Belinostat Combined With Azacitidine/Gemcitabine/Busulfan/Melphalan With Autologous Stem-Cell Transplantation in Refractory or Relapsed Lymphoma

NCT02701673 | Withdrawn Phase 1

• 1 other identifier: 2015-0560
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical research study is to find the highest tolerable dose of belinostat that can be given in combination with azacitidine, gemcitabine, busulfan, and melphalan to patients who are scheduled to have a stem cell transplant. If you have diffuse large B-cell lymphoma (DLBCL), you will also receive rituximab. Researchers also want to learn about the safety and effectiveness of this combination.

Conditions

Lymphoma

Keywords

Refractory or Relapsed Lymphoma; Busulfan; Busulfex; Myleran; Caphosol; Glutamine; Enterex; Glutapak-10; NutreStore; Resource; GlutaSolve; Sympt-X-G.I.; Sympt-X; Pyridoxine; Belinostat; Azacitidine; 5-azacytidine; 5-aza; Azacytidine; Vidaza; 5-AZC; AZA-CR; Ladakamycin; Gemcitabine; Gemcitabine Hydrochloride; Gemzar; Stem cell transplant; SCT; Melphalan; Alkeran

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Belinostat Combined with Azacitidine and Gemcitabine/Busulfan/Melphalan (AZA-GemBuMel) in Participants with Refractory or Poor-Risk Relapsed Lymphoma

  For purpose of dose-finding, "toxicity" defined as any of the following events occurring within 30 days from the start of Belinostat infusion : 1. any grade 4 or 5 non-hematologic toxicity, or 2. any grade 3 or 4 mucositis, or 3. any grade 3 or 4 skin toxicity lasting \> 5 days at peak severity Optimal dose defined as that for which the posterior mean of Pr(toxicity within 30 days \| dose) given the current data is closest to 0.30.

  30 days

Secondary Outcomes (1)

• Treatment Related Mortality (TRM100)

  100 days after stem cell transplant

Study Arms (1)

Belinostat/Gem/Bu/Mel + AutoSCT

EXPERIMENTAL

Busulfan "test dose" administered by vein on Day -10. Test dose of 32 mg/m2 based on actual body weight. Busulfan pharmacokinetics performed with the test dose and the first dose on Day -8. Doses on Days -6 and -5 subsequently adjusted to target an area under curve (AUC) of 4,000 microMol.min-1. Caphosol oral rinses 30 mL four times a day used from Day -8. Oral Glutamine, 15 g swished, gargled and swallowed four times a day starting on Day -8. Pyridoxine 100 mg by vein or mouth three times a day staring on Day -1. Starting dose of Belinostat 100 mg/ m2/day by vein on Day -9 through Day -2. Azacitidine 15 mg/m2/day by vein on Day -9 through Day -2. Participants with cluster of differentiation antigen 20 (CD20+) tumors receive Rituximab 375 mg/m2 by vein on Day -9. Gemcitabine 75 mg/m2 by vein administered as a loading dose followed by prolonged infusion on Days -8 and -3. Melphalan 60 mg/m2/d by vein on Day -2. Stem cell transplant by vein given on Day 0.

Drug: Busulfan; Drug: Caphosol; Drug: Glutamine; Drug: Pyridoxine; Drug: Belinostat; Drug: Azacitidine; Drug: Gemcitabine; Drug: Melphalan; Procedure: Stem Cell Transplant

Interventions

Busulfan DRUG

Busulfan "test dose" administered by vein on Day -10. Test dose of 32 mg/m2 based on actual body weight. Busulfan pharmacokinetics performed with the test dose and the first dose on Day -8. Doses on Days -6 and -5 subsequently adjusted to target an AUC of 4,000 microMol.min-1.

Also known as: Busulfex, Myleran

Belinostat/Gem/Bu/Mel + AutoSCT

Caphosol DRUG

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

Belinostat/Gem/Bu/Mel + AutoSCT

Glutamine DRUG

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

Also known as: Enterex, Glutapak-10, NutreStore, Resource, GlutaSolve, Sympt-X G.I., Sympt-X

Belinostat/Gem/Bu/Mel + AutoSCT

Pyridoxine DRUG

Pyridoxine 100 mg by vein or mouth three times a day staring on Day -1

Belinostat/Gem/Bu/Mel + AutoSCT

Belinostat DRUG

Starting dose of Belinostat 100 mg/ m2/day by vein on Day -9 through Day -2.

Belinostat/Gem/Bu/Mel + AutoSCT

Azacitidine DRUG

Azacitidine 15 mg/m2/day by vein on Day -9 through Day -2.

Belinostat/Gem/Bu/Mel + AutoSCT

Gemcitabine DRUG

Gemcitabine 75 mg/m2 by vein administered as a loading dose followed by prolonged infusion on Days -8 and -3.

Belinostat/Gem/Bu/Mel + AutoSCT

Melphalan DRUG

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

Also known as: Alkeran

Belinostat/Gem/Bu/Mel + AutoSCT

Stem Cell Transplant PROCEDURE

Stem cell transplant performed on Day 0.

Belinostat/Gem/Bu/Mel + AutoSCT

Eligibility Criteria

• Age: 15 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 15-65
• Patients with: 2. 1. DLBCL with one of the following: 2.1.1. Primary refractory (no CR to 1st line). 2.1.2. High-risk relapse (CR1 \<6 months, secondary IPI \>1, high LDH). 2.1.3. Refractory relapse: No response (SD or PD) to \>/= 1 line of salvage. 2.2. Hodgkin's with one of the following: 2.2.1. Primary refractory (no CR to 1st line or PD within 3 months). 2.2.2. High-risk relapse (CR1 \<1 year, extranodal relapse, B symptoms). 2.2.3. Refractory relapse: No response (SD or PD) to \>/= 1 line of salvage. 2.3. T-NHL with one of the following: 2.3.1. Primary refractory (\</= CR to 1st line or relapse within 6 months). 2.3.2. Nonresponsive (SD/PD) to \>/= 1 line of salvage. 2.4. Burkitt's or lymphoblastic lymphoma with one of the following: 2.4.1. Primary refractory (\</= CR to 1st line or relapse within 6 months). 2.4.2. Refractory to at least 1 line of salvage (SD/PD).
• Adequate renal function, as defined by estimated serum creatinine clearance \>/= 50 ml/min and/or serum creatinine \</= 1.8 mg/dL.
• Adequate hepatic function (SGOT and/or serum glutamate pyruvate transaminase (SGPT) \</= 3 x upper limit of normal (ULN); bilirubin and ALP \</= 2 x ULN.
• Adequate pulmonary function with forced expiratory volume at one second (FEV1), forced vital capacity (FVC) and diffusing capacity of lung for carbon monoxide (DLCO) (corrected for Hgb) \>/= 50%.
• Adequate cardiac function with left ventricular ejection fraction \>/= 40%. No uncontrolled arrhythmias or symptomatic cardiac disease.
• PS \<2.
• Negative Beta human chorionic gonadotropin (HCG) in woman with child-bearing potential.

You may not qualify if:

• Grade \>/= 3 non-hematologic toxicity from previous therapy that has not resolved to \</= G1.
• Prior whole brain irradiation.
• Corrected QT interval (QTc) longer than 500 ms.
• 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 cluster of differentiation 4 (CD4) counts.
• Radiation therapy in the month prior to enrollment.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Lymphoma

Interventions

Busulfan; Glutamine; Health Resources; Pyridoxine; belinostat; Azacitidine; Gemcitabine; Melphalan; Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Neutral; Health Planning; Health Care Economics and Organizations; Delivery of Health Care; Health Care Quality, Access, and Evaluation; Vitamin B 6; Picolines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Aza Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Deoxycytidine; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Yago Nieto, MD, PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

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: March 2, 2016
• First Posted: March 8, 2016
• Study Start: June 1, 2016
• Primary Completion: June 1, 2019
• Last Updated: May 4, 2016

Record last verified: 2016-05