Vorinostat + Chemotherapy Before Stem Cell Transplant for Non-Hodgkin's Lymphoma

Recruiting in Palo Alto (17 mi)

Overseen byYago L Nieto

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: M.D. Anderson Cancer Center

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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.

Research Team

Yago L Nieto

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with aggressive B-cell or T-cell non-Hodgkin lymphoma that has relapsed. Participants need a matched donor for stem cell transplantation, good heart and lung function, normal liver tests, and must use birth control. It's not open to those with severe liver damage, HIV, uncontrolled infections, recent brain irradiation or stem cell transplant, active CNS disease, pregnancy/breastfeeding women, hepatitis B carriers or those on other investigational drugs.

Inclusion Criteria

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%

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

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Exclusion Criteria

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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Treatment Details

Interventions

Busulfan (Alkylating Agent)
Clofarabine (Antimetabolite)
Cyclophosphamide (Alkylating Agent)
Gemcitabine (Antimetabolite)
Rituximab (Immunotherapy)
Tacrolimus (Immunosuppressant)
Vorinostat (Histone Deacetylase Inhibitor)

Trial OverviewThe study is testing the effectiveness of vorinostat combined with chemotherapy (busulfan, gemcitabine & clofarabine) before undergoing donor stem cell transplantation in controlling relapsed lymphoma. Vorinostat targets cancer growth enzymes while the chemo drugs work to kill or stop cancer cells from growing.

Participant Groups

1Treatment groups

Experimental Treatment

Group I: Treatment (busulfan, vorinostat, gemcitabine, clofarabine)Experimental Treatment9 Interventions

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 is already approved in Canada, Japan for the following indications: