|Romidepsin Maintenance After Allogeneic Stem Cell Transplantation|
|Clinicaltrials.gov identifier||recruitment status||First Posted||Last update posted|
|NCT02512497||Recruiting||July 31, 2015||January 7, 2020|
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:||
Cutaneous T-cell Lymphoma
T-Large Granulocytic Leukemia
Peripheral T-Cell Lymphoma
Procedure: Stem Cell Transplant
Study Parts and Study Drug Dose Levels:
If you are found to be eligible to take part in this study, you will start Part 1 of the
The dose of romidepsin you receive will depend on when you join this study. The first group
All participants will receive the same dose level of fludarabine. Busulfan dose levels are
Study Drug Administration and Transplant (Part 1):
The days before you receive the stem cell transplant are called minus days. The day you
On Days -13 and -12, you will receive busulfan by vein over 3 hours. Blood (about 1 teaspoon
A heparin lock line will be placed in your vein before the PK testing to lower the number of
On Day -7, you will be admitted to the hospital.
On Day -6 through -3, you will receive romidepsin by vein over 4 hours, fludarabine by vein
If you are going to be receiving a transplant from a matched unrelated donor, you will also
Beginning on Day -2, you will receive tacrolimus by vein over 24 hours every day until you
On Day 0, you will receive the donor's stem cells by vein. The infusion will last anywhere
On Days +1, +3, +6, and +11, you will receive methotrexate by vein over about 15 minutes.
If the doctor thinks it is needed, you will be given other standard drugs to help lower the
Romidepsin Maintenance Therapy (Part 2):
Starting between Day +28 and Day +100, if you are eligible for Part 2 based on the disease
As a baseline test at the beginning of the study (within 7 days before starting romidepsin),
You will remain in the hospital for as long as the doctor thinks is needed.
Whenever your doctor thinks it is needed, blood (about 2 tablespoons) and/or urine will be
About ½-1, 3, 6, and 12 months after the transplant:
- You will have a physical exam.
- Blood (about 8 tablespoons) will be drawn to see how well the transplant has taken and
- If the doctor thinks it is needed, you will have a bone marrow aspiration to check the
The above tests/procedures may be performed sooner, if your doctor thinks they are needed.
Before your first dose of romidepsin in Parts 1 and 2:
- You will have an electrocardiogram (EKG) to check your heart function.
- Blood (about 4 tablespoons) will be drawn to learn if and how romidepsin may have
If you are in Part 2, every 2 weeks (before each dose of romidepsin), blood (about 4
If you are in Part 2, once a month:
- You will have an EKG.
- You will have a physical exam.
Part 2 participants may have the blood tests done before each romidepsin dose and monthly
Length of Study:
You may receive up to 4 doses of romidepsin in Part 1. You may also receive chemotherapy on
Your participation on the study will be over after the follow-up visits. After 1 year, you
You may be taken off study early if the doctor thinks it is in your best interest, if the
If for any reason you want to leave the study early, you must talk to the study doctor. It
|Arms and interventions|
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.
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.
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.
Part 1: Fludarabine 40 mg/m2 by vein on Days -6 to -3.
Procedure: Stem Cell Transplant
Stem cell infusion on Day 0.
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.
|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.
|Ages Eligible for Study:||18 to 70 Years (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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 40% of their IBW, then adjusted body weight will be utilized.
- Serum bilirubin </= 1.5 x upper limit of normal. - SGOT and SGPT /=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 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 /= 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.
|Contacts and Locations|
|United States, Ohio||The Ohio State University Cancer Center||Columbus|
|Sponsors and Collaborators|
|Ohio State University Comprehensive Cancer Center|
|Principal Investigator :||Jonathan Brammer, MD||The Ohio State University Comprehensive Cancer Center|
|Responsible Party :||Ohio State University Comprehensive Cancer Center|
|ClinicalTrials.gov Identifier :||NCT02512497|
|Other Study ID Numbers :||OSU-16242, NCI-2015-01555|
|First Posted :||July 31, 2015|
|Last Update Posted :||January 7, 2020|
|Last Verified :||January 2020|
Data (IPD) Sharing
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
|Keywords provided by Ohio State University Comprehensive Cancer Center:||
Cutaneous T-cell Lymphoma
T-Large Granulocytic Leukemia
Peripheral T-Cell Lymphoma PTCL
Allogeneic stem cell transplantation
|Additional relevant MeSH terms :||