Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Romidepsin Maintenance After Allogeneic Stem Cell Transplantation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02512497
Recruitment Status : Recruiting
First Posted : July 31, 2015
Last Update Posted : January 7, 2020
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Jonathan Brammer, Ohio State University Comprehensive Cancer Center

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.


Condition or disease Intervention/treatment Phase
Cutaneous T-cell Lymphoma T-Prolymphocytic Leukemia T-Large Granulocytic Leukemia T-Lymphoblastic Leukemia/Lymphoma Peripheral T-Cell Lymphoma Drug: Romidepsin Drug: Busulfan Drug: Fludarabine Procedure: Stem Cell Transplant Drug: Thymoglobulin Phase 1

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Romidepsin Therapy in Conditioning and Maintenance in Patients With T-Cell Malignancies Receiving Allogeneic Stem Cell Transplant
Actual Study Start Date : December 8, 2017
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2020


Arm Intervention/treatment
Experimental: Romidepsin + Busulfan + Fludarabine + Stem Cell Transplant

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

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.

Other Names:
  • Istodax
  • Depsipeptide
  • FK228

Drug: Busulfan
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.
Other Names:
  • Busulfex
  • Myleran

Drug: Fludarabine
Part 1: Fludarabine 40 mg/m2 by vein on Days -6 to -3.
Other Names:
  • Fludarabine Phosphate
  • Fludara

Procedure: Stem Cell Transplant
Stem cell infusion on Day 0.

Drug: Thymoglobulin
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.
Other Names:
  • ATG
  • Rabbit Antithymocyte Globulin
  • Rabbit Antilymphocyte Globulin
  • Rabbit ATG
  • rATG




Primary Outcome Measures :
  1. Toxicity of Romidepsin with Busulfan and Fludarabine Conditioning Therapy for Allogeneic Stem Cell Transplantation [ Time Frame: 30 days ]
    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).

  2. Efficacy of Romidepsin with Busulfan and Fludarabine Conditioning Therapy for Allogeneic Stem Cell Transplantation [ Time Frame: 30 days post allosct ]
    Efficacy defined as the participant being engrafted and alive at day 30 post allosct.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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);
  • Symptomatic coronary artery disease (CAD), e.g., angina Canadian Class II-IV. In any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present;
  • An EKG recorded at screening showing evidence of cardiac ischemia (ST depression depression of >/= 2 mm, measured from isoelectric line to the ST segment). If in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present;
  • Congestive heart failure (CHF) that meets New York Heart Association (NYHA) Class II to IV definitions and/or ejection fraction <40% by MUGA scan or <50% by echocardiogram and/or MRI;
  • A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), Torsade de Pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD);
  • Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes;
  • Uncontrolled hypertension, i.e., blood pressure (BP) of >/= 160/95; patients who have a history of hypertension controlled by medication must be on a stable dose and meet all other inclusion criteria; or,
  • Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers).
  • Patients taking drugs leading to significant QT prolongation where the interaction is too great to proceed with romidepsin.
  • Concomitant use of CYP3A4 inhibitors where the interaction is thought too great to proceed with romidepsin.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02512497


Contacts
Layout table for location contacts
Contact: The Ohio State University Comprehensive Cancer Center 800-293-5066 OSUCCCClinicaltrials@osumc.edu

Locations
Layout table for location information
United States, Ohio
The Ohio State University Cancer Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Samantha Buls       Samantha.Buls@osumc.edu   
Principal Investigator: Jonathan Brammer, MD         
Sponsors and Collaborators
Ohio State University Comprehensive Cancer Center
Celgene Corporation
Investigators
Layout table for investigator information
Principal Investigator: Jonathan Brammer, MD The Ohio State University Comprehensive Cancer Center
Additional Information:
Layout table for additonal information
Responsible Party: Jonathan Brammer, Principal Investigator, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT02512497    
Other Study ID Numbers: OSU-16242
NCI-2015-01555 ( Registry Identifier: NCI CTRP )
First Posted: July 31, 2015    Key Record Dates
Last Update Posted: January 7, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jonathan Brammer, Ohio State University Comprehensive Cancer Center:
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
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Lymphoma, T-Cell, Cutaneous
Leukemia, Prolymphocytic
Leukemia, Myeloid
Leukemia, Prolymphocytic, T-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Leukemia, T-Cell
Vidarabine
Fludarabine
Fludarabine phosphate
Busulfan
Romidepsin
Thymoglobulin
Antilymphocyte Serum
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents