Clinical Trial: NCT02483000 - My Cancer Genome

NCT02483000

Description:

This phase I/II trial studies the side effects and best dose of anti-cluster of differentiation (CD)20 radioimmunotherapy (RIT), and to see how well it works when given before chemotherapy and stem cell transplant in treating patients with B-cell malignancies that have not responded to treatment or have come back after responding to treatment. CD20 is a protein found on the cells of a type of cancer cell called B-cells. Anti-CD20 RIT attaches radioactive material to a drug that is designed to target CD20, which brings radioactive material to the cancer cells to kill the cells. This may kill more tumor cells while causing fewer side effects to healthy tissue. Adding anti-CD20 to standard chemotherapy and stem cell transplant may be more effective in treating patients with B-cell malignancies.

Related Conditions:

Lymphoma

Recruiting Status:

Terminated

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT02483000

Trial Eligibility

Document

Title

Brief Title: Anti-CD20 Radioimmunotherapy Before Chemotherapy and Stem Cell Transplant in Treating Patients With High-Risk B-Cell Malignancies
Official Title: Evaluation of Pretargeted Anti-CD20 Radioimmunotherapy Combined With BEAM Chemotherapy and Autologous Stem Cell Transplantation for High-Risk B-Cell Malignancies

Clinical Trial IDs

ORG STUDY ID: 9189
SECONDARY ID: NCI-2015-00299
SECONDARY ID: 9189
SECONDARY ID: P01CA044991
SECONDARY ID: P30CA015704
NCT ID: NCT02483000

Conditions

Burkitt Lymphoma
CD20-Positive Neoplastic Cells Present
Diffuse Large B-Cell Lymphoma
Indolent Non-Hodgkin Lymphoma
Mantle Cell Lymphoma
Recurrent B-Cell Non-Hodgkin Lymphoma
Refractory Mature B-Cell Non-Hodgkin Lymphoma

Interventions

Drug	Synonyms	Arms
Anti-CD20 B9E9 scFv-Streptavidin Fusion Protein	Anti-CD20 B9E9 scFv-SA Fusion Protein, Anti-CD20 B9E9-SA Fusion Protein, B9E9 scFvSA Fusion Protein, Recombinant Anti-CD20 B9E9 scFvSA Fusion Protein, scFv B9E9-streptavidin Fusion Protein	Treatment (PRIT)
Carmustine	BCNU, Becenum, Becenun, BiCNU, Bis(chloroethyl) Nitrosourea, Bis-Chloronitrosourea, Carmubris, Carmustin, Carmustinum, FDA 0345, Gliadel, N,N'-Bis(2-chloroethyl)-N-nitrosourea, Nitrourean, Nitrumon, SK 27702, SRI 1720, WR-139021	Treatment (PRIT)
Clearing Agent		Treatment (PRIT)
Cytarabine	.beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosar-U, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453	Treatment (PRIT)
Etoposide	Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16-213, VP-16, VP-16-213	Treatment (PRIT)
Melphalan	Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard, L-Sarcolysin, L-Sarcolysin Phenylalanine mustard, L-Sarcolysine, Melphalanum, Phenylalanine Mustard, Phenylalanine Nitrogen Mustard, Sarcoclorin, Sarkolysin, WR-19813	Treatment (PRIT)

Purpose

Detailed Description

      PRIMARY OBJECTIVES:

      I. To estimate the maximum tolerated dose (MTD) of 90Y activity that can be delivered via
      pretargeted radioimmunotherapy (PRIT) using B9E9-fusion protein (B9E9-FP), clearing agent
      (CA), and radiolabeled tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-biotin when
      followed by carmustine, etoposide, cytarabine, and melphalan (BEAM) chemotherapy and
      autologous stem cell transplantation.

      SECONDARY OBJECTIVES:

      I. To assess the overall and progression-free survival of the above regimen in such patients.

      II. To evaluate the response rates of the above therapy.

      III. To evaluate the toxicity and tolerability of the above therapy.

      IV. To evaluate the feasibility of delivering sequential high-dose PRIT and chemotherapy.

      TERTIARY OBJECTIVES:

      I. Assess biodistribution and pharmacokinetics of B9E9-FP and radiolabeled DOTA-Biotin.

      II. Assess ability of the clearing agent (CA) to remove excess B9E9-FP from the serum.

      III. Evaluate the impact, if any, of circulating rituximab on biodistributions.

      OUTLINE: This is a phase I, dose-escalation study of yttrium Y 90 DOTA-biotin followed by a
      phase II study.

      B9E9-FP INFUSION: Patients receive B9E9-fusion protein intravenously (IV) over a minimum of 2
      hours on day -17.

      CLEARING AGENT INFUSION: Patients receive clearing agent IV over a minimum of 30 minutes on
      day -15.

      RADIOBIOTIN INFUSION: Patients receive indium In 111-DOTA-biotin IV and yttrium Y 90
      DOTA-biotin IV over 2-5 minutes on day -14.

      BEAM CHEMOTHERAPY: Patients receive BEAM chemotherapy comprising carmustine IV over 3 hours
      on day -7; etoposide IV over 2 hours twice daily (BID) and cytarabine IV over 4 hours BID on
      days -6 to -3; and melphalan IV over 30 minutes on day -2.

      STEM CELL INFUSION: Patients undergo autologous peripheral blood stem cell transplant (PBSCT)
      on day 0 per standard of care.

      After completion of study treatment, patients are followed up at 1, 3, 6, and 12 months, and
      then annually thereafter.

Trial Arms

Name	Type	Description	Interventions
Treatment (PRIT)	Experimental	B9E9-FP INFUSION: Patients receive B9E9-fusion protein IV over a minimum of 2 hours on day -17. CLEARING AGENT INFUSION: Patients receive clearing agent IV over a minimum of 30 minutes on day -15. RADIOBIOTIN INFUSION: Patients receive indium In 111-DOTA-biotin IV and yttrium Y 90 DOTA-biotin IV over 2-5 minutes on day -14. BEAM CHEMOTHERAPY: Patients receive BEAM chemotherapy comprising carmustine IV over 3 hours on day -7; etoposide IV over 2 hours BID and cytarabine IV over 4 hours BID on days -6 to -3; and melphalan IV over 30 minutes on day -2. STEM CELL INFUSION: Patients undergo autologous PBSCT on day 0 per standard of care.	Anti-CD20 B9E9 scFv-Streptavidin Fusion Protein Carmustine Clearing Agent Cytarabine Etoposide Melphalan

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have a histologically confirmed diagnosis of lymphoma expressing the
             CD20 antigen and generally must have failed at least one prior standard systemic
             therapy; the exception will be mantle cell lymphoma (MCL) patients, who may be
             enrolled while in first complete remission (CR) as well as other select high-risk
             lymphomas (e.g., Burkitt?s, double hit diffuse large B-cell lymphoma [DLBCL],
             transformed indolent B-cell non-Hodgkin lymphoma [B-NHL], etc.) in accordance with
             current transplant standard of care for these patients

          -  Creatinine (Cr) < 2.0

          -  Bilirubin < 1.5 mg/dL, with the exception of patients thought to have Gilbert?s
             syndrome, who may have a total bilirubin above 1.5 mg/dL

          -  All patients eligible for therapeutic study must have (>= 2 x 10^6 CD34/kg) autologous
             hematopoietic stem cells harvested and cryopreserved

          -  Patients must have an expected survival of > 60 days and must be free of major
             infection

          -  Patients of childbearing potential must agree to abstinence or the use of effective
             contraception

          -  DONOR SELECTION: Not applicable; this protocol employs autologous transplantation,
             utilizing the patient?s own hematopoietic stem cells obtained from either the
             peripheral blood or bone marrow

        Exclusion Criteria:

          -  Systemic anti-lymphoma therapy given in the previous 30 days before the scheduled 90Y
             therapy dose

          -  Inability to understand or give an informed consent

          -  Prior radiation > 20 Gy to any critical normal organ (e.g., lung, liver, spinal cord,
             both kidneys) within 1 year of the treatment date

          -  Active central nervous system lymphoma

          -  Other serious medical conditions considered to represent contraindications to bone
             marrow transplant (BMT) (e.g., abnormally decreased cardiac ejection fraction,
             diffusion capacity of the lung for carbon monoxide [DLCO] < 50% predicted, patient on
             supplemental oxygen, acquired immune deficiency syndrome [AIDS], etc.)

          -  Pregnancy or breast feeding

          -  Prior bone marrow or stem cell transplant

          -  Southwest Oncology Group (SWOG) performance status >= 2.0

          -  Known sensitivity to kanamycin and other aminoglycosides; patients with known
             hypersensitivity to kanamycin or any other aminoglycoside antibiotic will be excluded

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Maximum Tolerated Dose (MTD) of Yttrium Y 90 DOTA-biotin Defined as the Dose That is Associated With a True Dose Limiting Toxicity (DLT) Rate of 25%, Where a DLT is Defined as a Therapy-related Grade III or IV Bearman (Transplant) Toxicity
Time Frame:	Up to 30 days after transplant
Safety Issue:
Description:	Following the completed observation of the final patient, a two-parameter logistic model will be fit to the data, thereby generating a dose-toxicity curve based on the observed DLT rate at the various dose levels visited. Based on this fitted model, the MTD is estimated to be the dose that is associated with a DLT rate of 25%.

Secondary Outcome Measures

Measure:	Dosimetry of Yttrium Y 90 DOTA-biotin
Time Frame:	Up to 7 days after infusion
Safety Issue:
Description:	Assessed using OLINDA dosimetry software. The estimated dose to normal organs and tumor sites will be described based on the tumor to normal organ ratios derived from dosimetry estimates coupled with the absorbed dose to normal organs based on the administered activity of yttrium Y 90 DOTA-biotin.

Measure:	Incidence of Toxicity, Defined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Time Frame:	Up to 30 days after transplant
Safety Issue:
Description:	Descriptive statistics on the number and percent toxicities will be calculated.

Measure:	Overall Response Rate
Time Frame:	Up to 4 years
Safety Issue:
Description:	Descriptive statistics on the responses will be calculated.

Measure:	Overall Survival
Time Frame:	Up to 4 years
Safety Issue:
Description:	Overall survival will be estimated.

Measure:	Progression Free Survival (PFS)
Time Frame:	1 year from autologous stem cell transplant
Safety Issue:
Description:	If the true 1-year PFS rate using the proposed approach is 54%, then 24 patients will provide 80% power to detect a statistically significant increased rate of PFS from the fixed rate of 30%, based on a one-sample chi-square test with one-sided significance level of 5%.

Details

Phase:	Phase 1
Primary Purpose:	Interventional
Overall Status:	Terminated
Lead Sponsor:	Fred Hutchinson Cancer Research Center

Last Updated

November 23, 2020

Clinical Trials /

Anti-CD20 Radioimmunotherapy Before Chemotherapy and Stem Cell Transplant in Treating Patients With High-Risk B-Cell Malignancies