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A Pilot Study of Irradiated HLA-Partially Matched Allogeneic Related Donor Lymphocytes in Conjunction With Rituximab for Selected Patients With CD20 + Malignancies


N/A
18 Years
N/A
Not Enrolling
Both
Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm

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Trial Information

A Pilot Study of Irradiated HLA-Partially Matched Allogeneic Related Donor Lymphocytes in Conjunction With Rituximab for Selected Patients With CD20 + Malignancies


OBJECTIVES:

Primary

- Determine the toxicity of irradiated HLA-partially matched related donor lymphocytes
when administered with rituximab in patients with relapsed or refractory CD20-positive
lymphoproliferative disease.

- Determine the efficacy of this regimen in these patients.

Secondary

- Correlate response with Fc receptor FcγIIIA polymorphisms or predicted HLA-directed
natural killer cell reactivity.

OUTLINE: This is a pilot study.

- Rituximab therapy: Patients receive rituximab IV on days -1, 6, 13, and 20. Treatment
repeats approximately every 4 months in the absence of disease progression or
unacceptable toxicity.

- Donor lymphocyte infusion: Patients receive irradiated donor lymphocytes IV over 1 hour
on day 0. Treatment repeats every 8-16 weeks (alternating with courses of rituximab
therapy) for up to 6 donor lymphocyte infusions in the absence of disease progression
or unacceptable toxicity.

Peripheral blood is collected periodically during study for correlative laboratory studies.
Blood samples are analyzed for FcγIIIA polymorphism by fluorescent in situ hybridization or
by reverse transcriptase-polymerase chain reaction. Survival of donor lymphocytes is
assessed by chimerism studies.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed lymphoproliferative disease

- CD20-positive disease

- Bidimensionally measurable disease OR abnormal cells detected in blood

- Resistant or refractory to standard therapies and/or unlikely to benefit from
additional standard therapies* AND meets 1 of the following criteria:

- Disease with anticipated response rate < 20% after treatment with rituximab
alone, including any of the following:

- Diffuse large cell lymphoma

- B-cell lymphoblastic lymphoma

- Burkitt's lymphoma

- Acute lymphocytic leukemia

- Relapsed or progressive disease after prior treatment with rituximab, including
any of the following:

- Hodgkin's lymphoma

- Hairy cell leukemia

- Chronic lymphocytic leukemia/small lymphocytic lymphoma meeting any of the
following criteria:

- Received prior fludarabine phosphate-containing regimens and relapsed
within 1 year of treatment OR ineligible to receive such therapy due
to comorbidities or allergies

- Received prior anti-CD52 monoclonal antibody therapy and relapsed
within 1 year of treatment OR ineligible to receive such therapy (for
patients without symptomatic lymphadenopathy)

- Has documentation of disease-associated symptoms, rapid disease
progression, or other indications for treatment

- B-cell prolymphocytic leukemia meeting any of the following criteria:

- Received prior fludarabine phosphate- or alkylating agent-containing
regimens and relapsed within 1 year of treatment OR ineligible to
receive such therapy due to comorbidities or allergies

- Received prior anti-CD52 monoclonal antibody therapy OR ineligible to
receive such therapy (for patients without symptomatic
lymphadenopathy)

- Lymphoplasmacytic lymphoma, marginal zone lymphoma, mucosa-associated
lymphoid tissue lymphoma, or follicular lymphoma meeting any of the
following criteria:

- Received prior fludarabine phosphate- and/or alkylating
agent-containing regimens and relapsed within 1 year of treatment OR
ineligible to receive such therapy due to comorbidities or allergies

- Received prior anti-CD20 monoclonal antibody therapy and relapsed
within 1 year of treatment OR ineligible to receive such therapy

- Received prior radioconjugated anti-CD20 monoclonal antibody therapy
OR ineligible to receive such therapy

- Has documentation of disease-associated symptoms, rapid disease
progression, or other indications for treatment

- Multiple myeloma meeting any of the following criteria:

- Received prior alkylating agent-, thalidomide-, corticosteroid-, or
bortezomib-containing regimens and relapsed after 1 year of treatment
OR ineligible to receive such therapies due to comorbidities or
allergies

- Received prior high-dose chemotherapy followed by autologous
hematopoietic stem cell rescue and relapsed after treatment OR
ineligible to receive such therapy

- Mantle cell lymphoma meeting the following criteria:

- Received prior combination chemotherapy and anti-CD20 monoclonal
antibody therapy and relapsed after treatment OR ineligible to receive
such therapy

- Diffuse large B-cell lymphoma meeting any of the following criteria:

- Received prior combination chemotherapy and relapsed after treatment
OR ineligible to receive such therapy

- Received prior salvage combination chemotherapy with or without
high-dose chemotherapy followed by autologous hematopoietic stem cell
rescue and relapsed after treatment OR not a candidate to receive such
therapy

- Received prior radiolabeled anti-CD20 monoclonal antibody therapy for
transformed large cell lymphoma OR ineligible to receive such therapy

- Burkitt's lymphoma meeting any of the following criteria:

- Received prior combination chemotherapy and relapsed after treatment
OR ineligible to receive such therapy

- Received prior salvage combination chemotherapy with or without
high-dose chemotherapy followed by autologous hematopoietic stem cell
rescue and relapsed after treatment OR ineligible to receive such
therapy

- Lymphomatoid granulomatosis meeting any of the following criteria:

- Received prior single-agent or combination chemotherapy and relapsed
after treatment OR ineligible to receive such therapy

- Has documentation of disease-associated symptoms, rapid disease
progression, or other indications for treatment

- Acute lymphocytic leukemia meeting any of the following criteria:

- Received prior multi-agent combination chemotherapy administered in
sequential induction, consolidation, and maintenance courses and
relapsed during or after treatment OR ineligible to receive such
therapy

- Received prior chemotherapy with or without radiotherapy followed by
allogeneic hematopoietic stem cell transplantation (HSCT) and relapsed
after treatment OR not a candidate for such therapy

- Received prior treatment with chemotherapy with or without
radiotherapy followed by allogeneic HSCT and relapsed after treatment
(or not a candidate for such therapy) AND demonstrates persistent
cytogenetic, fluorescent in situ hybridization, or molecular (reverse
transcriptase-polymerase chain reaction) evidence of the bcr-abl
fusion gene despite 6 weeks of treatment with imatinib mesylate NOTE:
*Not eligible to receive standard available salvage regimens
anticipated to result in durable remission

- No active CNS malignancy

- Not considered a candidate for allogeneic HSCT

- HLA-partially matched (≥ 2/6) related donor available

PATIENT CHARACTERISTICS:

- ECOG performance status 0-1

- Life expectancy > 3 months

- Not pregnant

- Negative pregnancy test

- Fertile women must use effective contraception

- Bilirubin < 1.5 times upper limit of normal (ULN)

- AST < 3.0 times ULN

- Cardiac ejection fraction > 35%

- Absolute neutrophil count > 1,000/mm³ (without cytokines)

- Platelet count > 50,000/mm³ (untransfused)

- No significant organ dysfunction

- No active uncontrolled infections

- No hypersensitivity reaction to rituximab that has precluded completion of a 4-week
course of rituximab therapy

- No uncontrolled psychiatric illness or medical condition that would preclude
tolerance of study treatment

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- Recovered from prior therapy for at least 7 days

- More than 30 days since prior cytotoxic chemotherapy

- At least 14 days since prior steroids

- At least 14 days since prior radiotherapy to non-target lesions

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Toxicity as assessed by NCI CTCAE v3.0

Outcome Time Frame:

4 years

Safety Issue:

Yes

Principal Investigator

Roger Strair, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cancer Institute of New Jersey

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000540171

NCT ID:

NCT00176475

Start Date:

January 2005

Completion Date:

February 2008

Related Keywords:

  • Leukemia
  • Lymphoma
  • Multiple Myeloma and Plasma Cell Neoplasm
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • nodal marginal zone B-cell lymphoma
  • recurrent adult Burkitt lymphoma
  • recurrent adult diffuse large cell lymphoma
  • recurrent adult Hodgkin lymphoma
  • recurrent adult lymphoblastic lymphoma
  • recurrent adult acute lymphoblastic leukemia
  • refractory chronic lymphocytic leukemia
  • recurrent small lymphocytic lymphoma
  • refractory hairy cell leukemia
  • prolymphocytic leukemia
  • recurrent marginal zone lymphoma
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent grade 3 follicular lymphoma
  • refractory multiple myeloma
  • recurrent mantle cell lymphoma
  • recurrent adult grade III lymphomatoid granulomatosis
  • Waldenstrom macroglobulinemia
  • splenic marginal zone lymphoma
  • stage II multiple myeloma
  • stage III multiple myeloma
  • stage IV adult Burkitt lymphoma
  • stage IV adult diffuse large cell lymphoma
  • stage IV adult Hodgkin lymphoma
  • stage IV adult lymphoblastic lymphoma
  • stage III adult Burkitt lymphoma
  • stage III adult diffuse large cell lymphoma
  • stage III adult Hodgkin lymphoma
  • stage III adult lymphoblastic lymphoma
  • stage III grade 1 follicular lymphoma
  • stage III grade 2 follicular lymphoma
  • stage III grade 3 follicular lymphoma
  • stage IV grade 1 follicular lymphoma
  • stage IV grade 2 follicular lymphoma
  • stage IV grade 3 follicular lymphoma
  • stage III mantle cell lymphoma
  • stage IV mantle cell lymphoma
  • stage III marginal zone lymphoma
  • stage IV marginal zone lymphoma
  • stage III small lymphocytic lymphoma
  • stage IV small lymphocytic lymphoma
  • stage III chronic lymphocytic leukemia
  • stage IV chronic lymphocytic leukemia
  • progressive hairy cell leukemia, initial treatment
  • Neoplasms
  • Leukemia
  • Lymphoma
  • Lymphoproliferative Disorders
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma

Name

Location

Cancer Institute of New Jersey at HamiltonHamilton, New Jersey  08690
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical SchoolNew Brunswick, New Jersey  08903