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A Phase I Trial of a Combined Regimen of Chemotherapy and 90Y-Labeled, Humanized LL2 (Anti-CD22) Antibody With Peripheral Stem Cell Rescue for the Treatment of Relapsed or Refractory Non-Hodgkin's Lymphoma


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Leukemia, Lymphoma

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Trial Information

A Phase I Trial of a Combined Regimen of Chemotherapy and 90Y-Labeled, Humanized LL2 (Anti-CD22) Antibody With Peripheral Stem Cell Rescue for the Treatment of Relapsed or Refractory Non-Hodgkin's Lymphoma


OBJECTIVES: I. Determine the maximum tolerated dose and dose limiting toxicity of yttrium Y
90 humanized anti-CD22 LL2 (Y90 MOAB hLL2) in combination with salvage chemotherapy and
autologous peripheral blood stem cell rescue in patients with recurrent or refractory B-cell
malignancies. II. Study the effect of chemotherapy on the uptake of Y90 MOAB hLL2 into tumor
sites and normal organs by pretherapy imaging using indium In 111 humanized LL2 and
intratherapy imaging. III. Determine the extent and duration of tumor response in patients
receiving this regimen.

OUTLINE: This is a dose escalation study of yttrium Y 90 humanized anti-CD22 monoclonal
antibody LL2 (Y90 MOAB hLL2). Patients receive filgrastim (G-CSF) subcutaneously daily for 5
days and undergo harvest of peripheral blood stem cells (PBSC) on 2 or more consecutive
days. If an adequate number of CD34+ cells are not harvested, autologous bone marrow may be
used. Chemotherapy-induced mobilization with filgrastim allowed. Patients undergo pretherapy
imaging with indium In 111 humanized LL2 (In111 hLL2) for up to 40 minutes on day -7.
Patients receive Y90 MOAB hLL2 for up to 40 minutes on day 0 plus In111 hLL2, followed by
Y90 MOAB hLL2 alone on day 3. Patients receive ifosfamide IV over 1 hour, cisplatin IV over
2 hours, and cytarabine IV over 2 hours on days 1 and 4. Oral etoposide is given daily on
days 1-7. PBSC or bone marrow is reinfused on days 9-14, depending on MOAB clearance.
Cohorts of 3-6 patients receive escalating doses of Y90 MOAB hLL2 until the maximum
tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2
of 3 or 2 of 6 patients experience dose limiting toxicity. Patients are followed weekly for
2 months, monthly for 6 months, and then every 6 months for 5 years.

PROJECTED ACCRUAL: Approximately 15-24 patients will be accrued for this study within 2-2.5
years.

Inclusion Criteria


DISEASE CHARACTERISTICS: Histologically or cytologically confirmed recurrent or refractory
B-cell malignancy that has failed at least one standard therapy Stage II to IV
non-Hodgkin's lymphoma B-cell chronic lymphocytic leukemia, hairy cell leukemia, or
Waldenstrom's macroglobulinemia allowed if: Autologous bone marrow or peripheral blood
stem cells (PBSC) with no greater than 5% tumor involvement available Estimated radiation
dose to marrow no greater than 3,000 cGy (bone marrow involvement of greater than 25% is
allowed provided stem cell contamination and predicted marrow radiation doses are below
the above cited cut off values) At least 1 confirmed site of tumor targeted by pretherapy
indium In 111 humanized LL2 Autologous peripheral blood stem cells (PBSC) or bone marrow
available No active brain metastases

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Karnofsky 70-100%
Life expectancy: At least 3 months Hematopoietic: WBC at least 3,000/mm3 Granulocyte count
at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin less than 2
mg/dL Renal: Creatinine less than 1.5 times upper limit of normal Cardiovascular: Cardiac
ejection fraction greater than 50% Pulmonary: DLCO greater than 60% predicted Forced vital
capacity greater than 60% predicted Other: No severe anorexia, nausea, or vomiting HIV
negative No prisoners No concurrent significant medical complication that would preclude
study compliance Not pregnant Negative pregnancy test Fertile patients must use effective
contraception during and for 3 months after study

PRIOR CONCURRENT THERAPY: Biologic therapy: Prior low dose radioimmunotherapy allowed
Chemotherapy: No prior high dose chemotherapy with PBSC rescue At least 4 weeks since
prior chemotherapy and recovered Endocrine therapy: At least 2 weeks since prior
corticosteroids and recovered Radiotherapy: Prior low dose radioimmunotherapy allowed
Prior radiotherapy to less than 35% of red marrow allowed At least 4 weeks since prior
radiotherapy to index lesion Surgery: At least 4 weeks since major surgery

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Jack D. Burton, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Garden State Cancer Center at the Center for Molecular Medicine and Immunology

Authority:

United States: Federal Government

Study ID:

CDR0000067298

NCT ID:

NCT00004086

Start Date:

June 1997

Completion Date:

Related Keywords:

  • Leukemia
  • Lymphoma
  • Waldenstrom macroglobulinemia
  • refractory chronic lymphocytic leukemia
  • B-cell chronic lymphocytic leukemia
  • refractory hairy cell leukemia
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent grade 3 follicular lymphoma
  • recurrent adult diffuse small cleaved cell lymphoma
  • recurrent adult diffuse mixed cell lymphoma
  • recurrent adult diffuse large cell lymphoma
  • recurrent adult immunoblastic large cell lymphoma
  • recurrent adult lymphoblastic lymphoma
  • recurrent adult Burkitt lymphoma
  • recurrent mantle cell lymphoma
  • recurrent marginal zone lymphoma
  • recurrent small lymphocytic lymphoma
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • nodal marginal zone B-cell lymphoma
  • splenic marginal zone lymphoma
  • Leukemia
  • Lymphoma
  • Lymphoma, Non-Hodgkin

Name

Location

Garden State Cancer CenterBelleville, New Jersey  07103