Immunotoxin Therapy and Cytarabine in Treating Patients With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia
A Phase 1 Study of the Deglycosylated Ricin A Chain-containing Combined Anti-CD19 and Anti-CD22 Immunotoxin Combotox in Combination With High-Dose Cytarabine in Adult Relapsed or Refractory B-lineage Acute Lymphoblastic Leukemia
4 other identifiers
interventional
18
1 country
2
Brief Summary
This phase I trial studies the side effects and the best dose of deglycosylated ricin A chain-conjugated anti-cluster of differentiation (CD)19/anti-CD22 immunotoxins when given together with cytarabine in treating patients with B-cell acute lymphoblastic leukemia that has come back after a period of improvement (relapsed) or does not respond to treatment (refractory). Immunotoxins, such as deglycosylated ricin A chain-conjugated anti-CD19/anti-CD22 immunotoxins, can find certain cancer cells and kill them without harming normal cells. Drugs used in chemotherapy, such as cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving deglycosylated ricin A chain-conjugated anti-CD19/anti-CD22 immunotoxins with cytarabine may kill more cancer cells.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Apr 2013
Longer than P75 for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 12, 2011
CompletedFirst Posted
Study publicly available on registry
August 3, 2011
CompletedStudy Start
First participant enrolled
April 1, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 26, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
June 26, 2018
CompletedSeptember 6, 2019
September 1, 2019
5.2 years
July 12, 2011
September 4, 2019
Conditions
Outcome Measures
Primary Outcomes (1)
Occurrence of dose-limiting toxicity, defined as grade 3 or greater non-hematological adverse event attributable to Combotox, graded per the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Up to 28 days
Secondary Outcomes (1)
Clinical response rate (response defined as complete response or partial response)
Up to day 42
Other Outcomes (6)
Change in expression of CD19 and CD22 on cell surface by flow cytometry
Baseline to up to day 42
Change in fractional excretion of urinary sodium (FeNa)
Day 0 to up to day 12
Development of VLS
Up to day 12
- +3 more other outcomes
Study Arms (1)
Treatment (Combotox, cytarabine)
EXPERIMENTALPatients receive high-dose cytarabine IV over 2-3 hours every 12 hours on days 1-3 and deglycosylated ricin A chain-conjugated anti-CD19/anti-CD22 immunotoxins IV over 4 hours on days 8, 10, and 12. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Interventions
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- Patients must have histologically confirmed B-lineage acute lymphoblastic leukemia (ALL) at diagnosis and either evidence of relapse/refractory disease based on a bone marrow/peripheral blood examination or evidence by cytogenetic studies or polymerase chain reaction (PCR) amplification; patients with only extramedullary disease in the absence of bone marrow or blood involvement are not eligible; patients with L3 (Burkitt's) are not eligible; for ALL in marrow or peripheral blood, immunophenotyping of the blood or marrow lymphoblasts must be performed to determine lineage (B cell, T-cell, or mixed B/T cell); NOTE: appropriate marker studies including CD19 (B cell), CD10, CD5, and CD7 (T cell) must be performed; co-expression of myeloid antigens (CD13 and CD33) will not exclude patients; if possible, the lineage specific markers cytoplasmic CD22 or CD79a (B cells), cytoplasmic CD3 (T cells) and cytoplasmic myeloperoxidase (MPO) (myeloid cells) must be determined; patients with mixed lineage ALL (ML-ALL) as defined by a lack of cytochemical markers of myeloid differentiation, and by the presence of immunophenotypic markers suggesting both lymphoid and myeloid differentiation, are allowed
- CD19 and/or CD22 must be expressed on at least 50% of the lymphoblasts
- Disease must be refractory to conventional induction therapy or relapsed after initial standard therapy for ALL; any number of prior therapies is permitted and including allogeneic and/or autologous stem cell transplant
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
- Life expectancy of greater than 2 months
- Total bilirubin =\< 1.5 x institutional upper limit of normal, unless related to leukemic infiltration or hemolysis
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal, unless related to leukemic infiltration or hemolysis
- Creatinine within normal institutional limits OR
- Creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
- Patients must have recovered from effects of prior therapy; at least 2 weeks should have elapsed since the last dose of high dose chemotherapy; hydroxyurea, steroids and vincristine are allowed to control counts until eligibility is confirmed and study treatment can be initiated
- Adequate cardiac function defined as an ejection fraction of \>= 50% by multi gated acquisition scan (MUGA) scan or echocardiogram and a corrected QT (QTc) interval of =\< 450 ms for men and =\< 460 ms for women
- Adequate pulmonary function defined as no evidence of dyspnea at rest
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Ability to understand and the willingness to sign a written informed consent document
You may not qualify if:
- Patients who have had chemotherapy or radiotherapy within 2 weeks (4 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier
- Patients may not be receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to Combotox or other agents used in study agents
- Presence of a significant pleural effusion by chest x-ray
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic
- Presence of active untreated central nervous system (CNS) leukemia
- Presence of graft-versus-host disease (GVHD) more than grade 2
- History of documented seizure disorder, presence of cerebellar dysfunction, dysphasia or altered mental status on neurological examination
- Human anti-mouse antibody (HAMA) levels of \> 100 ug/ml or human ricin antibodies (HARA) \> 100 ug/ml HARA after cycle 1
- Impaired liver function defined as a total bilirubin \> 1.5 x normal range and AST or ALT \> 2.5 x normal range unless secondary to Gilbert's disease, hemolysis or leukemic involvement of the liver
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with Combotox
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
Albert Einstein College of Medicine
The Bronx, New York, 10461, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111, United States
Related Publications (1)
Barta SK, Zou Y, Schindler J, Shenoy N, Bhagat TD, Steidl U, Verma A. Synergy of sequential administration of a deglycosylated ricin A chain-containing combined anti-CD19 and anti-CD22 immunotoxin (Combotox) and cytarabine in a murine model of advanced acute lymphoblastic leukemia. Leuk Lymphoma. 2012 Oct;53(10):1999-2003. doi: 10.3109/10428194.2012.679267. Epub 2012 Apr 18.
PMID: 22448921DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Amit Verma
Albert Einstein College of Medicine
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
July 12, 2011
First Posted
August 3, 2011
Study Start
April 1, 2013
Primary Completion
June 26, 2018
Study Completion
June 26, 2018
Last Updated
September 6, 2019
Record last verified: 2019-09