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

Sponsor:

Collaborator:

Celgene Corporation

Information provided by (Responsible Party):

M.D. Anderson Cancer Center

Study Description

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.

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 Design


Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	8 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Drug Information available for: Busulfan Melphalan Melphalan hydrochloride Gemcitabine Gemcitabine hydrochloride Vorinostat Lenalidomide

Genetic and Rare Diseases Information Center resources: Lymphosarcoma B-cell Lymphoma Diffuse Large B-Cell Lymphoma

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
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.	Drug: Lenalidomide 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. Other Names: CC-5013 Revlimid Drug: Vorinostat 1000 mg by mouth on Days -9 to -2. Other Names: SAHA Suberoylanilide Hydroxamic Acid MSK-390 Zolinza Drug: Gemcitabine Gemcitabine administered as a loading dose of 75 mg/m2 by vein on Day -8 and 2775 mg by vein on Day -3. Other Names: Gemcitabine Hydrochloride Gemzar Drug: Busulfan 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. Other Names: Busulfex Myleran Drug: Melphalan 60 mg/m2 by vein on days -3 and -2. Other Name: Alkeran Drug: Rituximab Patients with CD20+ tumors receive Rituximab 375 mg/m2 by vein on day -9 in the AM as an inpatient. Other Name: Rituxan Drug: Dexamethasone 8 mg by vein twice a day from Day -8 AM to Day -2 PM. Other Name: Decadron Drug: Caphosol Caphosol oral rinses 30 mL four times a day used from Day -8. Drug: Glutamine Oral glutamine, 15 g four times a day, swished, gargled and swallowed started on Day -8. Other Names: Enterex Glutapak-10 NutreStore Resource GlutaSolve Sympt-X G.I. Symptx-X Drug: Pyridoxine 100 mg by vein or mouth three times a day from Day -1 Drug: Enoxaparin 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 Drug: Palifermin 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

Arm

Intervention/treatment

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.

Drug: Lenalidomide

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.

Other Names:

CC-5013
Revlimid

Drug: Vorinostat

1000 mg by mouth on Days -9 to -2.

Other Names:

SAHA
Suberoylanilide Hydroxamic Acid
MSK-390
Zolinza

Drug: Gemcitabine

Gemcitabine administered as a loading dose of 75 mg/m2 by vein on Day -8 and 2775 mg by vein on Day -3.

Other Names:

Gemcitabine Hydrochloride
Gemzar

Drug: Busulfan

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.

Other Names:

Busulfex
Myleran

Drug: Melphalan

60 mg/m2 by vein on days -3 and -2.

Other Name: Alkeran

Drug: Rituximab

Patients with CD20+ tumors receive Rituximab 375 mg/m2 by vein on day -9 in the AM as an inpatient.

Other Name: Rituxan

Drug: Dexamethasone

8 mg by vein twice a day from Day -8 AM to Day -2 PM.

Other Name: Decadron

Drug: Caphosol

Caphosol oral rinses 30 mL four times a day used from Day -8.

Drug: Glutamine

Oral glutamine, 15 g four times a day, swished, gargled and swallowed started on Day -8.

Other Names:

Enterex
Glutapak-10
NutreStore
Resource
GlutaSolve
Sympt-X G.I.
Symptx-X

Drug: Pyridoxine

100 mg by vein or mouth three times a day from Day -1

Drug: Enoxaparin

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

Drug: Palifermin

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

Outcome Measures

Primary Outcome Measures :

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.

Secondary Outcome Measures :

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.

Eligibility Criteria

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Ages Eligible for Study:	15 Years to 65 Years (Child, Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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

Contacts and Locations

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): NCT02589145

Locations


United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

Celgene Corporation

Investigators


Principal Investigator:	Yago Nieto, MD, PHD	M.D. Anderson Cancer Center

More Information

Additional Information:

University of Texas MD Anderson Cancer Center Website This link exits the ClinicalTrials.gov site


Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT02589145 History of Changes
Other Study ID Numbers:	2015-0558 NCI-2015-01938 ( Registry Identifier: NCI CTRP )
First Posted:	October 28, 2015 Key Record Dates
Last Update Posted:	May 23, 2018
Last Verified:	May 2018


Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by M.D. Anderson Cancer Center:


Blood And Marrow Transplantation Diffuse large B-cell lymphoma DLBCL Busulfan Busulfex Myleran Lenalidomide CC-5013 Revlimid Vorinostat SAHA Suberoylanilide Hydroxamic Acid MSK-390 Zolinza Gemcitabine	Gemcitabine Hydrochloride Gemzar Melphalan Alkeran Rituximab Rituxan Dexamethasone Decadron Glutamine Enterex Glutapack-10 NutreStore Resource GlutaSolve Sympt-X G.I.

Additional relevant MeSH terms:


Lymphoma Lymphoma, B-Cell Lymphoma, Large B-Cell, Diffuse Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Lymphoma, Non-Hodgkin Dexamethasone acetate Dexamethasone Gemcitabine Lenalidomide Vorinostat	Rituximab Thalidomide Melphalan Busulfan BB 1101 Pyridoxine Pyridoxal Vitamin B 6 Enoxaparin Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents

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