Know Cancer

or
forgot password

A Phase I/II Study of Autologous Stem Cell Transplantation Followed by Nonmyeloablative Allogeneic Stem Cell Transplantation for Patients With Relapsed or Refractory Lymphoma - A Multi-Center Trial


Phase 1/Phase 2
N/A
75 Years
Open (Enrolling)
Both
Adult Nasal Type Extranodal NK/T-cell Lymphoma, Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell Lymphoma, Burkitt Lymphoma, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Nodal Marginal Zone B-cell Lymphoma, Prolymphocytic Leukemia, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma, Recurrent Adult Diffuse Small Cleaved Cell Lymphoma, Recurrent Adult Grade III Lymphomatoid Granulomatosis, Recurrent Adult Hodgkin Lymphoma, Recurrent Adult Immunoblastic Large Cell Lymphoma, Recurrent Adult Lymphoblastic Lymphoma, Recurrent Adult T-cell Leukemia/Lymphoma, Recurrent Childhood Grade III Lymphomatoid Granulomatosis, Recurrent Childhood Large Cell Lymphoma, Recurrent Childhood Lymphoblastic Lymphoma, Recurrent Childhood Small Noncleaved Cell Lymphoma, Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Mycosis Fungoides/Sezary Syndrome, Recurrent Small Lymphocytic Lymphoma, Recurrent/Refractory Childhood Hodgkin Lymphoma, Refractory Chronic Lymphocytic Leukemia, Splenic Marginal Zone Lymphoma, Waldenstrom Macroglobulinemia

Thank you

Trial Information

A Phase I/II Study of Autologous Stem Cell Transplantation Followed by Nonmyeloablative Allogeneic Stem Cell Transplantation for Patients With Relapsed or Refractory Lymphoma - A Multi-Center Trial


PRIMARY OBJECTIVES:

I. To evaluate engraftment of human leukocyte antibody (HLA) identical peripheral blood stem
cell (PBSC) allografts given after conditioning with total-body irradiation (TBI) (200cGy)
+/- fludarabine, 90 mg/m^2 and post-grafting immunosuppression with cyclosporine
(CSP)/mycophenolate mofetil (MMF) in refractory or relapsed lymphoma patients following an
initial autologous peripheral blood stem cell transplant (PBSCT) for disease cytoreduction.

II. To determine the non-relapse mortality at day 100 post-non-myeloablative allografting
following mobilization and high-dose chemotherapy with autografting.

SECONDARY OBJECTIVES:

I. To determine the disease free survival and overall survival of non-myeloablative
allografting following autologous PBSCT.

OUTLINE:

CONDITIONING REGIMEN: Patients with matched, related stem cell donors receive
cyclophosphamide intravenously (IV) on days -6 and -5 and undergo TBI twice daily (BID) on
days -3 to -1. Patients with matched, unrelated stem cell donors receive carmustine IV over
3 hours on day -7, etoposide IV over 2 hours BID on days -6 to -3, and cytarabine IV over 3
hours BID on days -6 to -3, and melphalan IV over 30 minutes on day -2.

TRANSPLANTATION: All patients undergo autologous PBSCT on day 0.

NON-MYELOABLATIVE CONDITIONING: Beginning 40-120 days following PBSC transplant, patients
with related donors undergo TBI on day 0. Patients with unrelated donors receive fludarabine
IV over 30 minutes on days -4 to -2 and undergo TBI on day 0.

TRANSPLANTATION: Patients undergo non-myeloablative allogeneic PBSCT on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) BID on days -3 to 56 (patients
with related donors) or 100 (patients with unrelated donors) followed by taper to day 180.
Patients also receive mycophenolate mofetil PO BID on days 0-27 (patients with related
donors) or thrice daily (TID) on days 0-27, then BID on days 28-40 followed by taper to day
96 (patients with unrelated donors).

Some patients may undergo donor lymphocyte infusion if there is evidence of disease
progression and no evidence of graft-vs-host disease (GVHD).

After completion of study treatment, patients are followed up at 1, 1.5, 2, and 3 years and
then annually thereafter.


Inclusion Criteria:



- Patients with lymphoma (non-Hodgkin lymphoma [NHL], chronic lymphocytic
leukemia/small lymphocytic lymphoma [CLL/SLL] or Hodgkin lymphoma) with primary
refractory or relapsed disease after standard chemotherapy at high risk of relapse
with conventional autografting; patients with a diagnosis of CLL (or small
lymphocytic lymphoma) or diagnosis of CLL that progresses to prolymphocytic leukemia
(PLL), or T-cell CLL or PLL

- Must have an HLA genotypically or phenotypically identical related donor or, at a
minimum, a high likelihood of identifying an HLA-matched unrelated donor; the
determination of availability of a suitable unrelated donor may be based on a
World-Book search

- Cross-over to other tandem autologous-allogeneic research protocol (#2241) will be
allowed if the patient loses the suitable HLA-matched related or unrelated donor but
has an available HLA-haploidentical donor before receiving the allogeneic
transplantation and if the patient meets the eligibility criteria of the subsequent
study

- Cross-over from other tandem autologous-allogeneic research protocol (#2241) will be
allowed if a suitable HLA-matched related or unrelated donor is identified before
receiving the allogeneic transplantation and if the patient meets the eligibility
criteria of the subsequent study

- Signed informed consent

- Detectable tumor on radiographic studies or bone marrow biopsy prior to mobilization
regimen

- Expected survival >= 3 months from study entry

- DONOR: HLA genotypically or phenotypically identical related donor

- DONOR: must consent to G-CSF administration and leukapheresis for both PBSC allograft
and subsequent donor lymphocyte infusion (DLI)

- DONOR: must have adequate veins for leukapheresis or agree to placement of central
venous catheter (femoral or subclavian)

- DONOR: Age < 75 yrs, older donors may be considered after review at Patient Care
Conference

- DONOR: Fred Hutchinson Cancer Research Center (FHCRC) matching allowed will be Grades
1.0 to 2.1; unrelated donors who are prospectively: Matched for HLA-A, B, C, DRB1 and
DQB1 by high resolution typing; only a single allele disparity will be allowed for
HLA-A, B, or C as defined by high resolution typing

- DONOR: Donors are excluded when preexisting immunoreactivity is identified that would
jeopardize donor hematopoietic cell engraftment; this determination is based on the
standard practice of the individual institution; the recommended procedure for
patients with 10 of 10 HLA allele level (phenotypic) match is to obtain a panel
reactive antibody (PRA) screens to class I and class II antigens for all patients
before HCT; if the PRA shows > 10% activity, then flow cytometric or B and T cell
cytotoxic cross matches should be obtained; the donor should be excluded if any of
the cytotoxic cross match assays are positive; for those patients with an HLA Class I
allele mismatch, flow cytometric or B and T cell cytotoxic cross matches should be
obtained regardless of the PRA results; a positive anti-donor cytotoxic crossmatch is
an absolute donor exclusion

- DONOR: patient and donor pairs homozygous at a mismatched allele in the graft
rejection vector are considered a two-allele mismatch, i.e., the patient is A*0101
and the donor is A*0102, and this type of mismatch is not allowed

- DONOR: Only G-CSF mobilized peripheral blood mononuclear cells (PBMC) only will be
permitted as a hematopoietic stem cell (HSC) source on this protocol

Exclusion Criteria:

- Life expectancy severely limited by disease other than lymphoma

- Prior autologous hematopoietic stem cell transplant

- Patients at high risk of veno-occlusive disease of the liver (criteria not yet
rigorously defined but includes bilirubin > 2.0 mg and serum glutamic oxaloacetic
transaminase [SGOT] or serum glutamic pyruvate transaminase [SGPT] > 2 x normal);
patients may be accepted outside of this range if cleared by gastrointestinal (GI)
consult

- Cardiac ejection fraction (EF) < 40% on multi-gated acquisition (MUGA) scan or
cardiac echo (or if unable to obtain ejection fraction, shortening fraction of <
26%); patients with active or a history of cardiac disease should be evaluated with
appropriate cardiac studies and/or consult; ejection fraction is required if age > 50
years or there is a history of anthracyclines or history of cardiac disease; patients
with a shortening fraction < 26% may be enrolled if approved by a cardiologist

- Baseline serum-creatinine > 2.0 mg/dl and a calculated or measured creatinine
clearance of < 50 ml/minute

- Seropositive for the human immunodeficiency virus (HIV)

- Pulmonary dysfunction as measured by a corrected diffusing capacity of the lung for
carbon monoxide (DLCO) < 50% of predicted total lung capacity (TLC) < 30%, forced
expiratory volume in 1 second (FEV1) < 30% and/or receiving supplementary continuous
oxygen; the FHCRC primary investigator (PI) of the study must approve enrollment of
all patients with pulmonary nodules

- Pregnancy or breast-feeding

- Radiation therapy to mediastinum within 3 months prior to enrollment

- Patients with poorly controlled hypertension despite hypertensive medication

- Karnofsky score < 60; pediatric criteria: Lansky Play-Performance Score < 40

- Patients with cluster of differentiation (CD)34 selected auto grafts

- Patients with active non-hematologic malignancies (except nonmelanoma skin cancers);
this exclusion does not apply to patients with non-hematologic malignancies that do
not require therapy

- Patients with a history of non-hematologic malignancies (except nonmelanoma skin
cancers) currently in a complete remission, who are less than 5 years from the time
of complete remission, and have a > 20% risk of disease recurrence; this exclusion
does not apply to patients with non-hematologic malignancies that do not require
therapy

- DONOR: Identical twin

- DONOR: Age less than 12 years

- DONOR: Pregnancy

- DONOR: HIV seropositivity

- DONOR: Inability to achieve adequate venous access

- DONOR: Known allergy to G-CSF

- DONOR: Current serious systemic illness

- DONOR: Failure to meet FHCRC criteria for stem cell donation

- DONOR: Donor (or centers) who will exclusively donate marrow

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Engraftment of HLA identical PBSC allografts

Outcome Description:

The rates and accompanying confidence intervals associated with failure of engraftment at day +56 will be calculated after every 5th patient is enrolled on the study. If the lower limit to the appropriate one-sided 80% confidence interval exceeds 25%, this will be considered sufficient evidence of an excess "failure" rate and the study will be stopped. For these purposes, all patients will be evaluated together (patients with chemosensitive and chemoresistant disease).

Outcome Time Frame:

Day 56

Safety Issue:

Yes

Principal Investigator

David Maloney

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Authority:

United States: Federal Government

Study ID:

1409.00

NCT ID:

NCT00005803

Start Date:

September 1999

Completion Date:

Related Keywords:

  • Adult Nasal Type Extranodal NK/T-cell Lymphoma
  • Anaplastic Large Cell Lymphoma
  • Angioimmunoblastic T-cell Lymphoma
  • Burkitt Lymphoma
  • Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
  • Nodal Marginal Zone B-cell Lymphoma
  • Prolymphocytic Leukemia
  • Recurrent Adult Burkitt Lymphoma
  • Recurrent Adult Diffuse Large Cell Lymphoma
  • Recurrent Adult Diffuse Mixed Cell Lymphoma
  • Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
  • Recurrent Adult Grade III Lymphomatoid Granulomatosis
  • Recurrent Adult Hodgkin Lymphoma
  • Recurrent Adult Immunoblastic Large Cell Lymphoma
  • Recurrent Adult Lymphoblastic Lymphoma
  • Recurrent Adult T-cell Leukemia/Lymphoma
  • Recurrent Childhood Grade III Lymphomatoid Granulomatosis
  • Recurrent Childhood Large Cell Lymphoma
  • Recurrent Childhood Lymphoblastic Lymphoma
  • Recurrent Childhood Small Noncleaved Cell Lymphoma
  • Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
  • Recurrent Grade 1 Follicular Lymphoma
  • Recurrent Grade 2 Follicular Lymphoma
  • Recurrent Grade 3 Follicular Lymphoma
  • Recurrent Mantle Cell Lymphoma
  • Recurrent Marginal Zone Lymphoma
  • Recurrent Mycosis Fungoides/Sezary Syndrome
  • Recurrent Small Lymphocytic Lymphoma
  • Recurrent/Refractory Childhood Hodgkin Lymphoma
  • Refractory Chronic Lymphocytic Leukemia
  • Splenic Marginal Zone Lymphoma
  • Waldenström Macroglobulinemia
  • Burkitt Lymphoma
  • Hodgkin Disease
  • Immunoblastic Lymphadenopathy
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Leukemia, Prolymphocytic
  • Leukemia, T-Cell
  • Leukemia-Lymphoma, Adult T-Cell
  • Lymphoma
  • Lymphoma, Follicular
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Lymphomatoid Granulomatosis
  • Waldenstrom Macroglobulinemia
  • Mycoses
  • Mycosis Fungoides
  • Sezary Syndrome
  • Lymphoma, B-Cell
  • Lymphoma, Large-Cell, Immunoblastic
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Lymphoma, T-Cell
  • Lymphoma, T-Cell, Cutaneous
  • Lymphoma, Large-Cell, Anaplastic
  • Lymphoma, B-Cell, Marginal Zone
  • Lymphoma, Extranodal NK-T-Cell
  • Lymphoma, Mantle-Cell

Name

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattle, Washington  98109
VA Puget Sound Health Care SystemSeattle, Washington  98101