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

Phase 2
18 Years
72 Years
Not Enrolling

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Trial Information

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



- 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.


- 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

- 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

- 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

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

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

- 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

Type of Study:


Study Design:

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

Outcome Measure:

Event-free survival at 3 years

Outcome Time Frame:

3 years

Safety Issue:


Principal Investigator

Craig Moskowitz, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

April 2004

Completion Date:

July 2012

Related Keywords:

  • Lymphoma
  • adult lymphocyte depletion Hodgkin lymphoma
  • adult mixed cellularity Hodgkin lymphoma
  • adult nodular sclerosis Hodgkin lymphoma
  • recurrent adult Hodgkin lymphoma
  • Hodgkin Disease
  • Lymphoma



Memorial Sloan-Kettering Cancer CenterNew York, New York  10021