High-Dose Gemcitabine, Busulfan and Melphalan for Patients With Refactory Hodgkin's Disease

NCT01200329 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2010-0142NCI-2012-01885
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if the combination of gemcitabine, busulfan, and melphalan, when given before a stem cell transplant, can help to control refractory Hodgkin's disease. The safety of this study treatment will also be studied.

Conditions

Lymphoma

Keywords

Hodgkin's disease; Relapsed; Refractory; High-dose chemotherapy; Busulfan; Gemcitabine; Melphalan

Outcome Measures

Primary Outcomes (1)

• Event-free Survival (EFS) of Patients

  The event-free survival (EFS) of patients with poor prognosis relapse or refractory Hodgkin's disease (HD) after high-dose chemotherapy (HDC) with Gemcitabine/Busulfan/Melphalan (GemBuMel). Event is defined as relapse, tumor progression or death.Progression free survival is the length of time during and after the treatment of disease that a patient lives with the disease but it does not get worse. Toxicity is defined as the treatment related mortality (TRM) rate, which will be evaluated within 30 days post transplant, and this rate will be compared with the 5% maximum rate. For EFS analysis, patients who experience the tumor relapse, disease progression, or death will be considered to be an event.

  Enrollment up to 2 years post transplant

Secondary Outcomes (1)

• Overall Survival (OS) of These Patients.

  Beyond 100 days post transplant up to 84 months.

Study Arms (1)

Gemcitabine + Busulfan + Melphalan

EXPERIMENTAL

Gemcitabine 2775 mg/m2 by vein over about 3 hours on days -8 and -3. Busulfan 32 mg/m2 test dose with PKs as outpatient and on day -10 as inpatient. AUC 4,000 by vein over about 3 hours on days -8 to -5. Melphalan 60 mg/m2 by vein over about 30 minutes on days -3 and -2. Palifermin 60 mg/kg by vein over 30 seconds daily, Days -12 to -10 and Days 0 to 2. Infusion of stem cells on Day 0.

Drug: Gemcitabine; Drug: Busulfan; Drug: Melphalan; Procedure: Stem Cell Transplantation; Drug: Palifermin

Interventions

Gemcitabine DRUG

2775 mg/m2 by vein over about 3 hours on days -8 and -3.

Also known as: Gemcitabine Hydrochloride, Gemzar

Gemcitabine + Busulfan + Melphalan

Busulfan DRUG

32 mg/m2 test dose with PKs as outpatient and on day -10 as inpatient AUC 4,000 by vein over about 3 hours on days -8 to -5.

Also known as: Busulfex, Myleran

Gemcitabine + Busulfan + Melphalan

Melphalan DRUG

60 mg/m2 by vein over about 30 minutes on days -3 and -2.

Also known as: Alkeran

Gemcitabine + Busulfan + Melphalan

Stem Cell Transplantation PROCEDURE

Infusion of stem cells on Day 0.

Also known as: SCT

Gemcitabine + Busulfan + Melphalan

Palifermin DRUG

60 mg/kg by vein over 30 seconds daily, Days -12 to -10 and Days 0 to 2.

Also known as: Kepivance

Gemcitabine + Busulfan + Melphalan

Eligibility Criteria

• Age: 12 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 12 to 70 years
• Patients with relapsed Hodgkin's disease and one or more of the following: 1) Less than complete response to first-line chemotherapy, 2) Relapse within 12 months of completion of first-line chemotherapy, 3) Relapse within a prior irradiation field, 4) Less than complete metabolic response to second-line chemotherapy, 5) Second relapse or beyond, 6) Extranodal disease at the time of relapse, 7) Presence of B symptoms at the time of persistent disease upon completion of first-line chemotherapy, or of relapse, progressive disease, 8) Bulky disease (defined as any lesion greater than 5 cm) at the time of persistent disease upon completion of first-line chemotherapy, or of relapse, progressive disease.
• Adequate renal function, as defined by estimated serum creatinine clearance \>/=50 ml/min (using the Cockcroft-Gault formula: creatinine clearance = \[(140-age)\*kg/(72\*serum creatinine)\] \* 0.85 if female) and/or serum creatinine \</=1.8 mg/dL.
• Adequate hepatic function, as defined by SGOT and/or SGPT \</=3 x upper limit of normal; serum bilirubin and alkaline phosphatase \</=2 x upper limit of normal, unless due to disease involvement
• Adequate pulmonary function with FEV1, FVC and DLCO \>/=50% of expected corrected for hemoglobin and/or volume.
• Adequate cardiac function with left ventricular ejection fraction \>/=40%. No uncontrolled arrhythmias or symptomatic cardiac disease.
• Zubrod performance status \<2.
• Negative Beta HCG text in a woman with child-bearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization

You may not qualify if:

• Patients with grade \>/= 3 non-hematologic toxicity from previous therapy that has not resolved to \</= grade 1.
• Patients with prior whole brain irradiation
• Patients with 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 the patient is receiving effective antiretroviral therapy with undetectable viral load and normal CD4 counts
• Patients having received radiation therapy to head and neck (excluding eyes), and internal organs of chest, abdomen or pelvis in the month prior to enrollment.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Nieto Y, Gruschkus S, Valdez BC, Jones RB, Anderlini P, Hosing C, Popat U, Qazilbash M, Kebriaei P, Alousi A, Saini N, Srour S, Rezvani K, Ramdial J, Barnett M, Gulbis A, Shigle TL, Ahmed S, Iyer S, Lee H, Nair R, Parmar S, Steiner R, Dabaja B, Pinnix C, Gunther J, Cuglievan B, Mahadeo K, Khazal S, Chuang H, Champlin R, Shpall EJ, Andersson BS. Improved outcomes of high-risk relapsed Hodgkin lymphoma patients after high-dose chemotherapy: a 15-year analysis. Haematologica. 2022 Apr 1;107(4):899-908. doi: 10.3324/haematol.2021.278311.

  PMID: 33951890 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Lymphoma; Hodgkin Disease; Recurrence

Interventions

Gemcitabine; Busulfan; Melphalan; Stem Cell Transplantation; Fibroblast Growth Factor 7

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Fibroblast Growth Factors; Intercellular Signaling Peptides and Proteins; Peptides; Proteins; Biological Factors

Results Point of Contact

• Title: Yago Nieto/Stem Cell Transplantation and Cellular Therapy
• Organization: UT MD Anderson Cancer Center

ynieto@mdanderson.org

713-792-8750

Study Officials

• Yago Nieto, MD, PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2010
• First Posted: September 13, 2010
• Study Start: June 1, 2011
• Primary Completion: December 6, 2018
• Study Completion: December 6, 2018
• Last Updated: December 16, 2019
• Results First Posted: December 16, 2019

Record last verified: 2019-12

Locations

US (1)