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An Intention-to-Treat Study of Salvage Chemotherapy Followed by Allogeneic Hematopoietic Stem Cell Transplant for the Treatment of High-Risk or Relapsed Hodgkin Lymphoma


Phase 2
13 Years
65 Years
Open (Enrolling)
Both
Lymphoma

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Trial Information

An Intention-to-Treat Study of Salvage Chemotherapy Followed by Allogeneic Hematopoietic Stem Cell Transplant for the Treatment of High-Risk or Relapsed Hodgkin Lymphoma


OBJECTIVES:

Primary

- To obtain a preliminary estimate of the progression-free survival at 1 year after
allogeneic hematopoietic stem cell transplantation.

Secondary

- To determine the speed of neutrophil and platelet recovery post allograft.

- To assess the incidence and speed of donor-derived engraftment post allograft.

- To assess the incidence and severity of acute graft-vs-host disease (GVHD) at 100 days
post allograft.

- To determine the incidence and severity of chronic GVHD at 1 year post allograft.

- To assess the incidence of transplant-related mortality at 100 and 180 days post
allograft.

- To assess the incidence of relapse or disease progression at 1 and 2 years post
allograft.

- To determine the probabilities of overall survival at 1 and 2 years post allograft for
all patients undergoing allograft.

- To determine the probabilities of progression-free survival at 2 years post allograft
for all patients undergoing allograft.

- To assess the number of patients enrolled on the intention-to-treat study proceeding to
allograft.

- To determine the probabilities of overall and progression-free survival at 1 and 2
years for all patients on the intention-to-treat study.

- To assess the performance of laboratory studies investigating double unit biology and
their correlation with unit engraftment in the patient.

OUTLINE: Patients are stratified according to response to prior therapy and risk factors
(those with presence of all 3 risk factors and failed primary therapy or primary progressive
disease vs. patients who relapse more than 100 days after an autologous stem cell
transplant).

- Salvage chemotherapy (IGV or MOPP): Patients who have previously received
mechlorethamine hydrochloride receive IGV; patients who have previously received a
gemcitabine-based regimen receive MOPP.

- IGV (ifosfamide, gemcitabine hydrochloride, and vinorelbine ditartrate): Patients
receive IGV combination chemotherapy comprising ifosfamide IV on days 1-4,
gemcitabine hydrochloride IV on days 1 and 4, and vinorelbine ditartrate IV on day
1. Treatment repeats every 2-3 weeks for 2-3 courses in the absence of disease
progression or unacceptable toxicity.

- MOPP (mechlorethamine hydrochloride, vincristine, procarbazine hydrochloride, and
prednisone): Patients receive MOPP combination chemotherapy comprising
mechlorethamine hydrochloride IV on days 1 and 8, vincristine IV on days 1 and 8,
oral procarbazine hydrochloride on days 1-14, and oral prednisone on days 1-14.
Treatment repeats every 4 weeks for at least 2 courses in the absence of disease
progression or unacceptable toxicity.

Patients with no progression of disease after salvage chemotherapy (at allograft work-up)
proceed to allogeneic hematopoietic stem cell transplantation [AHSCT]* within 60 days after
completion of salvage chemotherapy.

NOTE: *Patients with a nodal mass > 5 cm that has not ben previously irradiated and in the
absence of extranodal disease may undergo involved-field radiotherapy twice daily for 2
weeks, prior to AHSCT.

- AHSCT with reduced-intensity or non-myeloablative conditioning: Patients achieving
partial response or stable disease after salvage therapy receive fludarabine phosphate
IV over 30 minutes on days -6 to -2; melphalan IV over 15 minutes on days -6 and -5;
and undergo AHSCT on day 0 (reduced-intensity conditioning). Patients achieving
complete response after salvage therapy receive fludarabine phosphate IV over 30
minutes on days -6 to -2; cyclophosphamide IV over 15 minutes on day -6; total-body
irradiation over 20-30 minutes on day -1; and undergo AHSCT on day 0 (non-myeloablative
conditioning).

- Graft-vs-host disease prophylaxis: Patients with related or unrelated donors receive
cyclosporine IV over 2-4 hours or orally on days -3 to 100 followed by a taper,
mycophenolate mofetil IV or orally on days -3 to 46 followed by a taper, and
methotrexate IV on days 1, 3, 6, and 11.

Patients who received umbilical cord blood receive cyclosporine and mycophenolate mofetil as
above (no methotrexate).

After completion of study treatment, patients are followed at 6, 9, and 12 months and then
annually thereafter.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed classical Hodgkin lymphoma, including CD20+ disease

- No lymphocyte predominant histology

- Primary refractory or relapsed disease with all 3 risk factors, failed platinum-based
chemotherapy, or disease relapsed more than 100 days after autologous stem cell
transplantation, proven by biopsy or fine-needle aspiration (cytology) of an involved
site

- Risk factors are defined as B-symptoms, extranodal sites of disease, and disease
remission lasting < 1 year after first-line therapy

- Failed doxorubicin hydrochloride or mechlorethamine hydrochloride-containing
front-line therapy

- Fludeoxyglucose F 18-PET scan demonstrating PET-avid disease

- No more than 2 prior salvage chemotherapy regimens (for patients proceed to
allogeneic hematopoietic stem cell transplantation [AHSCT])

- Donor available meeting 1 of the following criteria (for patients proceed to AHSCT):

- HLA-matched or one allele mismatched related donor

- Genotypically or phenotypically matched at ≥ 9/10 of the A, B, C, DRB1, and
DQB1 loci, as tested by high resolution

- Peripheral blood stem cells (PBSC) collected

- HLA-matched unrelated donor

- Matched at ≥ 9/10 (allele mismatch only) of the A, B, C, DRB1, and DQB1
loci, as tested by high resolution

- PBSC or bone marrow collected

- Umbilical cord blood (2 units)

- must be ≥ 4/6 HLA-A, B antigen, and DRB1 allele matched with recipient

PATIENT CHARACTERISTICS:

- Platelet count > 50,000/mm^3

- ANC > 1,000/mm^3

- Cardiac ejection fraction > 50% (for patients ≥ 18 years of age)

- Fractional shortening > 50% by echocardiogram* (for patients < 18 years of age)

- Adjusted diffusing capacity > 50% on pulmonary function testing*

- Serum creatinine < 1.5 mg/dL

- Creatinine clearance ≥ 50 mL/min

- Total bilirubin < 2.0 mg/dL in the absence of a history of Gilbert disease

- HIV I and II negative

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Karnofsky performance status (PS) ≥ 70% or Lansky PS ≥ 70% (for patients proceed to
AHSCT)

- No active and uncontrolled infection at time of transplantation including active
infection with Aspergillus or other mold (for patients proceed to AHSCT) NOTE:
*measured since last chemotherapy

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior allogeneic transplantation

- No more than 1 prior autologous transplantation

- No inability to complete planned cytoreduction due to therapy complications

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival at 1 year

Outcome Time Frame:

1 year

Safety Issue:

No

Principal Investigator

Miguel-Angel Perales, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

07-147

NCT ID:

NCT00574496

Start Date:

November 2007

Completion Date:

November 2017

Related Keywords:

  • Lymphoma
  • recurrent adult Hodgkin lymphoma
  • recurrent/refractory childhood Hodgkin lymphoma
  • adult lymphocyte depletion Hodgkin lymphoma
  • adult nodular sclerosis Hodgkin lymphoma
  • adult mixed cellularity Hodgkin lymphoma
  • childhood lymphocyte depletion Hodgkin lymphoma
  • childhood mixed cellularity Hodgkin lymphoma
  • childhood nodular sclerosis Hodgkin lymphoma
  • stage III adult Hodgkin lymphoma
  • stage IV adult Hodgkin lymphoma
  • stage III childhood Hodgkin lymphoma
  • stage IV childhood Hodgkin lymphoma
  • Hodgkin Disease
  • Lymphoma

Name

Location

Memorial Sloan-Kettering Cancer CenterNew York, New York  10021