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 |
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Recruitment Status :
Terminated
(Closed due to very slow accrual)
First Posted : October 28, 2015
Last Update Posted : May 29, 2019
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| 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 |
| Actual Primary Completion Date : | April 8, 2019 |
| Actual Study Completion Date : | April 8, 2019 |
| Arm | Intervention/treatment |
|---|---|
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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:
Drug: Vorinostat 1000 mg by mouth on Days -9 to -2.
Other Names:
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:
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:
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:
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 |
- 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.
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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 |
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
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 |
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 29, 2019 |
| Last Verified: | May 2019 |
| 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:
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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:
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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 Dexamethasone acetate Gemcitabine Rituximab Lenalidomide |
Melphalan Busulfan Vorinostat BB 1101 Pyridoxine Pyridoxal Vitamin B 6 Enoxaparin Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Glucocorticoids |