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Recurrent Aggressive Non-Hodgkin LymphomaPhase 2NCT04220008

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

A Phase 2 study testing Allogeneic Hematopoietic Stem Cell Transplantation, Busulfan and Clofarabine in people with Recurrent Aggressive Non-Hodgkin Lymphoma and Recurrent B-Cell Non-Hodgkin Lymphoma, run by M.D. Anderson Cancer Center.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

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). Read more about this study

Who is it for?
Ages 12 to 65 years
What is being tested?
Allogeneic Hematopoietic Stem Cell Transplantation, Busulfan and Clofarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
29 Oct 2021to 29 Oct 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 to 65 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

About this study

Official title: Vorinostat With Gemcitabine/Clofarabine/Busulfan for Allogeneic Transplantation for Aggressive Lymphomas

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. Estimate the progression-free survival (PFS) time.

SECONDARY OBJECTIVES:

  1. 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.

  1. 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.

  1. 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:

  1. 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.

Medical subject headings
Lymphoma, B-Cell, Burkitt Lymphoma, Lymphoma, Large B-Cell, Diffuse, Lymphoma, T-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery

    Also called Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT

    Undergo allogeneic HSCT

  • BusulfanDrug

    Also called 1, 4-Bis[methanesulfonoxy]butane, BUS, Bussulfam, Busulfanum

    Given IV

  • ClofarabineDrug

    Also called Clofarex, Clolar

    Given IV

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • GemcitabineDrug

    Also called dFdC, dFdCyd, Difluorodeoxycytidine

    Given IV

  • Mycophenolate MofetilDrug

    Also called Cellcept, MMF

    Given IV

  • RituximabBiological

    Also called ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody

    Given IV

  • TacrolimusDrug

    Also called FK 506, Fujimycin, Hecoria, Prograf

    Given IV

  • VorinostatDrug

    Also called L-001079038, MSK-390, SAHA, Suberanilohydroxamic Acid

    Given PO

Study groups in NCT04220008
Study groupRoleWhat they receive
Treatment (busulfan, vorinostat, gemcitabine, clofarabine)ExperimentalPatients 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
Receives: Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Busulfan; Drug: Clofarabine; Drug: Cyclophosphamide; Drug: Gemcitabine; Drug: Mycophenolate Mofetil; Biological: Rituximab; Drug: Tacrolimus; Drug: Vorinostat

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free survival

    Will be estimated by the method of Kaplan and Meier.

    Measured: Up to 3 years

Secondary outcomes (4)

  1. Early treatment success

    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.

    Measured: Up to 100 days post-transplant

  2. Overall survival

    Will be estimated by the method of Kaplan and Meier.

    Measured: Up to 4 years

  3. Objective response rate

    Will be tabulated and estimated.

    Measured: Up to 100 days post-transplant

  4. Complete response rate

    Will be tabulated and estimated.

    Measured: Up to 100 days post-transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jan 2020
  2. Study start29 Oct 2021
  3. Primary completion29 Oct 2021
  4. Study completion29 Oct 2021

Why it stopped: No Participants Enrolled

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04220008
Sponsor's protocol ID
2018-0988
Other IDs
NCI-2019-08496, 2018-0988
Status last verified
Jan 2024
First submitted
3 Jan 2020
Last updated
12 Jan 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Allogeneic Hematopoietic Stem Cell Transplantation, Busulfan and Clofarabine in people with Recurrent Aggressive Non-Hodgkin Lymphoma and Recurrent B-Cell Non-Hodgkin Lymphoma, run by M.D. Anderson Cancer Center.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 12 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (time frame: Up to 3 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04220008.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jan 2024.

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