Palbociclib in Combination With Chemotherapy in Treating Children With Relapsed Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma (LL)

NCT03792256 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: AINV18P1NCI-2019-02774
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 19

Brief Summary

AINV18P1 is a Phase 1 study where palbociclib will be administrated in combination with a standard re-induction platform in pediatric relapsed Acute Lymphoblastic Leukemia (ALL) and lymphoblastic lymphoma (LL). LL patients are included because the patient population is rare and these patients are most commonly treated with ALL regimens. The proposed palbociclib starting dose for this study will be 50 mg/m\^2/day for 21 days.

Conditions

Leukemia, Lymphocytic; Lymphoblastic Lymphoma; T-cell Lymphoma; T-cell Leukemia; Recurrent Disease; Acute Leukemia

Outcome Measures

Primary Outcomes (7)

• Frequency of Dose Limiting Toxicities of Palbociclib

  The frequency (%) of patients experiencing a cycle 1 dose limiting toxicity at least possibly attributable to Palbociclib by study part and dose level.

  Up to 32 days

• Frequency of Adverse Events of Palbociclib

  The frequency (%) of patients experiencing adverse events at least possibly attributable to Palbociclib by study part and dose level.

  Up to 26 months

• Area Under the Drug Concentration Curve of Palbociclib

  The median (min, max) of the area under the drug concentration curve for Palbociclib determined by measures at 0, 1, 2, 4, 8, and 24 hours post-dose on day 11 by study part and dose level.

  Up to 11 days

• Half-life of Palbociclib

  The median (min, max) of the half-life of Palbociclib determined by measures at 0, 1, 2, 4, 8, and 24 hours post-dose on day 11 by study part and dose level.

  Up to 11 days

• Maximum Serum Concentration of Palbociclib

  Median (min, max) of the maximum serum concentration of Palbociclib determined by measures at 0, 1, 2, 4, 8, and 24 hours post-dose on day 11 by study part and dose level

  Up to 11 days

• Time to Reach Maximum Serum Concentration of Palbociclib

  Median (min, max) of the maximum time to reach serum concentration of Palbociclib determined by measures at 0, 1, 2, 4, 8, and 24 hours post-dose on day 11 by study part and dose level

  Up to 11 days

• Clearance of Palbociclib

  Median (min, max) of the clearance of Palbociclib determined by measures at 0, 1, 2, 4, 8, and 24 hours post-dose on day 11 by study part and dose level

  Up to 11 days

Secondary Outcomes (11)

• Number of Participants With at Least Partial Response to Palbociclib

  up to 26 months

• Absolute Peripheral Blast Count of Palbociclib

  Up to 3 days

• Radiographic Response of Palbociclib in Patients With LL Patients

  Day 32

• RB1 Expression of Palbociclib

  Up to 4 days

• Phospho-RB1 Expression of Palbociclib

  Up to 4 days

Study Arms (1)

Treatment (Palbociclib)

EXPERIMENTAL

Patients receive Palbociclib 50 mg/m\^2 (starting dose with maximum dose of 100 mg) PO (or via NG-tube) once daily on Days 1-21; Intrathecal cytarabine (IT ARAC) age-based dosing on Day 1, Doxorubicin 60 mg/m\^2 IV push or infusion over 1-15 min on Day 4; Prednisone or prednisolone 40 mg/m\^2 PO divided BID or TID on days 4-31; Vincristine 1.5 mg/m\^2 (maximum dose 2 mg) IV push or mini-bag per institutional policy on days 4, 11, 18, and 25; and Pegaspargase 2500 IU/m\^2 IV over 1-2 hours on Days 5, and 18. If CNS3 leukemia is present, patients receive Intrathecal Triple Therapy (ITT) age-based dosing on days 4, 11, 18, and 25. Patients known to be CNS3 at study entry may receive ITT on Day 1 rather than IT ARAC. If CNS1 and 2 leukemia present, patient receive Methotrexate (IT MTX) age-based dosing on Days 18 and 32. Treatment will be given for one cycle, 32 days, in the absence of disease progression or unacceptable toxicity.

Drug: Palbociclib; Drug: Cytarabine; Drug: Methotrexate; Drug: Hydrocortisone; Drug: Doxorubicin; Drug: Prednisolone; Drug: Vincristine; Drug: Pegaspargase; Drug: Prednisone

Interventions

Palbociclib DRUG

Given PO (or via NG- tube)

Treatment (Palbociclib)

Cytarabine DRUG

Given intrathecally (IT)

Treatment (Palbociclib)

Methotrexate DRUG

Given intrathecally (IT)

Treatment (Palbociclib)

Hydrocortisone DRUG

Given IT

Treatment (Palbociclib)

Doxorubicin DRUG

Given intravenously (IV)

Treatment (Palbociclib)

Prednisolone DRUG

Either prednisone or prednisolone is given PO

Treatment (Palbociclib)

Vincristine DRUG

Given IV

Treatment (Palbociclib)

Pegaspargase DRUG

Given IV

Treatment (Palbociclib)

Prednisone DRUG

Either prednisone or prednisolone is given PO

Treatment (Palbociclib)

Eligibility Criteria

• Age: 12 Months - 31 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients with recurrent or refractory B- or T-lineage lymphoblastic leukemia and lymphoma.
• Patients with leukemia must have ≥ 5% (M2 or M3) bone marrow blasts with or without an extramedullary site of relapse. Morphologic relapse for M2 should be confirmed using flow cytometry, FISH and/or cytogenetics or molecular techniques.
• Patients with LL must have either measurable or evaluable disease.
• Patients with first or greater relapsed T-lineage ALL or LL and second or greater relapsed B-lineage ALL or LL are eligible.
• Patients with primary refractory disease with at least 2 prior induction attempts or first relapse refractory to at least one prior re-induction attempt are eligible.
• Karnofsky \>= 50% for patients \> 16 years of age and Lansky \>= 50 for patients \<= 16 years of age.
• Note: Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately.
• Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive. See DVL homepage for commercial and Phase 1 investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment.
• A waiting period prior to enrollment is not required for patients receiving standard cytotoxic maintenance chemotherapy (i.e., corticosteroid, vincristine, 6MP, and/or methotrexate).
• Intrathecal cytotoxic therapy: No waiting period is required for patients having received intrathecal cytarabine, methotrexate, and/or hydrocortisone. Intrathecal chemotherapy given at the time of diagnostic LP to evaluate for relapse prior to study enrollment is allowed.
• At least 14 days must have elapsed after the completion of other cytotoxic therapy, with the exception of hydroxyurea, for patients not receiving standard maintenance therapy. Additionally, patients must have fully recovered from all acute toxic effects of prior therapy.
• NOTE: Cytoreduction with hydroxyurea in patients can be initiated and continued for up to 24 hours prior to the start of protocol therapy.
• Note: Intrathecal chemotherapy that is given up to 72 hours prior to initiation of systemic chemotherapy per AINV18P1 counts as protocol therapy and not prior anti-cancer therapy. Intrathecal chemotherapy given \> 72 hours prior does not count as protocol therapy.
• Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or ANC counts): \>= 7 days after the last dose of agent. See DVL homepage for commercial and Phase 1 investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment.

You may not qualify if:

• Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies. Based on the mechanism of action, palbociclib may be expected to cause fetal harm if used during pregnancy. Pregnancy tests must be obtained in girls who are post-menarche. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study therapy. Women of reproductive potential should use effective contraception during treatment and for at least 3 weeks after the last dose of palbociclib. Males with female partners of reproductive potential should use effective contraception during treatment and for 3 months after the last dose of palbociclib. Animal data suggests that palbociclib may affect male fertility.
• Prednisone or methylprednisolone for ≤ 120 hours (5 days) may be administered for cytoreduction up to 24 hours prior to the start of protocol therapy and as treatment for allergic reactions or for physiologic replacement/stress dosing of hydrocortisone for documented adrenal insufficiency. Corticosteroids are not allowed for other indications. If used to modify immune adverse events related to prior therapy, ≥ 14 days must have elapsed since last dose of corticosteroid.
• Patients who are currently receiving another investigational drug.
• Patients who are currently receiving other anti-cancer agents are not eligible \[except patients receiving hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy\].
• Patients who are currently receiving drugs that are strong inhibitors and/or inducers of CYP3A4 or sensitive CYP3A4 substrates and CYP3A4 substrates with a narrow therapeutic range are not eligible. Strong inducers or inhibitors of CYP3A4 are prohibited from 14 days prior to enrollment to the end of the study.
• Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant.
• Patients must be able to swallow intact capsules or liquid. Patients that are unable to swallow oral medications may receive palbociclib through an NG tube. G tube administration is not allowed.
• Patients who have an uncontrolled infection defined as below:
• Fever above 38.2°C within 48 hours of study enrollment with clinical signs of infection. Fever that is determined to be due to tumor burden is allowed if patients have documented negative blood cultures for at least 48 hours prior to enrollment and no concurrent signs or symptoms of active infection or hemodynamic instability.
• A positive fungal culture within 30 days of study enrollment or active therapy for presumed invasive fungal infection.
• Patients may be receiving IV or oral antibiotics to complete a course of therapy for a prior documented infection as long as cultures have been negative for at least 48 hours and signs or symptoms of active infection have resolved. For patients with c. difficile diarrhea, at least 72 hours of antibacterial therapy must have elapsed and stools must have normalized to baseline.
• Active viral or protozoal infection requiring IV treatment.
• Patients known to have one of the following concomitant genetic syndromes: Down syndrome, Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachmann syndrome or any other known bone marrow failure syndrome.
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study.
• Cumulative prior anthracycline exposure must not exceed 400 mg/m2 of DOXOrubicin equivalents

Sponsors & Collaborators

• Children's Oncology Group: lead

Study Sites (19)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

Location

Loma Linda University Medical Center

Loma Linda, California, 92354, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, 94304, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Children's Healthcare of Atlanta - Egleston

Atlanta, Georgia, 30322, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

C S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, 10016, United States

Location

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Saint Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Related Publications (1)

• Raetz EA, Teachey DT, Minard C, Liu X, Norris RE, Denic KZ, Reid J, Evensen NA, Gore L, Fox E, Loh ML, Weigel BJ, Carroll WL. Palbociclib in combination with chemotherapy in pediatric and young adult patients with relapsed/refractory acute lymphoblastic leukemia and lymphoma: A Children's Oncology Group study (AINV18P1). Pediatr Blood Cancer. 2023 Nov;70(11):e30609. doi: 10.1002/pbc.30609. Epub 2023 Aug 8.

  PMID: 37553297 DERIVED

MeSH Terms

Conditions

Leukemia, Lymphoid; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, T-Cell; Leukemia, T-Cell; Recurrence

Interventions

palbociclib; Cytarabine; Methotrexate; Hydrocortisone; Doxorubicin; Prednisolone; Vincristine; pegaspargase; Prednisone

Condition Hierarchy (Ancestors)

Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Lymphoma; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienetriols; Pregnadienes; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines; Pregnadienediols

Results Point of Contact

• Title: Results Reporting Coordinator
• Organization: Children's Oncology Group

resultsreportingcoordinator@childrensoncologygroup.org

16264470064

Study Officials

• Elizabeth Raetz, MD

  Children's Oncology Group

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: November 29, 2018
• First Posted: January 3, 2019
• Study Start: April 11, 2019
• Primary Completion: June 30, 2021
• Study Completion: September 30, 2023
• Last Updated: March 21, 2025
• Results First Posted: August 16, 2024

Record last verified: 2025-03

Locations

US (19)