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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

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 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


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




Primary Outcome Measures :
  1. 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 :
  1. 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.




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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:

  1. Age 15-65
  2. 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
  3. Adequate renal function, as defined by an estimated serum creatinine clearance >/= 50 ml/min (MDRD method) and/or serum creatinine </= 1.8 mg/dL
  4. Adequate hepatic function (SGOT and/or SGPT </= 3 x ULN; bilirubin and ALP </= 2 x ULN
  5. Adequate pulmonary function with FEV1, FVC and DLCO (corrected for Hgb) >/= 50%
  6. Adequate cardiac function with left ventricular ejection fraction >/= 40%. No uncontrolled arrhythmias or symptomatic cardiac disease
  7. ECOG performance status <2
  8. Negative Beta HCG in woman with child-bearing potential
  9. 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.
  10. Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS program.

Exclusion Criteria:

  1. Grade >/= 3 non-hematologic toxicity from previous therapy that has not resolved to </= G1
  2. Prior whole brain irradiation
  3. Active hepatitis B, either active carrier (HBsAg +) or viremic (HBV DNA >/= 10,000 copies/mL, or >/= 2,000 IU/mL)
  4. Evidence of either cirrhosis or stage 3-4 liver fibrosis in patients with chronic hepatitis C or positive hepatitis C serology
  5. Active infection requiring parenteral antibiotics
  6. HIV infection, unless receiving effective antiretroviral therapy with undetectable viral load and normal CD4 counts
  7. Radiation therapy in the month prior to enrollment
  8. History of arterial thromboembolic events in the past 3 months and of venous thromboembolic events in the past month
  9. History of hypersensitivity of lenalidomide or thalidomide

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

Additional Information:
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