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Trial record 90 of 230 for:    pyridoxine

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

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ClinicalTrials.gov Identifier: NCT02701673
Recruitment Status : Withdrawn
First Posted : March 8, 2016
Last Update Posted : May 4, 2016
Sponsor:
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 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.

Condition or disease Intervention/treatment Phase
Lymphoma Drug: Busulfan Drug: Caphosol Drug: Glutamine Drug: Pyridoxine Drug: Belinostat Drug: Azacitidine Drug: Gemcitabine Drug: Melphalan Procedure: Stem Cell Transplant Phase 1 Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Belinostat Combined With Azacitidine/Gemcitabine/Busulfan/Melphalan With Autologous Stem-Cell Transplantation in Refractory or Relapsed Lymphoma
Study Start Date : June 2016
Estimated Primary Completion Date : June 2019


Arm Intervention/treatment
Experimental: Belinostat/Gem/Bu/Mel + AutoSCT

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
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.
Other Names:
  • Busulfex
  • Myleran

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

Drug: Glutamine
Oral Glutamine, 15 g swished, gargled and swallowed four times a day starting on Day -8.
Other Names:
  • Enterex
  • Glutapak-10
  • NutreStore
  • Resource
  • GlutaSolve
  • Sympt-X G.I.
  • Sympt-X

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

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

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

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

Drug: Melphalan
Melphalan 60 mg/m2 by vein on Days -3 and -2.
Other Name: Alkeran

Procedure: Stem Cell Transplant
Stem cell transplant performed on Day 0.




Primary Outcome Measures :
  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 [ Time Frame: 30 days ]

    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.



Secondary Outcome Measures :
  1. Treatment Related Mortality (TRM100) [ Time Frame: 100 days after stem cell transplant ]
    Treatment related mortality (TRM100), defined as death due to any cause without disease recurrence within 100 days post stem cell transplant (SCT).



Information from the National Library of Medicine

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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: 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).
  3. Adequate renal function, as defined by estimated serum creatinine clearance >/= 50 ml/min and/or serum creatinine </= 1.8 mg/dL.
  4. Adequate hepatic function (SGOT and/or serum glutamate pyruvate transaminase (SGPT) </= 3 x upper limit of normal (ULN); bilirubin and ALP </= 2 x ULN.
  5. 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%.
  6. Adequate cardiac function with left ventricular ejection fraction >/= 40%. No uncontrolled arrhythmias or symptomatic cardiac disease.
  7. PS <2.
  8. Negative Beta human chorionic gonadotropin (HCG) in woman with child-bearing potential.

Exclusion Criteria:

  1. Grade >/= 3 non-hematologic toxicity from previous therapy that has not resolved to </= G1.
  2. Prior whole brain irradiation.
  3. Corrected QT interval (QTc) longer than 500 ms.
  4. Active hepatitis B, either active carrier (HBsAg +) or viremic (HBV DNA >/= 10,000 copies/mL, or >/= 2,000 IU/mL).
  5. Evidence of either cirrhosis or stage 3-4 liver fibrosis in patients with chronic hepatitis C or positive hepatitis C serology.
  6. Active infection requiring parenteral antibiotics.
  7. HIV infection, unless receiving effective antiretroviral therapy with undetectable viral load and normal cluster of differentiation 4 (CD4) counts.
  8. Radiation therapy in the month prior to enrollment.

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): NCT02701673


Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
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Principal Investigator: Yago Nieto, MD, PHD M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02701673     History of Changes
Other Study ID Numbers: 2015-0560
First Posted: March 8, 2016    Key Record Dates
Last Update Posted: May 4, 2016
Last Verified: May 2016
Keywords provided by M.D. Anderson Cancer Center:
Pyridoxine
Refractory or Relapsed Lymphoma
Busulfan
Busulfex
Myleran
Caphosol
Glutamine
Enterex
Glutapak-10
NutreStore
Resource
GlutaSolve
Sympt-X-G.I.
Sympt-X
Belinostat
Azacitidine
5-azacytidine
5-aza
Azacytidine
Vidaza
5-AZC
AZA-CR
Ladakamycin
Gemcitabine
Gemcitabine Hydrochloride
Gemzar
Stem cell transplant
SCT
Melphalan
Alkeran
Additional relevant MeSH terms:
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Pyridoxine
Pyridoxal
Vitamin B 6
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Gemcitabine
Azacitidine
Melphalan
Busulfan
Belinostat
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Vitamin B Complex
Vitamins