Cell Lymphoma; T-Prolymphocytic Leukemia; T-Large Granulocytic Leukemia; T-Lymphoblastic Leukemia/lymphoma; or Peripheral T-Cell Lymphoma, Natural Killer/T-cell lymphoma for whom allogeneic stem cell transplantation is indicated.
• An 10/10 or 8/8 HLA matched (high resolution typing at A, B, C, DRB1, DQ1) sibling or unrelated donor.
• EF\>/= 50% on MUGA scan or Echocardiogram.
• FEV1, FVC and corrected DLCO \>/= 40%.
• Adequate renal function, as defined by estimated serum creatinine clearance \>/=50 ml/min (using the Cockcroft-Gault formula: creatinine clearance = \[(140-age)\*kg/(72\*serum creatinine)\] \* 0.85 if female) and/or serum creatinine \</=1.6 mg/dL. Renal function will be calculated using ideal body weight (IBW), unless a patient weights \>40% of their IBW, then adjusted body weight will be utilized.
• Serum bilirubin \</= 1.5 x upper limit of normal.
• SGOT and SGPT \</= 2 x upper limit of normal.
• Able to sign informed consent.
• Men and women of reproductive potential must agree to follow accepted birth control methods for the duration of the study. Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. Male subject agrees to use an acceptable method for contraception for the duration of the study.

You may not qualify if:

• Patient with active CNS disease.
• Pregnancy (positive Beta HCG test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization) or currently breast-feeding. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
• Active hepatitis B, either active carrier (HBsAg +) or viremic (HBV DNA \>/=10,000 copies/mL, or \>/= 2,000 IU/mL).
• Evidence of either cirrhosis or stage 3-4 liver fibrosis in patients with chronic hepatitis C or positive hepatitis C serology.
• HIV infection.
• Hematopoetic Transplant Co-Morbidity Index (HCT-CI) \>4 unless deemed clinically insignificant by primary investigator for patients receiving Time-Sequential Busulfan (total exposure 20000 umol-min).
• Active uncontrolled bacterial, viral or fungal infections.
• Exposure to other investigational drugs within 4 weeks before enrollment.
• Grade \>/= 3 non-hematologic toxicity from previous therapy that has not resolved to \</= grade 1.
• Radiation therapy to head and neck (excluding eyes), and internal organs of chest, abdomen or pelvis in the month prior to enrollment.
• Prior whole brain irradiation.
• Prior autologous SCT in the prior 12 months.
• Congenital QT syndrome, QTc \>500 ms.
• Myocardial infarction within 1 year of study entry. Subjects with a history of myocardial infarction between 6 and 12 months prior to study entry who are asymptomatic and have had a negative cardiac risk assessment (treadmill stress test, nuclear medicine stress test, or stress echocardiogram) since the event may participate;
• Other significant EKG abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min);

Sponsors & Collaborators

• Ohio State University Comprehensive Cancer Center: lead
• Celgene Corporation: collaborator

Study Sites (1)

The Ohio State University Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Links

• The Jamesline

MeSH Terms

Conditions

Lymphoma, T-Cell, Cutaneous; Leukemia, Prolymphocytic, T-Cell; Lymphoma; Lymphoma, T-Cell, Peripheral; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Interventions

romidepsin; Depsipeptides; Busulfan; fludarabine; fludarabine phosphate; Stem Cell Transplantation; thymoglobulin

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Prolymphocytic; Leukemia, Lymphoid; Leukemia; Leukemia, T-Cell; Hematologic Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Jonathan Brammer, MD

  The Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 29, 2015
• First Posted: July 31, 2015
• Study Start: December 8, 2017
• Primary Completion: October 6, 2023
• Study Completion: June 18, 2025
• Last Updated: September 19, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)