Clinical Trial: NCT04220008 - My Cancer Genome

NCT04220008

Description:

This phase II trial studies how well vorinostat and combination chemotherapy before donor stem cell transplantation work in treating patients with aggressive B-cell or T-cell non-Hodgkin lymphoma that has come back (relapsed). Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as busulfan, gemcitabine, and clofarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving vorinostat together with combination chemotherapy before donor stem cell transplantation may help to control lymphoma.

Related Conditions:

B-Cell Non-Hodgkin Lymphoma
Burkitt Lymphoma
Diffuse Large B-Cell Lymphoma
Non-Hodgkin Lymphoma
T-Cell Non-Hodgkin Lymphoma
Transformed Non-Hodgkin Lymphoma

Recruiting Status:

Not yet recruiting

Phase:

Phase 2

URL:

https://clinicaltrials.gov/show/NCT04220008

Trial Eligibility

Document

Title

Brief Title: Vorinostat and Combination Chemotherapy Before Donor Stem Cell Transplantation for the Treatment of Relapsed Aggressive B-cell or T-cell Non-Hodgkin Lymphoma
Official Title: Vorinostat With Gemcitabine/Clofarabine/Busulfan for Allogeneic Transplantation for Aggressive Lymphomas

Clinical Trial IDs

ORG STUDY ID: 2018-0988
SECONDARY ID: NCI-2019-08496
SECONDARY ID: 2018-0988
SECONDARY ID: P30CA016672
NCT ID: NCT04220008

Conditions

Recurrent Aggressive Non-Hodgkin Lymphoma
Recurrent B-Cell Non-Hodgkin Lymphoma
Recurrent Burkitt Lymphoma
Recurrent Diffuse Large B-Cell Lymphoma
Recurrent High Grade B-Cell Lymphoma
Recurrent T-Cell Non-Hodgkin Lymphoma
Recurrent Transformed B-Cell Non-Hodgkin Lymphoma

Interventions

Drug	Synonyms	Arms
Busulfan	1, 4-Bis[methanesulfonoxy]butane, BUS, Bussulfam, Busulfanum, Busulfex, Busulphan, CB 2041, CB-2041, Glyzophrol, GT 41, GT-41, Joacamine, Methanesulfonic Acid Tetramethylene Ester, Methanesulfonic acid, tetramethylene ester, Mielucin, Misulban, Misulfan, Mitosan, Myeleukon, Myeloleukon, Myelosan, Mylecytan, Myleran, Sulfabutin, Tetramethylene Bis(methanesulfonate), Tetramethylene bis[methanesulfonate], WR-19508	Treatment (busulfan, vorinostat, gemcitabine, clofarabine)
Clofarabine	Clofarex, Clolar	Treatment (busulfan, vorinostat, gemcitabine, clofarabine)
Cyclophosphamide	(-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719	Treatment (busulfan, vorinostat, gemcitabine, clofarabine)
Gemcitabine	dFdC, dFdCyd, Difluorodeoxycytidine	Treatment (busulfan, vorinostat, gemcitabine, clofarabine)
Mycophenolate Mofetil	Cellcept, MMF	Treatment (busulfan, vorinostat, gemcitabine, clofarabine)
Rituximab	ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, Rituximab ABBS, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar JHL1101, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, rituximab biosimilar TQB2303, rituximab-abbs, RTXM83, Truxima	Treatment (busulfan, vorinostat, gemcitabine, clofarabine)
Tacrolimus	FK 506, Fujimycin, Hecoria, Prograf, Protopic	Treatment (busulfan, vorinostat, gemcitabine, clofarabine)
Vorinostat	L-001079038, MSK-390, SAHA, Suberanilohydroxamic Acid, Suberoylanilide Hydroxamic Acid, Zolinza	Treatment (busulfan, vorinostat, gemcitabine, clofarabine)

Purpose

Detailed Description

      PRIMARY OBJECTIVE:

      I. Estimate the progression-free survival (PFS) time.

      SECONDARY OBJECTIVES:

      I. Estimate the day 100 non-relapse mortality (NRM) of allogeneic stem cell transplantation
      (allo SCT) using vorinostat/gemcitabine/clofarabine/busulfan (SAHA/Gem/Clo/Bu) with
      post-transplant cyclophosphamide (PT-CY).

      II. Estimate the graft versus host disease (GVHD)-free/relapse free survival (GRFS) in
      patients with refractory lymphoma receiving an allo SCT with SAHA/Gem/Clo/Bu with PT-CY.

      III. Estimate the overall survival (OS) in patients with refractory lymphoma receiving an
      allo SCT with SAHA/Gem/Clo/Bu with PT-CY.

      IV. Assess the 1-year NRM in patients with refractory lymphoma receiving an allo SCT with
      SAHA/Gem/Clo/Bu with PT-CY.

      V. Assess the relapse rate in patients with refractory lymphoma receiving an allo SCT with
      SAHA/Gem/Clo/Bu with PT-CY.

      VI. Assess the graft failure rate in patients with refractory lymphoma receiving an allo SCT
      with SAHA/Gem/Clo/Bu with PT-CY.

      VII. Assess the time to neutrophil and platelet engraftment in patients with refractory
      lymphoma receiving an allo SCT with SAHA/Gem/Clo/Bu with PT-CY.

      VIII. Assess the incidence of grade 2-4 and grade 3-4 acute graft versus host disease (GVHD)
      in patients with refractory lymphoma receiving an allo SCT with SAHA/Gem/Clo/Bu with PT-CY.

      IX. Assess the overall and severe chronic GVHD in patients with refractory lymphoma receiving
      an allo SCT with SAHA/Gem/Clo/Bu with PT-CY.

      X. Determine the incidence of grade 3 and 4 nonhematological adverse events in patients with
      refractory lymphoma receiving an allo SCT with SAHA/Gem/Clo/Bu with PT-CY.

      TERTIARY OBJECTIVE:

      I. Describe changes of deoxyribonucleic acid (DNA) damage response and repair, poly
      (ADP-ribose) polymerase (PARP) inhibition and downstream cellular effects in peripheral blood
      mononuclear cells (PBMNC), and, when available, malignant lymphocytes obtained by fine needle
      aspiration (FNA) of peripheral lymph nodes of patients with refractory lymphoma receiving an
      allo SCT with SAHA/Gem/Clo/Bu with PT-CY.

      OUTLINE:

      Patients receive a low-level "test" dose of busulfan intravenously (IV) over up to 1 hour on
      days -15 to -9, vorinostat orally (PO) once daily (QD) on days -8 to -4, gemcitabine IV over
      about 90 minutes on days -7 and -5, clofarabine IV over about 1 hour and high-dose busulfan
      IV over 3 hours on days -7 to -4. Patients with CD20 positive (+) lymphoma also receive
      rituximab IV over 3 to 6 hours on days -15, -8, 1, and 8. Patients undergo allogeneic
      hematopoietic stem cell transplantation (HSCT) on day 0. Patients then receive
      cyclophosphamide IV over 2 hours on days 3 and 4. Beginning day 5, patients receive standard
      of care tacrolimus IV over 24 hours and mycophenolate mofetil IV over 2 hours three times
      daily (TID) until they can be tolerated PO. Once tolerated PO, patients receive tacrolimus PO
      twice daily (BID) for 6 months and mycophenolate mofetil PO TID for up to 30 days in the
      absence of disease progression or unacceptable toxicity. After 30 days, patients who develop
      GVHD continue treatment with mycophenolate mofetil at physician's discretion.

      After completion of study treatment, patients are followed up at 3, 6, and 12 months after
      stem cell transplant, then every 6 months for 4 years.

Trial Arms

Name	Type	Description	Interventions
Treatment (busulfan, vorinostat, gemcitabine, clofarabine)	Experimental	Patients receive a low-level "test" dose of busulfan IV over up to 1 hour on days -15 to -9, vorinostat PO QD on days -8 to -4, gemcitabine IV over about 90 minutes on days -7 and -5, clofarabine IV over about 1 hour and high-dose busulfan IV over 3 hours on days -7 to -4. Patients with CD20 positive (+) lymphoma also receive rituximab IV over 3 to 6 hours on days -15, -8, 1, and 8. Patients undergo HSCT on day 0. Patients then receive cyclophosphamide IV over 2 hours on days 3 and 4. Beginning day 5, patients receive standard of care tacrolimus IV over 24 hours and mycophenolate mofetil IV over 2 hours TID until they can be tolerated PO. Once tolerated PO, patients receive tacrolimus PO BID for 6 months and mycophenolate mofetil PO TID for up to 30 days in the absence of disease progression or unacceptable toxicity. After 30 days, patients who develop GVHD continue treatment with mycophenolate mofetil at physician's discretion	Busulfan Clofarabine Cyclophosphamide Gemcitabine Mycophenolate Mofetil Rituximab Tacrolimus Vorinostat

Eligibility Criteria

        Inclusion Criteria:

          -  Relapsed aggressive B-cell non-Hodgkin lymphoma (B-NHL) (diffuse large B-cell lymphoma
             [DLBCL], transformed B-NHL, high-grade B-cell lymphoma [HGBL] or Burkitt) or T-cell
             non-Hodgkin lymphoma (T-NHL) who meet both of the following criteria: a. High or very
             high disease risk index (DRI), and b. No response to at least 1 line of salvage
             chemotherapy, or relapse after a prior autologous SCT

          -  An 8/8 human leukocyte antigen (HLA) matched (high resolution typing at A, B, C, DRB1)
             sibling or unrelated donor, or a haploidentical donor

          -  Left ventricular ejection fraction (EF) >= 45%

          -  Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and corrected
             diffusion capacity of the lung for carbon monoxide (DLCO) >= 50%

          -  Estimated serum creatinine clearance >= 50 ml/min (using the Cockcroft-Gault formula)

          -  Serum bilirubin =< 2 x upper limit of normal

          -  Serum glutamate pyruvate transaminase (SGPT) =< 2 x upper limit of normal

          -  Able to sign informed consent

          -  Men and women of reproductive potential must agree to follow accepted birth control
             methods for the duration of the study. Female subject is either post-menopausal or
             surgically sterilized or willing to use an acceptable method of birth control (i.e., a
             hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with
             spermicide, or abstinence) for the duration of the study. Male subject agrees to use
             an acceptable method for contraception for the duration of the study

        Exclusion Criteria:

          -  Patient with active central nervous system (CNS) disease

          -  Pregnancy (positive beta human chorionic gonadotropin [HCG] test in a woman with child
             bearing potential defined as not post-menopausal for 12 months or no previous surgical
             sterilization) or currently breast-feeding. Pregnancy testing is not required for
             post-menopausal or surgically sterilized women

          -  Active hepatitis B, either active carrier (hepatitis B surface antigen positive [HBsAg
             +]) or viremic (hepatitis B virus [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

          -  Human immunodeficiency virus (HIV) infection

          -  Active uncontrolled bacterial, viral or fungal infections

          -  Exposure to other investigational drugs within 4 weeks before enrollment

          -  Grade >= 3 non-hematologic toxicity from previous therapy that has not resolved to =<
             grade 1

          -  Radiation therapy to head and neck (excluding eyes), and internal organs of chest,
             abdomen or pelvis in the month prior to enrollment

          -  Prior whole brain irradiation

          -  Prior autologous SCT in the prior 3 months

Maximum Eligible Age:	65 Years
Minimum Eligible Age:	12 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Progression-free survival
Time Frame:	Up to 3 years
Safety Issue:
Description:	Will be estimated by the method of Kaplan and Meier.

Secondary Outcome Measures

Measure:	Early treatment success
Time Frame:	Up to 100 days post-transplant
Safety Issue:
Description:	Will be defined as the compound event that the patient is alive, engrafted and in remission at 100 days post-transplant and does not experience grade 4 regimen-related toxicity or grade 4 acute graft versus host disease within 100 days post transplant. Will be tabulated and estimated.

Measure:	Overall survival
Time Frame:	Up to 4 years
Safety Issue:
Description:	Will be estimated by the method of Kaplan and Meier.

Measure:	Objective response rate
Time Frame:	Up to 100 days post-transplant
Safety Issue:
Description:	Will be tabulated and estimated.

Measure:	Complete response rate
Time Frame:	Up to 100 days post-transplant
Safety Issue:
Description:	Will be tabulated and estimated.

Details

Phase:	Phase 2
Primary Purpose:	Interventional
Overall Status:	Not yet recruiting
Lead Sponsor:	M.D. Anderson Cancer Center

Last Updated

January 9, 2020

Clinical Trials /

Vorinostat and Combination Chemotherapy Before Donor Stem Cell Transplantation for the Treatment of Relapsed Aggressive B-cell or T-cell Non-Hodgkin Lymphoma