A Study of Venetoclax in Combination With Navitoclax and Chemotherapy in Subjects With Relapsed Acute Lymphoblastic Leukemia or Relapsed/Refractory Lymphoblastic Lymphoma
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| ClinicalTrials.gov Identifier: NCT03181126 |
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Recruitment Status :
Recruiting
First Posted : June 8, 2017
Last Update Posted : June 14, 2018
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Sponsor:
AbbVie
Information provided by (Responsible Party):
AbbVie
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Brief Summary:
This dose-escalating study is to determine the safety, pharmacokinetics, and preliminary efficacy of venetoclax in combination with navitoclax and chemotherapy in adult and pediatric participants with relapsed/refractory acute lymphoblastic leukemia (ALL) or relapsed/refractory lymphoblastic lymphoma.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Acute Lymphoblastic Leukemia (ALL) Lymphoblastic Lymphoma | Drug: Navitoclax Drug: Chemotherapy Drug: Venetoclax | Phase 1 |
Expanded Access : An investigational treatment associated with this study is available outside the clinical trial. More info ...
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 42 participants |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 1 Dose Escalation, Open-Label Study of Venetoclax in Combination With Navitoclax and Chemotherapy in Subjects With Relapsed/Refractory Acute Lymphoblastic Leukemia or Relapsed/Refractory Lymphoblastic Lymphoma |
| Actual Study Start Date : | November 28, 2017 |
| Estimated Primary Completion Date : | March 7, 2020 |
| Estimated Study Completion Date : | June 17, 2020 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Venetoclax
| Arm | Intervention/treatment |
|---|---|
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Experimental: Venetoclax + Navitoclax + Chemotherapy
Venetoclax weight-adjusted doses administered orally every day (QD) starting on Day 1 + navitoclax various, weight-adjusted doses administered orally QD starting on Day 3 + chemotherapy (peg-asparaginase [or any other forms of asparaginase], vincristine, dexamethasone) and tyrosine kinase inhibitor [TKI, if applicable]). This regimen and any of its components may be delayed, reduced or omitted at the discretion of the Investigator.
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Drug: Navitoclax
tablet
Other Name: ABT-263 Drug: Chemotherapy peg-asparaginase (or other form of asparaginase, per local standard of care (intravenous) + vincristine (intravenous) + dexamethasone (oral) + tyrosine kinase inhibitor (TKI) (if applicable, oral) Drug: Venetoclax tablet
Other Name: ABT-199 GDC-0199 |
Primary Outcome Measures :
- Cmax of Venetoclax + Navitoclax [ Time Frame: Up to approximately 9 months ]Maximum observed plasma concentration (Cmax) of venetoclax + navitoclax
- AUC of Venetoclax + Navitoclax [ Time Frame: Up to approximately 9 months ]Area under the plasma concentration-time curve (AUC) of venetoclax + navitoclax
- Tmax of Venetoclax + Navitoclax [ Time Frame: Up to approximately 9 months ]Time to Cmax (Tmax) of Venetoclax + Navitoclax
- CL/F of Venetoclax + Navitoclax [ Time Frame: Up to approximately 9 months ]Apparent oral clearance (CL/F) of venetoclax + navitoclax
- Number of participants with dose-limiting toxicities (DLT) [ Time Frame: Up to approximately 35 days after initial dose of study drug ]A DLT is any Grade 3 or higher non-hematologic adverse event (AE) with exceptions outlined in the protocol. AEs and toxicities that occur beyond the DLT assessment period will also be evaluated by the investigator and AbbVie and may be considered as dose-limiting.
Secondary Outcome Measures :
- Progression-free survival (PFS) [ Time Frame: Up to 9 months after the last subject has enrolled into the study ]PFS is defined as the number of days from the date of enrollment to the date of earliest disease progression or death.
- Partial Response (PR) rate [ Time Frame: Up to 9 months after the last subject has enrolled into the study ]PR defined as no peripheral blasts or peripheral blood absolute blast count decreased by ≥ 50% from baseline, bone marrow with 5 - 25% blasts and at least a 50% decrease in bone marrow blast percent from baseline, no evidence of extramedullary disease.
- Number of Participant who Proceed to Stem Cell Transplantation [ Time Frame: Up to 9 months after the last subject has enrolled into the study ]Determine the number of participants who proceed to stem cell transplantation.
- Overall survival (OS) [ Time Frame: Up to 9 months after the last subject has enrolled into the study ]OS is defined as the number of days from the date of enrollment to the date of death.
- Objective response rate (ORR) [ Time Frame: Up to 9 months after the last subject has enrolled into the study ]The proportion of subjects with objective response rate (complete response [CR] + CR incomplete recovery [CRi] + CR without platelet recovery [CRp]) for ALL subjects and (CR+PR) for LL subjects.
- Complete Response (CR) rate [ Time Frame: Up to 9 months after the last subject has enrolled into the study ]CR defined as hematologic recovery (absolute neutrophil count [ANC] greater than or equal to 500/μL; platelet counts greater than or equal to 75,000/μL), evidence of trilineage hematopoiesis in the bone marrow and less than 5% blasts in the bone marrow, absence of circulating blasts, and no evidence of extramedullary disease.
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| Ages Eligible for Study: | 4 Years and older (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
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Must have relapsed or refractory acute lymphoblastic leukemia (ALL) or relapsed or refractory lymphoblastic lymphoma (LL). Refractory is defined as persistent disease after at least 2 courses of chemotherapy.
- Participants with ALL with Philadelphia chromosome or with an ABL class targetable fusion are eligible.
- Participants with LL must have radiographic evidence of disease
- Must weigh greater than or equal to 20 kg.
- Must be able to swallow pills.
- Must have adequate hepatic and kidney function.
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Must have adequate performance status:
- Participants less than or equal to 16 years of age: Lansky greater than or equal to 50
- Participants greater than 16 years of age: Karnofsky greater than or equal to 50 or Eastern Cooperative Oncology Group (ECOG) less than 3.
Exclusion Criteria:
- Participant has overt central nervous system (CNS) disease (CNS 3 status)
- Participants who are less than 100 days post-transplant, or greater than 100 days post-transplant with active graft versus host disease (GVHD), or are still continuing post-transplant immunosuppressant therapy within 7 days prior to the first dose of study drug.
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Participants who have received any of the following prior to the first dose of study drug:
- Inotuzumab within 30 days and must have ALT, AST and bilirubin < ULN.
- A biologic agent (i.e., monoclonal antibodies) for anti-neoplastic intent within 30 days
- CAR-T infusion or other cellular therapy within 30 days
- any anti-cancer therapy including blinatumomab, chemotherapy, radiation therapy targeted small molecule agents or investigational agents within 14 days, or 5 half-lives, whichever is shorter
- Steroid therapy for anti-neoplastic intent within 5 days
- Hydroxyurea that is ongoing (hydroxyurea is permitted up to the first dose)
- A strong or moderate CYP3A inhibitor or inducer within 7 days
- Aspirin within 7 days, or 5 half-lives, whichever is longer
- An antiplatelet/anticoagulant drug or a herbal supplement that affects platelet function within 7 days, or 5 half-lives, whichever is longer
- Participants with malabsorption syndrome or any other condition that precludes enteral administration.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03181126
Contacts
| Contact: ABBVIE CALL CENTER | 847.283.8955 | abbvieclinicaltrials@abbvie.com |
Locations
| United States, California | |
| City of Hope | Recruiting |
| Duarte, California, United States, 91010 | |
| LPCH Stanford | Recruiting |
| Palo Alto, California, United States, 94304 | |
| United States, Illinois | |
| University of Chicago | Recruiting |
| Chicago, Illinois, United States, 60637 | |
| United States, Missouri | |
| Washington University-School of Medicine | Recruiting |
| Saint Louis, Missouri, United States, 63110 | |
| United States, North Carolina | |
| Univ NC Chapel Hill | Recruiting |
| Chapel Hill, North Carolina, United States, 27514-4220 | |
| United States, Ohio | |
| Cincinnati Children's Hospital | Recruiting |
| Cincinnati, Ohio, United States, 45229 | |
| Nationwide Childrens Hospital | Recruiting |
| Columbus, Ohio, United States, 43205 | |
| United States, Oregon | |
| Oregon Health and Science University | Recruiting |
| Portland, Oregon, United States, 97239-3098 | |
| United States, Tennessee | |
| St. Jude Childrens Res Hosp | Recruiting |
| Memphis, Tennessee, United States, 38105 | |
| United States, Texas | |
| UT Southwestern Medical Center | Recruiting |
| Dallas, Texas, United States, 75390-7208 | |
| MD Anderson Cancer Center | Recruiting |
| Houston, Texas, United States, 77030 | |
| United States, Wisconsin | |
| University of Wisconsin-Madiso | Not yet recruiting |
| Madison, Wisconsin, United States, 53705 | |
| Australia, Victoria | |
| Alfred Hospital | Not yet recruiting |
| Melbourne, Victoria, Australia, 3004 | |
| Victorian Comprehensive Cancer | Recruiting |
| Melbourne, Victoria, Australia, 3050 | |
| Royal Children's Hospital | Not yet recruiting |
| Melbourne, Victoria, Australia, 3052 | |
Sponsors and Collaborators
AbbVie
Investigators
| Study Director: | AbbVie Inc. | AbbVie |
Additional Information:
| Responsible Party: | AbbVie |
| ClinicalTrials.gov Identifier: | NCT03181126 History of Changes |
| Other Study ID Numbers: |
M16-106 |
| First Posted: | June 8, 2017 Key Record Dates |
| Last Update Posted: | June 14, 2018 |
| Last Verified: | June 2018 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| Studies a U.S. FDA-regulated Drug Product: | Yes | |
| Studies a U.S. FDA-regulated Device Product: | No | |
| Product Manufactured in and Exported from the U.S.: | No | |
Keywords provided by AbbVie:
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Relapsed of Refractory Acute Lymphoblastic Leukemia Cancer Venetoclax Navitoclax |
Additional relevant MeSH terms:
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Lymphoma Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Lymphoma, Non-Hodgkin Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders |
Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Venetoclax Navitoclax Asparaginase Antineoplastic Agents |