Study Stopped
Closed due to very slow accrual
Lenalidomide Combined With Vorinostat/Gemcitabine/Busulfan/Melphalan With Autologous Stem-Cell Transplantation in Diffuse Large B-Cell Lymphoma of the ABC Subtype
2 other identifiers
interventional
8
1 country
1
Brief Summary
The goal of this clinical research study is to find the highest tolerable dose of lenalidomide that can be given in combination with vorinostat, gemcitabine, busulfan, and melphalan, with a stem cell transplant, and with or without rituximab. Researchers also want to learn about the safety and effectiveness of this combination.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1 lymphoma
Started Jun 2016
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 26, 2015
CompletedFirst Posted
Study publicly available on registry
October 28, 2015
CompletedStudy Start
First participant enrolled
June 22, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 8, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
April 8, 2019
CompletedResults Posted
Study results publicly available
December 13, 2019
CompletedDecember 13, 2019
November 1, 2019
2.8 years
October 26, 2015
November 6, 2019
November 26, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Maximum Tolerated Dose (MTD)
Established the maximum tolerated dose (MTD) of lenalidomide combined with vorinostat/gemcitabine/busulfan/melphalan with autologous stem-cell transplant ASCT). Maximum tolerated dose (MTD) of lenalidomide based on DLT was defined as any Grade 4 or 5 nonhematologic, noninfectious toxicity or any grade 3 mucositis or skin toxicity lasting \> 5 days at their peak severity. Lenalidomide doses were chosen adaptively for successive cohorts with a minimum size of 2 patients. Toxicity scoring followed the National Cancer Institute Common Toxicity Criteria, version 4.
Enrollment up to day 30 post transplant for each dosing cohort
Event-free Survival (EFS)
Determined the 2-year event-free survival (EFS)
Up to 2 years post transplant
Secondary Outcomes (5)
Overall Survival (OS)
Up to 2 years post transplant
Complete Remission (CR) Rate
Up to 2 years post transplant
Overall Remission Rate (ORR)
Up to 2 years post transplant
Toxicity Profile
Up to 2 years post transplant
Pharmacodynamic Studies
Up to 2 years post transplant
Study Arms (1)
Lenalidomide + Vorinostat/Gem/Bu/Mel + AutoSCT
EXPERIMENTALVorinostat and lenalidomide administered orally at the same time within 1 hour before the daily dose of chemotherapy. Gemcitabine administered as a loading dose of 75 mg/m2 followed by infusion on days -8 and -3. Busulfan test dose administered as outpatient before admission, or as inpatient on day -10. The "test dose" of 32 mg/m2 based on actual body weight. Doses of days -6 and -5 subsequently adjusted to target an AUC of 4,000 microMol.min-1. Melphalan administered at 60 mg/m2 on days -3 and -2. Patients with CD20+ tumors receive rituximab 375 mg/m2 on day -9 in the AM as an inpatient. Dexamethasone 8 mg by vein twice a day from day -8 to day -2. Caphosol oral rinses 30 mL four times a day used from day -8. Oral glutamine, 15 g four times a day, swished, gargled and swallowed started on day -8. Pyridoxine 100 mg by vein or mouth three times a day from day -1. Enoxaparin 40 mg subcutaneously daily from admission until platelet count drops below 50,000/mm3.
Interventions
Dose Escalation Phase Starting dose of Lenalidomide: 50 mg by mouth on Days -9 to -2. Dose Expansion Phase Starting Dose: Maximum tolerated dose from Phase I.
1000 mg by mouth on Days -9 to -2.
Gemcitabine administered as a loading dose of 75 mg/m2 by vein on Day -8 and 2775 mg by vein on Day -3.
Busulfan test dose administered by vein either as outpatient before admission, or as inpatient on day -10. The "test dose" of 32 mg/m2 based on actual body weight. Doses of days -6 and -5 subsequently adjusted to target an AUC of 4,000 microMol.min-1.
60 mg/m2 by vein on days -3 and -2.
Patients with CD20+ tumors receive Rituximab 375 mg/m2 by vein on day -9 in the AM as an inpatient.
8 mg by vein twice a day from Day -8 AM to Day -2 PM.
Caphosol oral rinses 30 mL four times a day used from Day -8.
Oral glutamine, 15 g four times a day, swished, gargled and swallowed started on Day -8.
100 mg by vein or mouth three times a day from Day -1
40 mg subcutaneously daily from admission until platelet count drops below 50,000/mm3.
Stem cell transplant performed on Day 0.
Palifermin per departmental standard of care with 3 doses to be administered prior to starting chemotherapy and 3 doses starting on day 0.
Eligibility Criteria
You may qualify if:
- Age 15-65
- Patients with ABC (determined by immunohistochemistry using the Hans algorithmI) DLBCL with primary refractory disease, relapse \<12 months after initial therapy, secondary International Prognostic Index (IPI) \>1, less than partial response to salvage treatment or exposure to \>3 salvage regimens
- Adequate renal function, as defined by an estimated serum creatinine clearance \>/= 50 ml/min (MDRD method) and/or serum creatinine \</= 1.8 mg/dL
- Adequate hepatic function (SGOT and/or SGPT \</= 3 x ULN; bilirubin and ALP \</= 2 x ULN
- Adequate pulmonary function with FEV1, FVC and DLCO (corrected for Hgb) \>/= 50%
- Adequate cardiac function with left ventricular ejection fraction \>/= 40%. No uncontrolled arrhythmias or symptomatic cardiac disease
- ECOG performance status \<2
- Negative Beta HCG in woman with child-bearing potential
- All study participants must be registered into the mandatory Revlimid REMS program, and be willing and able to comply with the requirements of the REMS program.
- Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS program.
You may not qualify if:
- Grade \>/= 3 non-hematologic toxicity from previous therapy that has not resolved to \</= G1
- Prior whole brain irradiation
- 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
- Active infection requiring parenteral antibiotics
- HIV infection, unless receiving effective antiretroviral therapy with undetectable viral load and normal CD4 counts
- Radiation therapy in the month prior to enrollment
- History of arterial thromboembolic events in the past 3 months and of venous thromboembolic events in the past month
- History of hypersensitivity of lenalidomide or thalidomide
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- M.D. Anderson Cancer Centerlead
- Celgene Corporationcollaborator
Study Sites (1)
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Yago Nieto/Professor, Stem Cell Transplantation
- Organization
- UT MD Anderson Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Yago Nieto, MD, PHD
M.D. Anderson Cancer Center
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 26, 2015
First Posted
October 28, 2015
Study Start
June 22, 2016
Primary Completion
April 8, 2019
Study Completion
April 8, 2019
Last Updated
December 13, 2019
Results First Posted
December 13, 2019
Record last verified: 2019-11