A Study of Venetoclax in Combination With Navitoclax and Chemotherapy in Subjects With Relapsed/Refractory Acute Lymphoblastic Leukemia or Relapsed/Refractory Lymphoblastic Lymphoma

Study Description

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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 Design

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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

Arms and Interventions

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Arm

Intervention/treatment

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.

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

Outcome Measures

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Primary Outcome Measures :

1. Cmax of Venetoclax + Navitoclax [ Time Frame: Up to approximately 9 months ]
   Maximum observed plasma concentration (Cmax) of venetoclax + navitoclax
2. AUC of Venetoclax + Navitoclax [ Time Frame: Up to approximately 9 months ]
   Area under the plasma concentration-time curve (AUC) of venetoclax + navitoclax
3. Tmax of Venetoclax + Navitoclax [ Time Frame: Up to approximately 9 months ]
   Time to Cmax (Tmax) of Venetoclax + Navitoclax
4. CL/F of Venetoclax + Navitoclax [ Time Frame: Up to approximately 9 months ]
   Apparent oral clearance (CL/F) of venetoclax + navitoclax
5. Number of participants with dose-limiting toxicities (DLT) [ Time Frame: Up to approximately 28 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 :

1. 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.
2. 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.
3. Number of Participant who Proceed to Stem Cell Transplantation or Chimeric antigen receptor T-cell (CAR-T) Therapy [ 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 or CAR-T therapy.
4. 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.
5. 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.
6. 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.

Eligibility Criteria

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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:

• 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.

• 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 central nervous system (CNS) disease with cranial involvement that requires radiation.
• 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.

• 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

    • Exception: Philadelphia Chromosome (Ph)+ ALL subjects on TKIs at Screening may enroll and remain on Tyrosine Kinase Inhibitor (TKI) therapy to control disease
  • 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 excluded 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.

Contacts and Locations

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Contacts

Contact: ABBVIE CALL CENTER	847.283.8955	abbvieclinicaltrials@abbvie.com

Locations

United States, California
City of Hope /ID# 169029	Recruiting
Duarte, California, United States, 91010
LPCH Stanford /ID# 163337	Recruiting
Palo Alto, California, United States, 94304
United States, Illinois
University of Chicago /ID# 163369	Recruiting
Chicago, Illinois, United States, 60637
United States, Missouri
Washington University-School of Medicine /ID# 165689	Recruiting
Saint Louis, Missouri, United States, 63110
United States, North Carolina
Univ NC Chapel Hill /ID# 163509	Recruiting
Chapel Hill, North Carolina, United States, 27514-4220
United States, Ohio
Cincinnati Children's Hospital /ID# 164619	Recruiting
Cincinnati, Ohio, United States, 45229
Nationwide Childrens Hospital /ID# 163372	Recruiting
Columbus, Ohio, United States, 43205
United States, Oregon
Oregon Health and Science University /ID# 165690	Recruiting
Portland, Oregon, United States, 97239-3098
United States, Tennessee
St. Jude Childrens Res Hosp /ID# 163335	Recruiting
Memphis, Tennessee, United States, 38105
United States, Texas
UT Southwestern Medical Center /ID# 163346	Recruiting
Dallas, Texas, United States, 75390-7208
MD Anderson Cancer Center /ID# 163327	Recruiting
Houston, Texas, United States, 77030
United States, Wisconsin
University of Wisconsin-Madiso /ID# 165691	Recruiting
Madison, Wisconsin, United States, 53705
Australia, Victoria
Alfred Hospital /ID# 169576	Not yet recruiting
Melbourne, Victoria, Australia, 3004
Victorian Comprehensive Cancer /ID# 165710	Recruiting
Melbourne, Victoria, Australia, 3050
Royal Children's Hospital /ID# 163322	Recruiting
Melbourne, Victoria, Australia, 3052

Sponsors and Collaborators

AbbVie

Investigators

Study Director:	AbbVie Inc.	AbbVie

More Information

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Additional Information:

Related Info 

Responsible Party:	AbbVie
ClinicalTrials.gov Identifier:	NCT03181126 History of Changes
Other Study ID Numbers:	M16-106
First Posted:	June 8, 2017
Last Update Posted:	November 12, 2018
Last Verified:	October 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:

Relapsed of Refractory Acute Lymphoblastic Leukemia; Cancer; Venetoclax; Navitoclax

Additional relevant MeSH terms:

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