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

Completed · Phase 1

Conditions studied: Leukemia, Lymphocytic, Lymphoblastic Lymphoma, T-cell Lymphoma, T-cell Leukemia, Recurrent Disease, Acute Leukemia

In brief

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.

Key facts

Study ID

NCT03792256

Run by

Children's Oncology Group

People needed

12

Starts

2019-04-11

Expected to finish

2023-09-30

Last updated by the study team

2025-03-21

Who can join

Age: 1 and older, up to 31. Sex: any. Healthy volunteers: not accepted.

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.
• NOTE: Cytoreduction with prednisone or methylprednisolone for <= 120 hours (5 days) in patients can be initiated and continued for up to 24 hours prior to the start of protocol therapy.
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody with the exception of blinatumomab, and toxicity related to prior antibody therapy must be recovered to Grade <= 1. Patients must have been off blinatumomab infusion for at least 14 days and all drug related toxicity must have resolved to Grade <= 1.
• Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid and toxicity related to prior immune therapy must be recovered to Grade <= 1 off corticosteroids.
• Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator.
• Interleukins, Interferons and Cytokines (other than Hematopoietic Growth Factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than Hematopoietic Growth Factors)
• Stem cell Infusions (with or without TBI):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including DLI or boost infusion: >= 84 days after infusion and no evidence of GVHD.
• Autologous stem cell infusion including boost infusion: >= 42 days.
• Cellular Therapy: >= 30 days after the completion of any type of cellular therapy (e.g. modified T cells, NK cells, dendritic cells, etc.)
• XRT/External Beam Irradiation including Protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial BM radiation.

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

Where it is running

• Children's Hospital of Alabama — Birmingham, Alabama, United States
• Loma Linda University Medical Center — Loma Linda, California, United States
• Children's Hospital of Orange County — Orange, California, United States
• Lucile Packard Children's Hospital Stanford University — Palo Alto, California, United States
• Children's Hospital Colorado — Aurora, Colorado, United States
• Children's National Medical Center — Washington D.C., District of Columbia, United States
• Children's Healthcare of Atlanta - Egleston — Atlanta, Georgia, United States
• Riley Hospital for Children — Indianapolis, Indiana, United States
• C S Mott Children's Hospital — Ann Arbor, Michigan, United States
• University of Minnesota/Masonic Cancer Center — Minneapolis, Minnesota, United States
• Laura and Isaac Perlmutter Cancer Center at NYU Langone — New York, New York, United States
• NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center — New York, New York, United States
• Cincinnati Children's Hospital Medical Center — Cincinnati, Ohio, United States
• University of Oklahoma Health Sciences Center — Oklahoma City, Oklahoma, United States
• Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States
• Children's Hospital of Pittsburgh of UPMC — Pittsburgh, Pennsylvania, United States
• Saint Jude Children's Research Hospital — Memphis, Tennessee, United States
• Primary Children's Hospital — Salt Lake City, Utah, United States
• Seattle Children's Hospital — Seattle, Washington, United States

Full record on ClinicalTrials.gov

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