Lenalidomide Combined With Vorinostat/Gemcitabine/Busulfan/Melphalan With Autologous Stem-Cell Transplantation in Diffuse Large B-Cell Lymphoma of the ABC Subtype
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|ClinicalTrials.gov Identifier: NCT02589145|
Recruitment Status : Active, not recruiting
First Posted : October 28, 2015
Last Update Posted : May 23, 2018
|Condition or disease||Intervention/treatment||Phase|
|Lymphoma||Drug: Lenalidomide Drug: Vorinostat Drug: Gemcitabine Drug: Busulfan Drug: Melphalan Drug: Rituximab Drug: Dexamethasone Drug: Caphosol Drug: Glutamine Drug: Pyridoxine Drug: Enoxaparin Procedure: Stem Cell Transplant Drug: Palifermin||Phase 1 Phase 2|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||8 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Lenalidomide Combined With Vorinostat/Gemcitabine/Busulfan/Melphalan With Autologous Stem-Cell Transplantation in Diffuse Large B-Cell Lymphoma of the ABC Subtype|
|Actual Study Start Date :||June 22, 2016|
|Estimated Primary Completion Date :||June 2021|
|Estimated Study Completion Date :||June 2021|
Experimental: Lenalidomide + Vorinostat/Gem/Bu/Mel + AutoSCT
Vorinostat 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.
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.
Other Name: Alkeran
Patients with CD20+ tumors receive Rituximab 375 mg/m2 by vein on day -9 in the AM as an inpatient.
Other Name: Rituxan
8 mg by vein twice a day from Day -8 AM to Day -2 PM.
Other Name: Decadron
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.
Other Name: Lovenox Injection
Procedure: Stem Cell Transplant
Stem cell transplant performed on Day 0.
Other Name: SCT
Palifermin per departmental standard of care with 3 doses to be administered prior to starting chemotherapy and 3 doses starting on day 0.
Other Name: Kepivance
- Maximum Tolerated Dose (MTD) of Lenalidomide with Vorinostat, Gemcitabine, Busulfan, Melphalan and Autologous Stem-Cell Transplant z(ASCT) [ Time Frame: 2 weeks ]
MTD defined as the highest dose for which the posterior probability of toxicity is closest to 35%, among all the tried doses i for which Pr (di > 0.35 | data) < 0.95.
Dose limiting toxicity defined as any grade 4 or 5 non-hematological, non-infectious toxicity attributable to Lenalidomide/Vorinostat/GemBuMel, as well as grade 3 mucositis and grade 3 skin toxicity lasting for more than 5 days at their peak severity.
- Event Free Survival of Lenalidomide with Vorinostat, Gemcitabine, Busulfan, Melphalan and Autologous Stem-Cell Transplant (ASCT) [ Time Frame: 2 years ]
Assuming the 2-year EFS for standard treatment is 30% (historical control), the accrual rate is 1 year with a 2 year follow-up, a sample size of 20 patients would achieve 81% power to detect a difference of 25% in EFS (55% for experimental treatment) using a one-sided significance level of 5% (SWOG statistical tools for one arm survival).
EFS estimated using the Kaplan-Meier method.
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): NCT02589145
|United States, Texas|
|University of Texas MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Yago Nieto, MD, PHD||M.D. Anderson Cancer Center|