Phase I/II Study of Yttrium-90 Labeled Anti-CD25 (a-Tac) Monoclonal Antibody Plus BEAM for Autologous Hematopoietic Cell Transplantation (AHCT) in Patients With Primary Refractory or Relapsed Hodgkin Lymphoma, the "a-Tac BEAM Regimen"
18 Years
70 Years
Both
Recurrent Adult Hodgkin Lymphoma
Trial Information
Phase I/II Study of Yttrium-90 Labeled Anti-CD25 (a-Tac) Monoclonal Antibody Plus BEAM for Autologous Hematopoietic Cell Transplantation (AHCT) in Patients With Primary Refractory or Relapsed Hodgkin Lymphoma, the "a-Tac BEAM Regimen"
OBJECTIVES:
I. To determine the safety and feasibility of the autologous hematopoietic cell
transplantation (AHCT) regimen of Yttrium-90 (90Y) labeled anti-CD25 monoclonal antibody
(basiliximab), given in combination with standard dose(s) of BEAM in patients with primary
progressive or relapsed Hodgkin lymphoma (HL).
(Phase I) II. To determine the phase II dose (P2D) and characterize toxicities at each dose
level -including time course.
(Phase I) III. To evaluate hematological recovery in terms of neutrophil and platelet
engraftment time.
(Phase I) IV. To estimate the radiation doses to the whole body and normal organs through
serial imaging studies.
(Phase I) V. To define biodistribution/extended pharmacokinetics of 111Indium
(In)-basiliximab and 90Y- basiliximab including terminal elimination, serum half-life
(t1/2), and area under the curve (AUC).
(Phase I) VI. Using the P2D defined in the Phase I study, to determine anti-tumor activity
of anti (a)Tac-BEAM as assessed by progression-free survival (PFS).
(Phase II) VII. To determine the overall response rate (ORR: complete remission [CR] +
partial remission [PR]) and response duration.
(Phase II) VIII. To estimate the overall survival, and non-relapse mortality (NRM) at
100-days and 1-year.
(Phase II) IX. To summarize toxicities by organ and severity, evaluating short and long-term
complications, including, delayed engraftment, infection, and myelodysplasia.
(Phase II) X. To descriptively compare the outcomes of patients treated on this protocol to
a comparable patient population treated with conventional BEAM for relapsed and refractory
HL.
(Phase II) OUTLINE: DOSIMETRY STUDY: Patients receive basiliximab intravenously (IV) and
indium In 111 basiliximab IV on day -21. Patients undergo indium In 111 imaging scans daily.
Patients with appropriate biodistribution continue on to treatment.
TREATMENT: Patients receive basiliximab IV and yttrium Y 90 basiliximab IV on day -14.
Patients also receive BEAM chemotherapy comprising carmustine IV over 2 hours on days -7 and
-6, etoposide IV over 4 hours and cytarabine IV over 2 hours twice daily (BID) on days -5 to
-2, and melphalan IV on day -1. Patients undergo autologous hematopoietic progenitor cell
infusion on day 0.
After completion of study treatment, patients are followed up at day 90-100, 180, 1 year,
1.5 years, and 2-5 years.
Inclusion Criteria:
- Pathology confirmation of HL with City of Hope (COH) pathology review; the COH
Department of Pathology will stain the biopsy tissue for CD25 and will
semiquantitatively score the expression of CD25 on the HL cells (neoplastic cells)
and surrounding lymphocytes, since this may correlate with the response to treatment
- Hodgkin Lymphoma that is:
- Primary Induction Failure-resistant (PIF res): Never in complete remission but
with stable or progressive disease on treatment (primary refractory = PIF res)
- Primary Induction Failure-sensitive (PIF sen)/first partial remission (PR1) :
Never in complete remission, but with partial remission on treatment
- Early 1st relapse: Initial CR of > 3 months and < 12 months after 1st line
chemotherapy
- 1st relapsed HL in a patient who is not in CR after 2 cycles of salvage therapy
- In 2nd or subsequent RL whether in CR or not after salvage therapy
- Relapse/persistent disease evidenced by a computed tomography and
fluorodeoxyglucose-positron emission tomography (FDG-PET), or bone marrow biopsy
- Cardiac Ejection Fraction of > 50% by echocardiogram or MUGA
- Forced expiratory volume in one second (FEV1) > 65% of predicted measured, or
diffusion capacity of the lung for carbon monoxide (DLCO) >= 50% of predicted
measured
- Bilirubin =< 1.5 x normal
- Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvate
transaminase (SGPT) =< 2 x normal except in cases where abnormal liver function tests
(LFTS) are due to involvement with HL
- Serum creatinine of =< 1.5 mg/dL, and a measured creatinine clearance of >= 60 mL/min
- Karnofsky status >= 70%
- Life expectancy >= 6 months
- Females must not be pregnant or breast feeding, and must use accepted birth control
methods; males must use accepted birth control methods
- Capability of providing informed consent
- Patients will be enrolled after receiving at least two cycles of salvage
cytoreductive chemotherapy and collection of at least 3.0 x 10^6 CD34 cells/kg of
autologous hematopoietic progenitor cells (HPC-A) by apheresis; a minimum of 2
collection procedures is required; a maximum of 10 collections is allowed; bone
marrow harvest to supplement apheresis is not allowed
- Co-enrollment on institutional review board (IRB) #98117, entitled Molecular
Pathogenesis of Therapy-Related Leukemia, Dr. Bhatia, Principal Investigator
- Patient and insurer agree to have all pre-study and follow-up imaging studies
performed at City of Hope
- Recovery from non-hematologic toxicities of salvage cytoreductive chemotherapy to =<
grade 2 (CTCAE v4)
- Body mass index (BMI) > 30% will be considered on a case-by-case basis by the
Radiation Oncology Principal Investigator (P.I.)
Exclusion Criteria:
- Lymphocyte-predominant Hodgkin Lymphoma
- Prior high dose chemotherapy with autologous stem cell transplant, or prior
allogeneic transplantation
- Significant prior external beam dose-limiting radiation to a critical organ based on
review of the prior radiation treatment records by the Radiation Oncology PI;
patients who have had prior radiation to the lung will be excluded from the study,
although mediastinal irradiation will be permitted if minimal lung is in the
treatment volume; patients with > 500 cGy to the kidney will be excluded from the
study
- Presence of antibody against basiliximab
- Previous antibody based therapies
- Myelodysplasia or any active malignancy other than HL, or < 5 years remission from
any other prior malignancy, except adequately treated basal cell or squamous cell
carcinoma
- Active Hepatitis B or C viral infection or Hepatitis B surface antigen positive
- Positive Human Immunodeficiency Virus antibody
- Patients with psychosocial circumstances or illnesses that preclude protocol
participation (to be determined by P.I.)
- Co-morbid illnesses that preclude protocol participation (to be determined by PI)
- Abnormal marrow cytogenetics at any time, excluding proven constitutional cytogenetic
variants
- Persistent marrow involvement (> 10%) with HL after salvage cytoreductive therapy and
before stem cell mobilization
- Systemic chemotherapy or radiation within 4 weeks prior to the Y-90 dose of
radioimmunotherapy (RIT)
- Bone marrow (BM) harvest required to reach adequate cell dose for transplant
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
P2D of Yttrium-90 labeled basiliximab (phase I)
Outcome Description:
P2D is defined as the highest Yttrium-90 labeled basiliximab dose tested in which fewer than 33% of patients experience dose limiting toxicity (DLT) attributable to study treatment, among those evaluable for toxicity.
Outcome Time Frame:
Up to 18 months
Safety Issue:
Yes
Principal Investigator
Eileen Smith
Investigator Role:
Principal Investigator
Investigator Affiliation:
City of Hope Medical Center
Authority:
United States: Federal Government
Study ID:
08179
NCT ID:
NCT01476839
Start Date:
November 2012
Completion Date:
Related Keywords:
- Recurrent Adult Hodgkin Lymphoma
- Hodgkin Disease
- Lymphoma
Name | Location |
|---|---|
| City of Hope Medical Center | Duarte, California 91010 |
