Dose De-escalation Study of the PI3k Alpha/Delta Inhibitor, Copanlisib Given in Combination With the Immunotherapeutic Agents, Nivolumab and Rituximab in Patients With Relapsed/Refractory Indolent Lymphoma

NCT04431635 | Terminated Phase 1 DMC FDA Drug

• 3 other identifiers: UMCC 2019.097BTCRC-LYM17-145HUM00166647
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 5

Brief Summary

Patients with relapsed or refractory follicular or marginal zone lymphoma who have received at least one prior line of therapy will receive

• Copanlisib IV: day 1, 8, 15 every 28 days
• Nivolumab IV: Cycle 1 days 1 and 15; then day 1 only
• Rituximab IV: Cycle 1 days 1, 8, 15, 22; then day 1 (C2-6); then Q2 cycles (8-12)

Conditions

Indolent Lymphoma

Outcome Measures

Primary Outcomes (2)

• MTD (Maximum Tolerated Dose) of copanlisib given in combination with nivolumab and rituximab

  To estimate the MTD (Maximum Tolerated Dose) of copanlisib given in combination with nivolumab and rituximab

  28 days

• Complete Response rate of the combination of copanlisib, nivolumab, and rituximab given at the MTD.

  To estimate the Complete Response (CR) rate of the combination of copanlisib, nivolumab, and rituximab given at the MTD as determined by Lyric criteria \[Cheson 2016}

  1 year

Secondary Outcomes (5)

• Summarize Adverse Events

  Up to two years

• Overall Response

  1 year

• Duration of Response

  Up to two years

• Progression Free Survival

  Up to two years

• Time to Next Treatment

  Up to two years

Study Arms (1)

Arm A: Copanlisib, Nivolumab & Rituximab

EXPERIMENTAL

Copanlisib IV: day 1, 8, 15 every 28 days Nivolumab IV: Cycle 1 days 1 and 15; then day 1 only Rituximab IV: Cycle 1 days 1, 8, 15, 22; then day 1 (C2-6); then Q2 cycles (8-12)

Drug: Copanlisib; Drug: Nivolumab; Drug: Rituximab

Interventions

Copanlisib DRUG

Copanlisib IV: day 1, 8, 15 every 28 days

Arm A: Copanlisib, Nivolumab & Rituximab

Nivolumab DRUG

Nivolumab IV: Cycle 1 days 1 and 15; then day 1 only

Arm A: Copanlisib, Nivolumab & Rituximab

Rituximab DRUG

Rituximab IV: Cycle 1 days 1, 8, 15, 22; then day 1 (C2-6); then Q2 cycles (8-12)

Arm A: Copanlisib, Nivolumab & Rituximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years at the time of informed consent.
• Diagnosis of relapsed or refractory indolent follicular or marginal zone lymphoma established by histologic assessment by a hematopathologist that has relapsed after at least one line of chemo-immunotherapy.
• Immunohistochemistry of the biopsy or
• Flow cytometry of the biopsy
• ECOG Performance Status ≤ 2
• Has an indication for treatment based on the presence of symptoms and/or GELF criteria as referenced in appendix A.
• Must have failed or not be a candidate for an autologous stem cell transplantation.
• Women of childbearing potential must be willing to use appropriate contraception (barrier and hormonal therapy) or abstain from heterosexual activity from the point of registration through at least 12 months after the last dose of study drugs.
• \-- NOTE: Women of childbearing potential are those who have not been surgically sterilized, have not been free of menses for ≥ 1 year, or her sole male partner has had a vasectomy at least 6 months prior to screening.
• Male subjects capable of fathering a child who have a female partner of childbearing potential must agree to use appropriate method(s) of contraception or abstain from heterosexual activity starting with the first dose of study drug through 1 month after the last dose of the study drugs.
• Adequate organ function defined as
• Hepatic:
• Total Bilirubin ≤ 1.5 mg/dL
• AST and ALT ≤ 2.5 x ULN.
• Renal: Creatinine \< 2.0 mg/dl or CrCL \> 30 mL/minute

You may not qualify if:

• Pregnant or breastfeeding women. NOTE: Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to study registration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. NOTE: Breast milk cannot be stored for future use while the mother is being treated on study.
• Diagnosis of follicular grade 3b, post-transplant lymphoproliferative disorder (PTLD), or presence of histologic transformation.
• Primary or metastatic CNS disease prior to study enrollment
• Uncontrolled current illness, including, but not limited to ongoing or active infections, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmia, evidence of interstitial lung disease or active, noninfectious pneumonitis including symptomatic and/or pneumonitis requiring treatment and/or psychiatric illness or social situations that would limit compliance with study requirements.
• History of inflammatory bowel disease i.e. Crohn's disease, ulcerative colitis.
• HIV infection. NOTE: HIV testing is required.
• Active infection with Hepatitis B or C virus (defined as a positive Hepatitis B surface antigen/ positive Hepatitis C antibody or detectable viral load by PCR). Patients with positive antibody but negative viral loads will be eligible for study participation but will require appropriate prophylaxis.
• NOTE: Hepatitis B and C testing are required.
• Screening rate-corrected (using Friderica's correction) QT interval (QTcF) must not be \> 480 msec via a standard 12-lead ECG within 28 days prior to registration.
• Concomitant therapy in the last 4 weeks of any of the following: cytotoxic chemotherapy, immunosuppressive agents, other investigational therapies, or chronic use of systemic corticosteroids (doses ≤ 10 mg/day prednisone or equivalent are permitted).
• Active or prior documented autoimmune or inflammatory disorders within the past 3 years prior to study registration. The following are exceptions to this criterion:
• Subjects with vitiligo or alopecia
• Subjects with hypothyroidism (eg. following Hashimoto syndrome) stable on hormone replacement or psoriasis not requiring systemic treatment.
• Known allergy or reaction to any component of either study drug formulation.
• Prior allogeneic stem cell transplant.

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead
• Bayer: collaborator
• Bristol-Myers Squibb: collaborator
• University of Michigan: collaborator
• Big Ten Cancer Research Consortium: collaborator

Study Sites (5)

University of Illinois Cancer Center

Chicago, Illinois, 60612, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

MeSH Terms

Interventions

copanlisib; Nivolumab; Rituximab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Murine-Derived

Study Officials

• Yasmin H Karimi, MD

  The University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2020
• First Posted: June 16, 2020
• Study Start: June 15, 2020
• Primary Completion: November 14, 2023
• Study Completion: November 14, 2023
• Last Updated: September 27, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)