Combination Chemotherapy and Radiation Therapy in Treating Patients Who Are Undergoing an Autologous Stem Cell Transplant for Relapsed or Refractory Hodgkin's Lymphoma

Lymphoma Clinical Trial

Official title:

Risk-Adapted High Dose Chemoradiotherapy and Autologous Stem Cell Transplantation for Patients With Relapsed and Primary Refractory Hodgkin's Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00255723
• Other study ID #: 04-047
• Secondary ID: MSKCC-04047
• Status: Completed
• Phase: Phase 2
• First received: November 18, 2005
• Last updated: December 22, 2015
• Start date: April 2004
• Est. completion date: July 2012

Study information

• Verified date: December 2015
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Radiation therapy uses high-energy x-rays to kill cancer cells. Giving combination chemotherapy and radiation therapy with an autologous stem cell transplant, using peripheral stem cells or bone marrow from the patient, may allow more chemotherapy to be given so that more cancer cells are killed. Giving combination chemotherapy together with radiation therapy before an autologous stem cell transplant may be an effective treatment for Hodgkin's lymphoma.

PURPOSE: This phase II trial is studying how well combination chemotherapy and radiation therapy work in treating patients who are undergoing an autologous stem cell transplant for relapsed or refractory Hodgkin's lymphoma.

Description:

OBJECTIVES:

Primary

• Determine whether event-free survival of patients with low to high-intermediate risk, relapsed or refractory Hodgkin's lymphoma can be improved when treated with cytoreductive combination chemotherapy followed by radiotherapy, high-dose combination chemotherapy, and autologous stem cell transplantation.

Secondary

• Determine the toxic effects of this regimen in these patients.

OUTLINE: Patients are stratified according to risk factors (low or low-intermediate risk [0-1 risk factor] vs high-intermediate risk [2 risk factors]).

• ICE-based cytoreductive chemotherapy: Patients are assigned to 1 of 2 treatment groups.

• Group I (patients with low or low-intermediate risk disease): Patients receive ICE comprising ifosfamide IV and carboplatin IV once on day 2 and etoposide IV over 1 hour once daily on days 1-3. Patients then receive ifosfamide IV twice on day 15, carboplatin IV once on day 17 and etoposide IV over 1 hour twice daily on days 15-17.

• Group II (patients with high-intermediate risk disease): Patients receive ifosfamide IV twice on days 1 and 17, carboplatin IV once on days 3 and 19, and etoposide IV over 1 hour twice daily on days 1-3 and 17-19.

In both groups, patients undergo stem cell collection after either the first or second OR first and second courses of ICE.

• Stem cell mobilization and collection: Patients receive filgrastim (G-CSF) subcutaneously (SC) beginning on day 5 and continuing until stem cell collection is completed. Patients undergo a maximum of 5 daily apheresis sessions. Patients who mobilize fewer than the required minimal number of stem cells repeat apheresis with high-dose G-CSF alone or undergo bone marrow harvest. Patients then proceed to radiotherapy, high-dose chemotherapy (HDC), and autologous stem cell transplant (ASCT) OR noncross-resistant chemotherapy based on response to ICE-based cytoreductive chemotherapy.

• Restaging studies: Patients undergo restaging studies with CT scan and positron emission tomography (PET). Patients who are chemosensitive with a normal PET scan proceed to radiotherapy, HDC, and ASCT. Patients who progress on ICE, or who respond but have an abnormal PET scan, proceed to noncross-resistant chemotherapy comprising gemcitabine hydrochloride, vinorelbine, and doxorubicin HCl liposome (GND).

• GND chemotherapy: Patients receive gemcitabine hydrochloride IV, vinorelbine IV, and doxorubicin HCl liposome IV on days 1, 15, 29, and 43. Patients then proceed to radiotherapy, HDC, and ASCT in the absence of disease progression.

• Radiotherapy: Within 2 weeks after completion of the ICE or GND regimen, patients who have no history of prior radiotherapy receive radiotherapy according to stratification by disease extent (isolated lymph nodes vs ≥ 2 contiguous nodal-based masses with or without extensive small-volume lymphadenopathy vs extensive small-volume lymphadenopathy). These patients undergo either involved-field radiotherapy (IFRT) twice daily over 1-2 weeks, total lymphoid irradiation (TLI) twice daily over 1 week, or both concurrently.

• HDCT: Patients who undergo TLI only OR IFRT and TLI receive high-dose cyclophosphamide IV twice daily and etoposide IV once daily on days -5 and -2. Patients who undergo IFRT only OR do not undergo radiotherapy receive high-dose cyclophosphamide IV twice daily and etoposide IV once daily on days -6 and -3 and carmustine IV once on day -2.

• ASCT: Patients undergo ASCT or reinfusion of bone marrow, if harvested, on day -1 or 0. Patients then receive G-CSF beginning on day 5 and continuing until blood counts recover.

After completion of study treatment, patients are followed periodically for 15 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 98
• Est. completion date: July 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 72 Years

Eligibility

Inclusion Criteria:

• Histologic diagnosis of Classical Hodgkin's Lymphoma. Lymphocyte predominant histology will be excluded.

• Primary refractory or relapsed disease proven by biopsy or fine needle aspiration (cytology) of an involved site

• Failure of doxorubicin or nitrogen mustard containing front-line therapy

• 18F-fluorodeoxyglucose-PET scan demonstrating PET avid disease

• Cardiac ejection fraction of greater than 45%, measured since last chemotherapy.

• Adjusted diffusing capacity of greater than 50% on pulmonary function testing, measured since last chemotherapy

• Serum creatinine < than or = to 1.5 mg/dl; if creatinine >1.5 mg/dl then the measured 12- or 24-hour creatinine clearance must be >60 ml/minute.

• ANC>1000/µl and Platelets>50,000/µl

• Total bilirubin < than or = to 2.0 mg/dl in the absence of a history of Gilbert's disease.

• Females of childbearing age must be on an acceptable form of birth control.

• Age between 18 and 72

• HIV I and II negative.

• Patients or their guardians must be capable of providing informed consent.

Exclusion Criteria:

Histology for Lymphocyte predominant subtype Hodgkin's Lymphoma

• Prior treatment with carboplatin, cisplatin, ifosfamide, gemcitabine, or vinorelbine

• Hepatitis B surface antigen positive.

• Known pregnancy or breast-feeding.

• Medical illness unrelated to Hodgkin's Lymphoma, which, in the opinion of the attending physician and/or principal investigator, will preclude administering chemotherapy safely.

• History of any malignancy for which the disease-free interval is <5 years, excluding curatively treated cutaneous basal cell or squamous cell carcinoma and carcinoma in-situ of the cervix

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hodgkin Disease
• Lymphoma

Intervention

Drug:
• carboplatin
Given IV
• etoposide
Given IV
• ifosfamide
Given IV

Locations

Country	Name	City	State
United States	Memorial Sloan-Kettering Cancer Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Objective Response	Overall objective response to therapy Complete remission/unconfirmed (CRu); This includes patients who meet criteria for CR with the following exceptions: 1. A residual lymph node mass > 1.5 cm in the short axis with normalization of 18Ffluorodeoxyglucose- PET scan Partial remission/minimal response (PR and MR); Any decrease in lymph nodes and nodal-based masses; Any decrease in PET avidity (however, residual FDG uptake is present); Involving organs involved prior to therapy must have diminished in size.; No new sites of disease Stable disease Response is less than that which constitutes a PR and disease does not meet criteria for progressive disease Progressive disease; 1. Increase in lymph nodes or nodal-based masses, or other measurable disease from pretreatment observations. 2. Appearance of any new lesion at the end of therapy	3 years	No